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Yoo J, Kim Y, Back JH, Shin J, Bae PK, Park KM, Kim M, Seo YH, Bak Y, Heo YH, Heo J, Choi H, Kim Y, Lee S, Lee JE, Jeong S, Yang JK, Kim S. Surface-engineered nanobeads for regioselective antibody binding: A robust immunoassay platform leveraging catalytic signal amplification. Biosens Bioelectron 2025; 281:117463. [PMID: 40228457 DOI: 10.1016/j.bios.2025.117463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 03/03/2025] [Accepted: 04/07/2025] [Indexed: 04/16/2025]
Abstract
Regulating protein interactions and protein corona formation of nanomaterials is crucial for advancing nanomedicine, where surface engineering of nanomaterials plays a pivotal role in precise control over biological interactions. Here, we present a surface-engineered nanoparticle-based immunoassay platform using carboxyl-enriched polystyrene nanobeads (CEPS) with regioselectively controlled antibody-binding properties. Proteomic analysis and theoretical simulation revealed that CEPS has an enhanced Fc-specific binding affinity for immunoglobulins compared to conventional carboxylated polystyrene beads, with a higher surface carboxyl density critically mediating protein interactions. This regioselective antibody binding with unique Fc-specific affinity eliminates the need for complex surface modifications, streamlining the assay process and broadening the applicability across various immunoassay formats. Additionally, incorporating a palladium catalyst within CEPS enables solvent-triggered on-demand catalytic signal amplification using a leucodye substrate, providing a more stable alternative to enzyme-based methods while significantly enhancing detection sensitivity and stability. The platform demonstrated enhanced performance in detecting clinically relevant biomarkers, including C-reactive protein, interferon-gamma, and the receptor-binding domain of SARS-CoV2, achieving lower detection limits and faster response times compared to conventional enzyme-based ELISA systems. Notably, the CEPS-based assay retained catalytic activity for over 140 days at room temperature, underscoring its potential for reliable, long-term use in diverse diagnostic applications.
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Affiliation(s)
- Jounghyun Yoo
- Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
| | - Youngsun Kim
- Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
| | - Ji Hyun Back
- Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
| | - Jawon Shin
- Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
| | - Pan Kee Bae
- HGUARD Inc., Daejeon, 34054, Republic of Korea
| | - Kyung Mi Park
- BioNano Health Guard Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea
| | - Myung Kim
- Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
| | - Young Hun Seo
- Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea; Biosensor Group, Korea Institute of Science and Technology Europe, Campus E7.1, Saarbrücken, 66123, Germany
| | - Yecheol Bak
- Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
| | - Yoon Ho Heo
- Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
| | - Jeongyun Heo
- Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
| | - Honghwan Choi
- Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea
| | - Yongju Kim
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea
| | - Sangyoup Lee
- Bionic Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
| | - Ji Eun Lee
- Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.
| | - Sohdam Jeong
- Department of Chemical Engineering, Dong-Eui University, Busan, 47340, Republic of Korea.
| | - Jin-Kyoung Yang
- Department of Chemical Engineering, Dong-Eui University, Busan, 47340, Republic of Korea.
| | - Sehoon Kim
- Chemical and Biological Integrative Research Center, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea.
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Polo-Montalvo A, Gómez-Cerezo N, Cicuéndez M, González B, Izquierdo-Barba I, Arcos D. Osteogenic and Antibacterial Response of Levofloxacin-Loaded Mesoporous Nanoparticles Functionalized with N-Acetylcysteine. Pharmaceutics 2025; 17:519. [PMID: 40284514 PMCID: PMC12030205 DOI: 10.3390/pharmaceutics17040519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 04/01/2025] [Accepted: 04/11/2025] [Indexed: 04/29/2025] Open
Abstract
Background/Objectives: Bone infection is one of the most prevalent complications in orthopedic surgery. This pathology is mostly due to bacterial pathogens, among which S. aureus stands out. The formation of a bacterial biofilm makes systemic treatment with antibiotics ineffective. Herein we propose a nanosystem composed of mesoporous bioactive glass nanoparticles (MBGN) loaded with levofloxacin and functionalized with N-acetylcysteine (NAC), aiming to offer an alternative to current treatments. These nanoparticles would present antibacterial activity able to disintegrate the biofilm and regenerate the peri-implantar osseous tissue. Methods: MBGN of composition 82.5 SiO2-17.5 CaO have been synthesized, loaded with levofloxacin, and functionalized with NAC (MBGN-L-NAC). The antimicrobial activity against mature S. aureus biofilms and bioactivity of the nanosystem have been evaluated, as well as its biocompatibility and ability to promote murine pre-osteoblastic MC3T3-E1 differentiation. Results: MBGNs exhibited high surface areas and radial mesoporosity, allowing up to 23.1% (% w/w) of levofloxacin loading. NAC was covalently bound keeping the mucolytic thiol group, SH, available. NAC and levofloxacin combination enhances the activity against S. aureus by disrupting mature biofilm integrity. This nanosystem was biocompatible with pre-osteoblasts, enhanced their differentiation towards a mature osteoblast phenotype, and promoted bio-mimetic mineralization under in vitro conditions. MBGN-L-NAC nanoparticles induced greater osteogenic response of osteoprogenitor cells through increased alkaline phosphatase expression, increased mineralization, and stimulation of pre-osteoblast nodule formation. Conclusions: MBGN-L-NAC exhibits a more efficient antibacterial activity due to the biofilm disaggregation exerted by NAC, which also contributes to enhance the osteoinductive properties of MBGNs, providing a potential alternative to conventional strategies for the management of bone infections.
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Affiliation(s)
- Alberto Polo-Montalvo
- Departamento Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; (A.P.-M.); (N.G.-C.); (M.C.); (B.G.)
- Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
| | - Natividad Gómez-Cerezo
- Departamento Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; (A.P.-M.); (N.G.-C.); (M.C.); (B.G.)
- Instituto de Investigación Sanitaria, Hospital 12 de Octubre i+12, 28040 Madrid, Spain
| | - Mónica Cicuéndez
- Departamento Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; (A.P.-M.); (N.G.-C.); (M.C.); (B.G.)
- Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
| | - Blanca González
- Departamento Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; (A.P.-M.); (N.G.-C.); (M.C.); (B.G.)
- Instituto de Investigación Sanitaria, Hospital 12 de Octubre i+12, 28040 Madrid, Spain
- CIBER de Bioingeniería, Biomateriales y Nanomedicina—CIBER-BBN, 28040 Madrid, Spain
| | - Isabel Izquierdo-Barba
- Departamento Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; (A.P.-M.); (N.G.-C.); (M.C.); (B.G.)
- Instituto de Investigación Sanitaria, Hospital 12 de Octubre i+12, 28040 Madrid, Spain
- CIBER de Bioingeniería, Biomateriales y Nanomedicina—CIBER-BBN, 28040 Madrid, Spain
| | - Daniel Arcos
- Departamento Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; (A.P.-M.); (N.G.-C.); (M.C.); (B.G.)
- Instituto de Investigación Sanitaria, Hospital 12 de Octubre i+12, 28040 Madrid, Spain
- CIBER de Bioingeniería, Biomateriales y Nanomedicina—CIBER-BBN, 28040 Madrid, Spain
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Adhikari A, Chen IA. Antibody-Nanoparticle Conjugates in Therapy: Combining the Best of Two Worlds. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025; 21:e2409635. [PMID: 40051146 PMCID: PMC12001320 DOI: 10.1002/smll.202409635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 01/02/2025] [Indexed: 04/17/2025]
Abstract
Monoclonal antibodies (mAbs) and antibody fragments have revolutionized medicine as highly specific binding agents and inhibitors. At the same time, several types of nanomaterials, including liposomes, lipid nanoparticles (NPs), polymersomes, metal and metal oxide NPs, and protein nanostructures, are increasingly utilized and explored for therapeutic potential due to their versatility, chemical and physical properties, and tunability. However, nanomaterials alone often lack specificity, leading to relatively low efficacy and/or high toxicity. To address this problem, a rapidly emerging area is antibody-nanomaterial conjugates (ANCs), which combine the precise targeting specificity of antibodies with the effector functionality of the nanomaterial. In this review, we give a brief introduction to mAbs and major conjugation techniques, describe major classes of nanomaterials being studied for therapeutic potential, and review the literature on ANCs of each class. Special focus is given to emerging applications including ANCs addressing the blood-brain barrier, ANCs delivering nucleic acids, and light-activated ANCs. While many disease targets are related to cancer, ANCs are also under development to address autoimmune, neurological, and infectious diseases. While important challenges remain, ANCs are poised to become a next-generation therapeutic technology.
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Affiliation(s)
- Aniruddha Adhikari
- Department of Chemical and Biomolecular EngineeringDepartment of Chemistry and BiochemistryUniversity of CaliforniaLos AngelesCA90049USA
| | - Irene A. Chen
- Department of Chemical and Biomolecular EngineeringDepartment of Chemistry and BiochemistryUniversity of CaliforniaLos AngelesCA90049USA
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K M N, Karmakar S, Sahoo B, Mishrra N, Moitra P. Use of Quantum Dots as Nanotheranostic Agents: Emerging Applications in Rare Genetic Diseases. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025; 21:e2407353. [PMID: 39828615 DOI: 10.1002/smll.202407353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 01/03/2025] [Indexed: 01/22/2025]
Abstract
Rare genetic diseases (RGDs) affect a small percentage of the global population but collectively have a substantial impact due to their diverse manifestations. Although the precise reasons behind these diseases remain unclear, roughly 80% of cases are genetically linked. Recent efforts focus on understanding pathology and developing new diagnostic and therapeutic approaches for RGDs. However, there persists a gap between fundamental research and clinical therapeutic approaches, where advancements in nanotechnology offer promising improvements. In this context, nanosized light-emitting quantum dots (QDs), ranging from 2-10 nm, are promising materials for diverse applications. Their size-tunable light emission, high quantum yield, and photostability allow for precise tracking of cargo. Additionally, QDs can be functionalized with therapeutic agents, antibodies, or peptides to target specific cellular pathways, enhancing treatment efficacy while minimizing side effects. By combining diagnostic and therapeutic capabilities in a single platform, QDs thus offer a versatile and powerful approach to tackle rare genetic disorders. Despite several reviews on various therapeutic applications of QDs, their utilization in the specific domain of RGDs is not well documented. This review highlight QDs' potential in diagnosing and treating certain RGDs and addresses the challenges limiting their application.
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Affiliation(s)
- Neethu K M
- Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Berhampur, Berhampur, Odisha, 760010, India
| | - Shyamal Karmakar
- Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Berhampur, Berhampur, Odisha, 760010, India
| | - Baishakhi Sahoo
- Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Berhampur, Berhampur, Odisha, 760010, India
| | - Navniet Mishrra
- Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Berhampur, Berhampur, Odisha, 760010, India
| | - Parikshit Moitra
- Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Berhampur, Berhampur, Odisha, 760010, India
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5
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Handak EM, Amin DH, Elhateir MM. Design and assessment of lipase-CuO nanoparticle conjugates for enhanced antimicrobial efficacy against clinical pathogens. BMC Biotechnol 2025; 25:16. [PMID: 39920647 PMCID: PMC11806700 DOI: 10.1186/s12896-025-00950-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 01/24/2025] [Indexed: 02/09/2025] Open
Abstract
In the battle against clinical infections particularly the resistant pathogens, the creation of new antimicrobial drugs is essential. This study focuses on synthesis and characterization of Lipase-CuO nanoparticle conjugates in order to investigate their antibacterial efficiency. Lipase enzyme and CuO nanoparticles were synthesized biologically by specific selected fungal strains. Statistical optimization of lipase enzyme was done using a Plackett-Burman design giving two enhancement models for lipase production with increasing in productivity up to 143.43% (2800 U/ml). Copper oxide (CuO) nanoparticles were characterized using visual indication of greenish color formation, UV-vis spectrum analysis which revealed a strong peak at 300 nm. Also, CuO nanoparticles appeared as distinct, well-dispersed spherical particles with average size of 71.035 nm using TEM, while conjugate appears as large protein molecules linked to the nanoparticles. Also, using techniques like energy dispersive X-ray (EDAX) the resultant conjugates formation was confirmed as the elemental analysis approved its formation. The antimicrobial activity of Lipase-CuO nanoparticles conjugates was tested against a range of clinical pathogens. The results demonstrated a significant increase in antimicrobial potency compared to both CuO nanoparticles and lipase alone particularly against E. coli strain NRC B-3703 with remarkable increase of 373.6% and 75% followed by S. aureus with increase of 50 and 42.8%compared to that of individual CuO nanoparticles and lipase enzyme, respectively. These findings suggest that Lipase-CuO nanoparticle conjugates hold great promise as a novel antimicrobial strategy, offering a potential solution to combat bacterial infections, especially those caused by multidrug-resistant strains. The study highlights the importance of nanotechnology in enhancing the efficacy of traditional antimicrobial agents and opens new avenues for targeted antimicrobial therapies.
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Affiliation(s)
- Eman M Handak
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University (Girls Branch), Cairo, 11754, Egypt
| | - Dina H Amin
- Microbiology Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
| | - Mai M Elhateir
- Botany and Microbiology Department, Faculty of Science, Al-Azhar University (Girls Branch), Cairo, 11754, Egypt
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Zhang R, Guo Y, Huang C, Fang J. Label-Free SERS Analysis of Biological and Physical Information Heterogeneity of Nanoscale Extracellular Vesicle by Matching Specific Sizes of Enhanced Particles. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2025; 21:e2409806. [PMID: 39726305 DOI: 10.1002/smll.202409806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 12/02/2024] [Indexed: 12/28/2024]
Abstract
The heterogeneity of extracellular vesicles (EVs) surface information represents different functions, which is neglected in previous studies. In this study, a label-free SERS analysis approach is demonstrated to study fundamental EV biological and physical information heterogeneity by matching specific sizes of nano-enhanced particles. This strategy reveals informative, comprehensive, and high-quality SERS spectra of the overall exosome surface, and effectively circumvents the key information loss caused by the spatial resistance of NPs binding to the 293 exosomes' concave structure. The classification of normal and cancerous cell-derived exosomes by PCA method, the accuracy is improved from 91.2% to 95.1% by optimizing sizes of nano-enhanced particles. In addition, stem cell-derived EVs of diverse sizes and morphologies similarly show acuity of spectrum variation to NPs size, which is conductive to qualitative studies. This new strategy will offer a widened in-depth understanding of the surface information, size, and morphology of EVs, which can be applied to the study of biological functions.
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Affiliation(s)
- Ruiyuan Zhang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China
| | - Yu Guo
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China
| | - Chen Huang
- Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China
| | - Jixiang Fang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China
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Abedi A, Moosazadeh Moghaddam M, Kachuei R, Imani Fooladi AA. Exosomes as a Therapeutic Strategy in Cancer: Potential Roles as Drug Carriers and Immune Modulators. Biochim Biophys Acta Rev Cancer 2025; 1880:189238. [PMID: 39674417 DOI: 10.1016/j.bbcan.2024.189238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 12/04/2024] [Accepted: 12/05/2024] [Indexed: 12/16/2024]
Abstract
Exosome-based cancer immunotherapy is advancing quickly on the concept of artificially activating the immune system to combat cancer. They can mechanistically change the tumor microenvironment, increase immune responses, and function as efficient drug delivery vehicles because of their inherent bioactivity, low toxicity, and immunogenicity. Accurate identification of the mechanisms of action of exosomes in tumor environments, along with optimization of their isolation, purification, and characterization methods, is necessary to increase clinical applications. Exosomes can be modified through cargo loading and surface modification to enhance their therapeutic applications, either before or after the donor cells' isolation. These engineered exosomes can directly target tumor cells at the tumor site or indirectly activate innate and adaptive immune responses in the tumor microenvironment. This approach is particularly effective when combined with traditional cancer immunotherapy techniques such as vaccines, immune checkpoints, and CAR-T cells. It can improve anti-tumor responses, induce long-term immunity, and address the limitations of traditional therapies, such as poor penetration in solid tumors and immunosuppressive environments. This review aims to provide a comprehensive and detailed overview of the direct role of engineered exosomes as drug delivery systems and their immunomodulatory effects on tumors as an indirect approach to fighting cancer. Additionally, it will discuss novel immunotherapy options.
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Affiliation(s)
- Azam Abedi
- Tissue Engineering and Regenerative Medicine Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mehrdad Moosazadeh Moghaddam
- Tissue Engineering and Regenerative Medicine Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Reza Kachuei
- Molecular Biology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Abbas Ali Imani Fooladi
- Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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8
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Liu L, Pan Y, Ye L, Liang C, Mou X, Dong X, Cai Y. Optical functional nanomaterials for cancer photoimmunotherapy. Coord Chem Rev 2024; 517:216006. [DOI: 10.1016/j.ccr.2024.216006] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Ramimoghadam D, Eyckens DJ, Evans RA, Moad G, Holmes S, Simons R. Towards Sustainable Materials: A Review of Acylhydrazone Chemistry for Reversible Polymers. Chemistry 2024; 30:e202401728. [PMID: 38888459 DOI: 10.1002/chem.202401728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 06/07/2024] [Accepted: 06/17/2024] [Indexed: 06/20/2024]
Abstract
Transitioning towards a circular economy, extensive research has focused on dynamic covalent bonds (DCBs) to pave the way for more sustainable materials. These bonds enable debonding and rebonding on demand, as well as facilitating end-of-life recycling. Acylhydrazone/hydrazone chemistry offers a material with high stability under neutral and basic conditions making it a promising candidate for materials research, though the material is susceptible to acid degradation. However, this degradation under acidic conditions can be exploited, making it widely applicable in self-healing and biomedical fields, with potential for reprocessing and recycling. This review highlights studies exploring the reversibility of acylhydrazone/hydrazone bonds in various polymers, altering their properties, and utilizing them in applications such as self-healing, reprocessing, and recycling. The review also focuses on how the mechanical properties are affected by the presence of dynamic linkages, and methods to improve the mechanical performance.
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Affiliation(s)
- Donya Ramimoghadam
- Manufacturing, Commonwealth Scientific and Industrial Research Organization (CSIRO), Clayton, Victoria, 3168, Australia
| | - Daniel J Eyckens
- Manufacturing, Commonwealth Scientific and Industrial Research Organization (CSIRO), Clayton, Victoria, 3168, Australia
| | - Richard A Evans
- Manufacturing, Commonwealth Scientific and Industrial Research Organization (CSIRO), Clayton, Victoria, 3168, Australia
| | - Graeme Moad
- Manufacturing, Commonwealth Scientific and Industrial Research Organization (CSIRO), Clayton, Victoria, 3168, Australia
| | - Susan Holmes
- Manufacturing, Commonwealth Scientific and Industrial Research Organization (CSIRO), Clayton, Victoria, 3168, Australia
| | - Ranya Simons
- Manufacturing, Commonwealth Scientific and Industrial Research Organization (CSIRO), Clayton, Victoria, 3168, Australia
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Zhang Y, Lei F, Qian W, Zhang C, Wang Q, Liu C, Ji H, Liu Z, Wang F. Designing intelligent bioorthogonal nanozymes: Recent advances of stimuli-responsive catalytic systems for biomedical applications. J Control Release 2024; 373:929-951. [PMID: 39097195 DOI: 10.1016/j.jconrel.2024.07.073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 07/28/2024] [Accepted: 07/29/2024] [Indexed: 08/05/2024]
Abstract
Bioorthogonal nanozymes have emerged as a potent tool in biomedicine due to their unique ability to perform enzymatic reactions that do not interfere with native biochemical processes. The integration of stimuli-responsive mechanisms into these nanozymes has further expanded their potential, allowing for controlled activation and targeted delivery. As such, intelligent bioorthogonal nanozymes have received more and more attention in developing therapeutic approaches. This review provides a comprehensive overview of the recent advances in the development and application of stimuli-responsive bioorthogonal nanozymes. By summarizing the design outlines for anchoring bioorthogonal nanozymes with stimuli-responsive capability, this review seeks to offer valuable insights and guidance for the rational design of these remarkable materials. This review highlights the significant progress made in this exciting field with different types of stimuli and the various applications. Additionally, it also examines the current challenges and limitations in the design, synthesis, and application of these systems, and proposes potential solutions and research directions. This review aims to stimulate further research toward the development of more efficient and versatile stimuli-responsive bioorthogonal nanozymes for biomedical applications.
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Affiliation(s)
- Yan Zhang
- Institute of Special Environmental Medicine, Nantong University, Nantong 226019, China
| | - Fang Lei
- School of Public Health, Nantong University, Nantong 226019, China
| | - Wanlong Qian
- Institute of Special Environmental Medicine, Nantong University, Nantong 226019, China
| | - Chengfeng Zhang
- Institute of Special Environmental Medicine, Nantong University, Nantong 226019, China
| | - Qi Wang
- School of Public Health, Nantong University, Nantong 226019, China
| | - Chaoqun Liu
- School of Pharmacy, Henan University, Kaifeng 475004, China
| | - Haiwei Ji
- School of Public Health, Nantong University, Nantong 226019, China
| | - Zhengwei Liu
- Precision Immunology Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York 10029, USA.
| | - Faming Wang
- School of Public Health, Nantong University, Nantong 226019, China.
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11
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Hooe SL, Green CM, Susumu K, Stewart MH, Breger JC, Medintz IL. Optimizing the conversion of phosphoenolpyruvate to lactate by enzymatic channeling with mixed nanoparticle display. CELL REPORTS METHODS 2024; 4:100764. [PMID: 38714198 PMCID: PMC11133815 DOI: 10.1016/j.crmeth.2024.100764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Revised: 02/19/2024] [Accepted: 04/12/2024] [Indexed: 05/09/2024]
Abstract
Co-assembling enzymes with nanoparticles (NPs) into nanoclusters allows them to access channeling, a highly efficient form of multienzyme catalysis. Using pyruvate kinase (PykA) and lactate dehydrogenase (LDH) to convert phosphoenolpyruvic acid to lactic acid with semiconductor quantum dots (QDs) confirms how enzyme cluster formation dictates the rate of coupled catalytic flux (kflux) across a series of differentially sized/shaped QDs and 2D nanoplatelets (NPLs). Enzyme kinetics and coupled flux were used to demonstrate that by mixing different NP systems into clusters, a >10× improvement in kflux is observed relative to free enzymes, which is also ≥2× greater than enhancement on individual NPs. Cluster formation was characterized with gel electrophoresis and transmission electron microscopy (TEM) imaging. The generalizability of this mixed-NP approach to improving flux is confirmed by application to a seven-enzyme system. This represents a powerful approach for accessing channeling with almost any choice of enzymes constituting a multienzyme cascade.
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Affiliation(s)
- Shelby L Hooe
- Center for Bio/Molecular Science and Engineering Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375, USA
| | - Christopher M Green
- Center for Bio/Molecular Science and Engineering Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375, USA
| | - Kimihiro Susumu
- Optical Sciences Division Code 5611, U.S. Naval Research Laboratory, Washington, DC 20375, USA
| | - Michael H Stewart
- Optical Sciences Division Code 5611, U.S. Naval Research Laboratory, Washington, DC 20375, USA
| | - Joyce C Breger
- Center for Bio/Molecular Science and Engineering Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375, USA
| | - Igor L Medintz
- Center for Bio/Molecular Science and Engineering Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375, USA.
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12
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Sinsinbar G, Bindra AK, Liu S, Chia TW, Yoong Eng EC, Loo SY, Lam JH, Schultheis K, Nallani M. Amphiphilic Block Copolymer Nanostructures as a Tunable Delivery Platform: Perspective and Framework for the Future Drug Product Development. Biomacromolecules 2024; 25:541-563. [PMID: 38240244 DOI: 10.1021/acs.biomac.3c00858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/13/2024]
Abstract
Nanoformulation of active payloads or pharmaceutical ingredients (APIs) has always been an area of interest to achieve targeted, sustained, and efficacious delivery. Various delivery platforms have been explored, but loading and delivery of APIs have been challenging because of the chemical and structural properties of these molecules. Polymersomes made from amphiphilic block copolymers (ABCPs) have shown enormous promise as a tunable API delivery platform and confer multifold advantages over lipid-based systems. For example, a COVID booster vaccine comprising polymersomes encapsulating spike protein (ACM-001) has recently completed a Phase I clinical trial and provides a case for developing safe drug products based on ABCP delivery platforms. However, several limitations need to be resolved before they can reach their full potential. In this Perspective, we would like to highlight such aspects requiring further development for translating an ABCP-based delivery platform from a proof of concept to a viable commercial product.
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Affiliation(s)
- Gaurav Sinsinbar
- ACM Biolabs Pte Ltd., 71 Nanyang Drive, #02M-02, NTU Innovation Center, Singapore 638075, Singapore
| | - Anivind Kaur Bindra
- ACM Biolabs Pte Ltd., 71 Nanyang Drive, #02M-02, NTU Innovation Center, Singapore 638075, Singapore
| | - Shaoqiong Liu
- ACM Biolabs Pte Ltd., 71 Nanyang Drive, #02M-02, NTU Innovation Center, Singapore 638075, Singapore
| | - Teck Wan Chia
- ACM Biolabs Pte Ltd., 71 Nanyang Drive, #02M-02, NTU Innovation Center, Singapore 638075, Singapore
| | - Eunice Chia Yoong Eng
- ACM Biolabs Pte Ltd., 71 Nanyang Drive, #02M-02, NTU Innovation Center, Singapore 638075, Singapore
| | - Ser Yue Loo
- ACM Biolabs Pte Ltd., 71 Nanyang Drive, #02M-02, NTU Innovation Center, Singapore 638075, Singapore
| | - Jian Hang Lam
- ACM Biolabs Pte Ltd., 71 Nanyang Drive, #02M-02, NTU Innovation Center, Singapore 638075, Singapore
| | - Katherine Schultheis
- ACM Biolabs Pte Ltd., 71 Nanyang Drive, #02M-02, NTU Innovation Center, Singapore 638075, Singapore
| | - Madhavan Nallani
- ACM Biolabs Pte Ltd., 71 Nanyang Drive, #02M-02, NTU Innovation Center, Singapore 638075, Singapore
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13
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Jung I, Shin S, Baek MC, Yea K. Modification of immune cell-derived exosomes for enhanced cancer immunotherapy: current advances and therapeutic applications. Exp Mol Med 2024; 56:19-31. [PMID: 38172594 PMCID: PMC10834411 DOI: 10.1038/s12276-023-01132-8] [Citation(s) in RCA: 30] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 10/05/2023] [Indexed: 01/05/2024] Open
Abstract
Cancer immunotherapy has revolutionized the approach to cancer treatment of malignant tumors by harnessing the body's immune system to selectively target cancer cells. Despite remarkable advances, there are still challenges in achieving successful clinical responses. Recent evidence suggests that immune cell-derived exosomes modulate the immune system to generate effective antitumor immune responses, making them a cutting-edge therapeutic strategy. However, natural exosomes are limited in clinical application due to their low drug delivery efficiency and insufficient antitumor capacity. Technological advancements have allowed exosome modifications to magnify their intrinsic functions, load different therapeutic cargoes, and preferentially target tumor sites. These engineered exosomes exert potent antitumor effects and have great potential for cancer immunotherapy. In this review, we describe ingenious modification strategies to attain the desired performance. Moreover, we systematically summarize the tumor-controlling properties of engineered immune cell-derived exosomes in innate and adaptive immunity. Collectively, this review provides a comprehensive and intuitive guide for harnessing the potential of modified immune cell-derived exosome-based approaches, offering valuable strategies to enhance and optimize cancer immunotherapy.
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Affiliation(s)
- Inseong Jung
- Department of New Biology, DGIST, Daegu, 42988, Republic of Korea
| | - Sanghee Shin
- Department of New Biology, DGIST, Daegu, 42988, Republic of Korea
| | - Moon-Chang Baek
- Department of Molecular Medicine, CMRI, Exosome Convergence Research Center (ECRC), School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.
| | - Kyungmoo Yea
- Department of New Biology, DGIST, Daegu, 42988, Republic of Korea.
- New Biology Research Center, DGIST, Daegu, 43024, Republic of Korea.
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14
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Hooe SL, Smith AD, Dean SN, Breger JC, Ellis GA, Medintz IL. Multienzymatic Cascades and Nanomaterial Scaffolding-A Potential Way Forward for the Efficient Biosynthesis of Novel Chemical Products. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2309963. [PMID: 37944537 DOI: 10.1002/adma.202309963] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 10/25/2023] [Indexed: 11/12/2023]
Abstract
Synthetic biology is touted as the next industrial revolution as it promises access to greener biocatalytic syntheses to replace many industrial organic chemistries. Here, it is shown to what synthetic biology can offer in the form of multienzyme cascades for the synthesis of the most basic of new materials-chemicals, including especially designer chemical products and their analogs. Since achieving this is predicated on dramatically expanding the chemical space that enzymes access, such chemistry will probably be undertaken in cell-free or minimalist formats to overcome the inherent toxicity of non-natural substrates to living cells. Laying out relevant aspects that need to be considered in the design of multi-enzymatic cascades for these purposes is begun. Representative multienzymatic cascades are critically reviewed, which have been specifically developed for the synthesis of compounds that have either been made only by traditional organic synthesis along with those cascades utilized for novel compound syntheses. Lastly, an overview of strategies that look toward exploiting bio/nanomaterials for accessing channeling and other nanoscale materials phenomena in vitro to direct novel enzymatic biosynthesis and improve catalytic efficiency is provided. Finally, a perspective on what is needed for this field to develop in the short and long term is presented.
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Affiliation(s)
- Shelby L Hooe
- Center for Bio/Molecular Science and Engineering Code 6900, U.S. Naval Research Laboratory, Washington, DC, 20375, USA
- National Research Council, Washington, DC, 20001, USA
| | - Aaron D Smith
- Center for Bio/Molecular Science and Engineering Code 6900, U.S. Naval Research Laboratory, Washington, DC, 20375, USA
| | - Scott N Dean
- Center for Bio/Molecular Science and Engineering Code 6900, U.S. Naval Research Laboratory, Washington, DC, 20375, USA
| | - Joyce C Breger
- Center for Bio/Molecular Science and Engineering Code 6900, U.S. Naval Research Laboratory, Washington, DC, 20375, USA
| | - Gregory A Ellis
- Center for Bio/Molecular Science and Engineering Code 6900, U.S. Naval Research Laboratory, Washington, DC, 20375, USA
| | - Igor L Medintz
- Center for Bio/Molecular Science and Engineering Code 6900, U.S. Naval Research Laboratory, Washington, DC, 20375, USA
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15
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Bisht T, Adhikari A, Patil S, Dhoundiyal S. Bioconjugation Techniques for Enhancing Stability and Targeting Efficiency of Protein and Peptide Therapeutics. Curr Protein Pept Sci 2024; 25:226-243. [PMID: 37921168 DOI: 10.2174/0113892037268777231013154850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 09/05/2023] [Accepted: 09/15/2023] [Indexed: 11/04/2023]
Abstract
Bioconjugation techniques have emerged as powerful tools for enhancing the stability and targeting efficiency of protein and peptide therapeutics. This review provides a comprehensive analysis of the various bioconjugation strategies employed in the field. The introduction highlights the significance of bioconjugation techniques in addressing stability and targeting challenges associated with protein and peptide-based drugs. Chemical and enzymatic bioconjugation methods are discussed, along with crosslinking strategies for covalent attachment and site-specific conjugation approaches. The role of bioconjugation in improving stability profiles is explored, showcasing case studies that demonstrate successful stability enhancement. Furthermore, bioconjugation techniques for ligand attachment and targeting are presented, accompanied by examples of targeted protein and peptide therapeutics. The review also covers bioconjugation approaches for prolonging circulation and controlled release, focusing on strategies to extend half-life, reduce clearance, and design-controlled release systems. Analytical characterization techniques for bioconjugates, including the evaluation of conjugation efficiency, stability, and assessment of biological activity and targeting efficiency, are thoroughly examined. In vivo considerations and clinical applications of bioconjugated protein and peptide therapeutics, including pharmacokinetic and pharmacodynamic considerations, as well as preclinical and clinical developments, are discussed. Finally, the review concludes with an overview of future perspectives, emphasizing the potential for novel conjugation methods and advanced targeting strategies to further enhance the stability and targeting efficiency of protein and peptide therapeutics.
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Affiliation(s)
- Tanuja Bisht
- Department of Pharmacy, Shree Dev Bhoomi Institute of Education, Science and Technology, Veer Madho Singh Bhandari Uttarakhand Technical University, Dehradun, Uttarakhand, India
| | - Anupriya Adhikari
- Department of Pharmacy, Shree Dev Bhoomi Institute of Education, Science and Technology, Veer Madho Singh Bhandari Uttarakhand Technical University, Dehradun, Uttarakhand, India
| | - Shivanand Patil
- Department of Pharmacy, Shree Dev Bhoomi Institute of Education, Science and Technology, Veer Madho Singh Bhandari Uttarakhand Technical University, Dehradun, Uttarakhand, India
| | - Shivang Dhoundiyal
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
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16
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Rogers KE, Nag OK, Stewart MH, Susumu K, Oh E, Delehanty JB. Multivalent Display of Erythropoietin on Quantum Dots Enhances Aquaporin-4 Expression and Water Transport in Human Astrocytes In Vitro. Bioconjug Chem 2023; 34:2205-2214. [PMID: 38032892 DOI: 10.1021/acs.bioconjchem.3c00358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2023]
Abstract
In mammalian cells, growth factor-induced intracellular signaling and protein synthesis play a critical role in cellular physiology and homeostasis. In the brain's glymphatic system (GS), the water-conducting activity of aquaporin-4 (AQPN-4) membrane channels (expressed in polarized fashion on astrocyte end-feet) mediates the clearance of wastes through the convective transport of fluid and solutes through the perivascular space. The glycoprotein erythropoietin (EPO) has been shown to induce the astrocyte expression of AQPN-4 via signaling through the EPO receptor and the JAK/STAT signaling pathway. Here, we self-assemble EPO in a multivalent fashion onto the surface of semiconductor quantum dots (QDs) (driven by polyhistidine-based self-assembly) to drive the interaction of the bioconjugates with EPOR on human astrocytes (HA). This results in a 2-fold augmentation of JAK/STAT signaling activity and a 1.8-fold enhancement in the expression of AQPN-4 in cultured primary HA compared to free EPO. This translates into a 2-fold increase in the water transport rate in HA cells as measured by the calcein AM water transport assay. Importantly, EPO-QD-induced augmented AQPN-4 expression does not elicit any deleterious effect on the astrocyte viability. We discuss our results in the context of the implications of EPO-nanoparticle (NP) bioconjugates for use as research tools to understand the GS and their potential as therapeutics for the modulation of GS function. More generally, our results illustrate the utility of NP bioconjugates for the controlled modulation of growth factor-induced intracellular signaling.
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Affiliation(s)
- Katherine E Rogers
- Center for Bio/Molecular Science and Engineering, U.S. Naval Research Laboratory, Washington, District of Columbia 20375, United States
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland 20742, United States
| | - Okhil K Nag
- Center for Bio/Molecular Science and Engineering, U.S. Naval Research Laboratory, Washington, District of Columbia 20375, United States
| | - Michael H Stewart
- Optical Sciences Division, U.S. Naval Research Laboratory, Washington, District of Columbia 20375, United States
| | - Kimihiro Susumu
- Optical Sciences Division, U.S. Naval Research Laboratory, Washington, District of Columbia 20375, United States
| | - Eunkeu Oh
- Optical Sciences Division, U.S. Naval Research Laboratory, Washington, District of Columbia 20375, United States
| | - James B Delehanty
- Center for Bio/Molecular Science and Engineering, U.S. Naval Research Laboratory, Washington, District of Columbia 20375, United States
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17
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Hernández-López L, von Baeckmann C, Martínez-Esaín J, Cortés-Martínez A, Faraudo J, Caules C, Parella T, Maspoch D, Carné-Sánchez A. (Bio)Functionalisation of Metal-Organic Polyhedra by Using Click Chemistry. Chemistry 2023; 29:e202301945. [PMID: 37523177 DOI: 10.1002/chem.202301945] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 07/24/2023] [Accepted: 07/30/2023] [Indexed: 08/01/2023]
Abstract
The surface chemistry of Metal-Organic Polyhedra (MOPs) is crucial to their physicochemical properties because it governs how they interact with external substances such as solvents, synthetic organic molecules, metal ions, and even biomolecules. Consequently, the advancement of synthetic methods that facilitate the incorporation of diverse functional groups onto MOP surfaces will significantly broaden the range of properties and potential applications for MOPs. This study describes the use of copper(I)-catalysed, azide-alkyne cycloaddition (CuAAC) click reactions to post-synthetically modify the surface of alkyne-functionalised cuboctahedral MOPs. To this end, a novel Rh(II)-based MOP with 24 available surface alkyne groups was synthesised. Each of the 24 alkyne groups on the surface of the "clickable" Rh-MOP can react with azide-containing molecules at room temperature, without compromising the integrity of the MOP. The wide substrate catalogue and orthogonal nature of CuAAC click chemistry was exploited to densely functionalise MOPs with diverse functional groups, including polymers, carboxylic and phosphonic acids, and even biotin moieties, which retained their recognition capabilities once anchored onto the surface of the MOP.
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Affiliation(s)
- Laura Hernández-López
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, 08193, Barcelona, Spain
- Departament de Química, Facultat de Ciencies, Universitat Autonoma de Barcelona, 08193, Bellaterra, Spain
| | - Cornelia von Baeckmann
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, 08193, Barcelona, Spain
- Departament de Química, Facultat de Ciencies, Universitat Autonoma de Barcelona, 08193, Bellaterra, Spain
| | - Jordi Martínez-Esaín
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, 08193, Barcelona, Spain
| | - Alba Cortés-Martínez
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, 08193, Barcelona, Spain
- Departament de Química, Facultat de Ciencies, Universitat Autonoma de Barcelona, 08193, Bellaterra, Spain
| | - Jordi Faraudo
- Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), 08193, Bellaterra, Spain
| | - Caterina Caules
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, 08193, Barcelona, Spain
- Departament de Química, Facultat de Ciencies, Universitat Autonoma de Barcelona, 08193, Bellaterra, Spain
| | - Teodor Parella
- Servei de Ressonància Magnètica Nuclear, Universitat Autònoma de Barcelona, Campus UAB, Bellaterra, 08193, Barcelona, Spain
| | - Daniel Maspoch
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, 08193, Barcelona, Spain
- Departament de Química, Facultat de Ciencies, Universitat Autonoma de Barcelona, 08193, Bellaterra, Spain
- ICREA, Pg. Lluís Companys 23, 08010, Barcelona, Spain
| | - Arnau Carné-Sánchez
- Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, 08193, Barcelona, Spain
- Departament de Química, Facultat de Ciencies, Universitat Autonoma de Barcelona, 08193, Bellaterra, Spain
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18
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Scholtz L, Tavernaro I, Eckert JG, Lutowski M, Geißler D, Hertwig A, Hidde G, Bigall NC, Resch-Genger U. Influence of nanoparticle encapsulation and encoding on the surface chemistry of polymer carrier beads. Sci Rep 2023; 13:11957. [PMID: 37488159 PMCID: PMC10366211 DOI: 10.1038/s41598-023-38518-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 07/10/2023] [Indexed: 07/26/2023] Open
Abstract
Surface-functionalized polymer beads encoded with molecular luminophores and nanocrystalline emitters such as semiconductor nanocrystals, often referred to as quantum dots (QDs), or magnetic nanoparticles are broadly used in the life sciences as reporters and carrier beads. Many of these applications require a profound knowledge of the chemical nature and total number of their surface functional groups (FGs), that control bead charge, colloidal stability, hydrophobicity, and the interaction with the environment and biological systems. For bioanalytical applications, also the number of groups accessible for the subsequent functionalization with, e.g., biomolecules or targeting ligands is relevant. In this study, we explore the influence of QD encoding on the amount of carboxylic acid (COOH) surface FGs of 2 µm polystyrene microparticles (PSMPs). This is done for frequently employed oleic acid and oleylamine stabilized, luminescent core/shell CdSe QDs and two commonly used encoding procedures. This included QD addition during bead formation by a thermally induced polymerization reaction and a post synthetic swelling procedure. The accessible number of COOH groups on the surface of QD-encoded and pristine beads was quantified by two colorimetric assays, utilizing differently sized reporters and electrostatic and covalent interactions. The results were compared to the total number of FGs obtained by a conductometric titration and Fourier transform infrared spectroscopy (FTIR). In addition, a comparison of the impact of QD and dye encoding on the bead surface chemistry was performed. Our results demonstrate the influence of QD encoding and the QD-encoding strategy on the number of surface FG that is ascribed to an interaction of the QDs with the carboxylic acid groups on the bead surface. These findings are of considerable relevance for applications of nanoparticle-encoded beads and safe-by-design concepts for nanomaterials.
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Affiliation(s)
- Lena Scholtz
- Division 1.2 Biophotonics, Federal Institute for Materials Research and Testing (BAM), Richard-Willstätter-Str. 11, 12489, Berlin, Germany
- Institute for Chemistry and Biochemistry, Free University Berlin, Takustraße 3, 14195, Berlin, Germany
| | - Isabella Tavernaro
- Division 1.2 Biophotonics, Federal Institute for Materials Research and Testing (BAM), Richard-Willstätter-Str. 11, 12489, Berlin, Germany
| | - J Gerrit Eckert
- Institute of Physical Chemistry and Electrochemistry, Leibniz University Hannover, Callinstraße 3A, 30167, Hannover, Germany
| | - Marc Lutowski
- Division 1.2 Biophotonics, Federal Institute for Materials Research and Testing (BAM), Richard-Willstätter-Str. 11, 12489, Berlin, Germany
| | - Daniel Geißler
- Division 1.2 Biophotonics, Federal Institute for Materials Research and Testing (BAM), Richard-Willstätter-Str. 11, 12489, Berlin, Germany
- PolyAn GmbH, Schkopauer Ring 6, 12681, Berlin, Germany
| | - Andreas Hertwig
- Division 6.1 Surface Analysis and Interfacial Chemistry, Federal Institute for Materials Research and Testing (BAM), Unter den Eichen 87, 12205, Berlin, Germany
| | - Gundula Hidde
- Division 6.1 Surface Analysis and Interfacial Chemistry, Federal Institute for Materials Research and Testing (BAM), Unter den Eichen 87, 12205, Berlin, Germany
| | - Nadja C Bigall
- Institute of Physical Chemistry and Electrochemistry, Leibniz University Hannover, Callinstraße 3A, 30167, Hannover, Germany
- Cluster of Excellence PhoenixD (Photonics, Optics, and Engineering - Innovation Across Disciplines), 30167, Hannover, Germany
| | - Ute Resch-Genger
- Division 1.2 Biophotonics, Federal Institute for Materials Research and Testing (BAM), Richard-Willstätter-Str. 11, 12489, Berlin, Germany.
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19
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Xia Y, Fu S, Ma Q, Liu Y, Zhang N. Application of Nano-Delivery Systems in Lymph Nodes for Tumor Immunotherapy. NANO-MICRO LETTERS 2023; 15:145. [PMID: 37269391 PMCID: PMC10239433 DOI: 10.1007/s40820-023-01125-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 05/07/2023] [Indexed: 06/05/2023]
Abstract
Immunotherapy has become a promising research "hotspot" in cancer treatment. "Soldier" immune cells are not uniform throughout the body; they accumulate mostly in the immune organs such as the spleen and lymph nodes (LNs), etc. The unique structure of LNs provides the microenvironment suitable for the survival, activation, and proliferation of multiple types of immune cells. LNs play an important role in both the initiation of adaptive immunity and the generation of durable anti-tumor responses. Antigens taken up by antigen-presenting cells in peripheral tissues need to migrate with lymphatic fluid to LNs to activate the lymphocytes therein. Meanwhile, the accumulation and retaining of many immune functional compounds in LNs enhance their efficacy significantly. Therefore, LNs have become a key target for tumor immunotherapy. Unfortunately, the nonspecific distribution of the immune drugs in vivo greatly limits the activation and proliferation of immune cells, which leads to unsatisfactory anti-tumor effects. The efficient nano-delivery system to LNs is an effective strategy to maximize the efficacy of immune drugs. Nano-delivery systems have shown beneficial in improving biodistribution and enhancing accumulation in lymphoid tissues, exhibiting powerful and promising prospects for achieving effective delivery to LNs. Herein, the physiological structure and the delivery barriers of LNs were summarized and the factors affecting LNs accumulation were discussed thoroughly. Moreover, developments in nano-delivery systems were reviewed and the transformation prospects of LNs targeting nanocarriers were summarized and discussed.
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Affiliation(s)
- Yiming Xia
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China
| | - Shunli Fu
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China
| | - Qingping Ma
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China
| | - Yongjun Liu
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
| | - Na Zhang
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
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20
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Darwish GH, Massey M, Daudet G, Alde LG, Algar WR. Tetrameric Antibody Complexes and Affinity Tag Peptides for the Selective Immobilization and Imaging of Single Quantum Dots. Bioconjug Chem 2023. [PMID: 37243625 DOI: 10.1021/acs.bioconjchem.3c00142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
Colloidal semiconductor quantum dots (QDs) are of widespread interest as fluorescent labels for bioanalysis and imaging applications. Single-particle measurements have proven to be a very powerful tool for better understanding the fundamental properties and behaviors of QDs and their bioconjugates; however, a recurring challenge is the immobilization of QDs in a solution-like environment that minimizes interactions with a bulk surface. Immobilization strategies for QD-peptide conjugates are particularly underdeveloped within this context. Here, we present a novel strategy for the selective immobilization of single QD-peptide conjugates using a combination of tetrameric antibody complexes (TACs) and affinity tag peptides. A glass substrate is modified with an adsorbed layer of concanavalin A (ConA) that binds a subsequent layer of dextran that minimizes nonspecific binding. A TAC with anti-dextran and anti-affinity tag antibodies binds to the dextran-coated glass surface and to the affinity tag sequence of QD-peptide conjugates. The result is spontaneous and sequence-selective immobilization of single QDs without any chemical activation or cross-linking. Controlled immobilization of multiple colors of QDs is possible using multiple affinity tag sequences. Experiments confirmed that this approach positions the QD away from the bulk surface. The method supports real-time imaging of binding and dissociation, measurements of Förster resonance energy transfer (FRET), tracking of dye photobleaching, and detection of proteolytic activity. We anticipate that this immobilization strategy will be useful for studies of QD-associated photophysics, biomolecular interactions and processes, and digital assays.
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Affiliation(s)
- Ghinwa H Darwish
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, Canada V6T 1Z1
| | - Melissa Massey
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, Canada V6T 1Z1
| | - Gabrielle Daudet
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, Canada V6T 1Z1
| | - Luis G Alde
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, Canada V6T 1Z1
| | - W Russ Algar
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, Canada V6T 1Z1
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21
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Johnson V, Vasu S, Kumar US, Kumar M. Surface-Engineered Extracellular Vesicles in Cancer Immunotherapy. Cancers (Basel) 2023; 15:2838. [PMID: 37345176 PMCID: PMC10216164 DOI: 10.3390/cancers15102838] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 05/14/2023] [Accepted: 05/15/2023] [Indexed: 06/23/2023] Open
Abstract
Extracellular vesicles (EVs) are lipid bilayer-enclosed bodies secreted by all cell types. EVs carry bioactive materials, such as proteins, lipids, metabolites, and nucleic acids, to communicate and elicit functional alterations and phenotypic changes in the counterpart stromal cells. In cancer, cells secrete EVs to shape a tumor-promoting niche. Tumor-secreted EVs mediate communications with immune cells that determine the fate of anti-tumor therapeutic effectiveness. Surface engineering of EVs has emerged as a promising tool for the modulation of tumor microenvironments for cancer immunotherapy. Modification of EVs' surface with various molecules, such as antibodies, peptides, and proteins, can enhance their targeting specificity, immunogenicity, biodistribution, and pharmacokinetics. The diverse approaches sought for engineering EV surfaces can be categorized as physical, chemical, and genetic engineering strategies. The choice of method depends on the specific application and desired outcome. Each has its advantages and disadvantages. This review lends a bird's-eye view of the recent progress in these approaches with respect to their rational implications in the immunomodulation of tumor microenvironments (TME) from pro-tumorigenic to anti-tumorigenic ones. The strategies for modulating TME using targeted EVs, their advantages, current limitations, and future directions are discussed.
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Affiliation(s)
- Vinith Johnson
- Department of Chemical Engineering, Indian Institute of Technology, Tirupati 517619, India
| | - Sunil Vasu
- Department of Radiology, Stanford University, Stanford, CA 94305, USA
| | - Uday S. Kumar
- Department of Chemical Engineering, Indian Institute of Technology, Tirupati 517619, India
| | - Manoj Kumar
- Department of Radiology, Stanford University, Stanford, CA 94305, USA
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22
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Na Y, Zhang N, Zhong X, Gu J, Yan C, Yin S, Lei X, Zhao J, Geng F. Polylactic-co-glycolic acid-based nanoparticles modified with peptides and other linkers cross the blood-brain barrier for targeted drug delivery. Nanomedicine (Lond) 2023; 18:125-143. [PMID: 36916394 DOI: 10.2217/nnm-2022-0287] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023] Open
Abstract
Because of the blood-brain barrier, only a limited fraction of drugs can penetrate the brain. As a result, there is a need to take larger doses of the drug, which may result in numerous undesirable side effects. Over the past few decades, a plethora of research has been conducted to address this issue. In recent years, the field of nanomedicine research has reported promising findings. Currently, numerous types of polylactic-co-glycolic acid-based drug-delivery systems are being studied, and great progress has been made in the modification of their surfaces with a variety of ligands. In this review, the authors highlight the preparation of polylactic-co-glycolic acid-based nanoparticles and single- and dual-targeted peptide modifications for site-specific drug delivery into the brain.
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Affiliation(s)
- Yue Na
- Key Laboratory of Photochemistry Biomaterials & Energy Storage Materials of Heilongjiang Province, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin, Heilongjiang, 150025, China
| | - Ning Zhang
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150040, China.,Wuxi Traditional Chinese Medicine Hospital, Wuxi, Jiangsu, 214071, China
| | - Xinyu Zhong
- Key Laboratory of Photochemistry Biomaterials & Energy Storage Materials of Heilongjiang Province, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin, Heilongjiang, 150025, China
| | - Jinlian Gu
- Key Laboratory of Photochemistry Biomaterials & Energy Storage Materials of Heilongjiang Province, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin, Heilongjiang, 150025, China
| | - Chang Yan
- Key Laboratory of Photochemistry Biomaterials & Energy Storage Materials of Heilongjiang Province, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin, Heilongjiang, 150025, China
| | - Shun Yin
- Key Laboratory of Photochemistry Biomaterials & Energy Storage Materials of Heilongjiang Province, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin, Heilongjiang, 150025, China
| | - Xia Lei
- Wuxi Traditional Chinese Medicine Hospital, Wuxi, Jiangsu, 214071, China
| | - Jihui Zhao
- College of Pharmacy, Hunan University of Medicine, Huaihua, Hunan, 418000, China
| | - Fang Geng
- Key Laboratory of Photochemistry Biomaterials & Energy Storage Materials of Heilongjiang Province, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin, Heilongjiang, 150025, China
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23
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Perrins RD, McCarthy LA, Robinson A, Spry KL, Cognet V, Ferreira A, Porter J, Garcίa CE, Rodriguez MÁ, Lopez D, Perera I, Conlon K, Barrientos A, Coulter T, Pace A, Hale SJM, Ferrari E, Bachrati CZ. Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:nano12224013. [PMID: 36432299 PMCID: PMC9696180 DOI: 10.3390/nano12224013] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/07/2022] [Accepted: 11/14/2022] [Indexed: 05/06/2023]
Abstract
Cyclic arginyl-glycyl-aspartic acid peptide (cRGD) peptides show a high affinity towards αVβ3 integrin, a receptor overexpressed in many cancers. We aimed to combine the versatility of ultrasmall gold nanoparticles (usGNP) with the target selectivity of cRGD peptide for the directed delivery of a cytotoxic payload in a novel design. usGNPs were synthesized with a modified Brust-Schiffrin method and functionalized via amide coupling and ligand exchange and their uptake, intracellular trafficking, and toxicity were characterized. Our cRGD functionalized usGNPs demonstrated increased cellular uptake by αVβ3 integrin expressing cells, are internalized via clathrin-dependent endocytosis, accumulated in the lysosomes, and when loaded with mertansine led to increased cytotoxicity. Targeting via cRGD functionalization provides a mechanism to improve the efficacy, tolerability, and retention of therapeutic GNPs.
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Affiliation(s)
| | - Lee-Anne McCarthy
- School of Life Sciences, University of Lincoln, Joseph Banks Laboratories, Green Lane, Lincoln LN6 7DL, UK
| | - Angela Robinson
- Midatech Pharma Plc, 1 Caspian Point, Caspian Way, Cardiff CF10 4DQ, UK
| | - Kelly L. Spry
- Midatech Pharma Plc, 1 Caspian Point, Caspian Way, Cardiff CF10 4DQ, UK
| | - Valentin Cognet
- Midatech Pharma Plc, 1 Caspian Point, Caspian Way, Cardiff CF10 4DQ, UK
| | - Avelino Ferreira
- Midatech Pharma Plc, 1 Caspian Point, Caspian Way, Cardiff CF10 4DQ, UK
| | - John Porter
- Midatech Pharma Plc, 1 Caspian Point, Caspian Way, Cardiff CF10 4DQ, UK
| | | | | | - Diana Lopez
- Midatech Pharma Plc, 1 Caspian Point, Caspian Way, Cardiff CF10 4DQ, UK
| | - Ibon Perera
- Midatech Pharma Plc, 1 Caspian Point, Caspian Way, Cardiff CF10 4DQ, UK
| | - Kelly Conlon
- Midatech Pharma Plc, 1 Caspian Point, Caspian Way, Cardiff CF10 4DQ, UK
| | - Africa Barrientos
- Midatech Pharma Plc, 1 Caspian Point, Caspian Way, Cardiff CF10 4DQ, UK
| | - Tom Coulter
- Midatech Pharma Plc, 1 Caspian Point, Caspian Way, Cardiff CF10 4DQ, UK
| | - Alessandro Pace
- Midatech Pharma Plc, 1 Caspian Point, Caspian Way, Cardiff CF10 4DQ, UK
| | - Sarah J. M. Hale
- Midatech Pharma Plc, 1 Caspian Point, Caspian Way, Cardiff CF10 4DQ, UK
| | - Enrico Ferrari
- School of Life Sciences, University of Lincoln, Joseph Banks Laboratories, Green Lane, Lincoln LN6 7DL, UK
| | - Csanad Z. Bachrati
- School of Life Sciences, University of Lincoln, Joseph Banks Laboratories, Green Lane, Lincoln LN6 7DL, UK
- Correspondence: ; Tel.: +44-1522-886787
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24
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Wu ZC, Liu XY, Liu JY, Piao JS, Piao MG. Preparation of Betulinic Acid Galactosylated Chitosan Nanoparticles and Their Effect on Liver Fibrosis. Int J Nanomedicine 2022; 17:4195-4210. [PMID: 36134203 PMCID: PMC9484277 DOI: 10.2147/ijn.s373430] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 08/31/2022] [Indexed: 11/23/2022] Open
Abstract
Aim Liver fibrosis is mainly characterized by the formation of fibrous scars. Galactosylated chitosan (GC) has gained increasing attention as a liver-targeted drug carrier in recent years. The present study aimed to investigate the availability of betulinic acid-loaded GC nanoparticles (BA-GC-NPs) for liver protection. Covalently-conjugated galactose, recognized by asialoglycoprotein receptors exclusively expressed in hepatocytes, was employed to target the liver. Materials and Methods Galactose was coupled to chitosan by chemical covalent binding. BA-GC-NPs were synthesized by wrapping BA into NPs via ion-crosslinking method. The potential advantage of BA-GC-NP as a liver-targeting agent in the treatment of liver fibrosis has been demonstrated in vivo and in vitro. Results BA-GC-NPs with diameters <200 nm were manufactured in a virtually spherical core-shell arrangement, and BA was released consistently and continuously for 96 h, as assessed by an in vitro release assay. According to the safety evaluation, BA-GC-NPs demonstrated good biocompatibility at the cellular level and did not generate any inflammatory reaction in mice. Importantly, BA-GC-NPs showed an inherent liver-targeting potential in the uptake behavioral studies in cells and bioimaging tests in vivo. Efficacy tests revealed that administering BA-GC-NPs in a mouse model of liver fibrosis reduced the degree of liver injury in mice. Conclusion The findings showed that BA-GC-NPs form a safe and effective anti-hepatic fibrosis medication delivery strategy.
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Affiliation(s)
- Zi Chao Wu
- School of Pharmacy, Yanbian University, Yanji, 133002, People's Republic of China.,Research Institute, Shijiazhuang Yiling Pharmaceutical Co., Ltd, Shijiazhuang, 050035, People's Republic of China
| | - Xin Yu Liu
- School of Pharmacy, Yanbian University, Yanji, 133002, People's Republic of China
| | - Jia Yan Liu
- School of Pharmacy, Yanbian University, Yanji, 133002, People's Republic of China
| | - Jing Shu Piao
- School of Pharmacy, Yanbian University, Yanji, 133002, People's Republic of China
| | - Ming Guan Piao
- School of Pharmacy, Yanbian University, Yanji, 133002, People's Republic of China.,Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, People's Republic of China
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25
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Abstract
Super-resolution imaging techniques that overcome the diffraction limit of light have gained wide popularity for visualizing cellular structures with nanometric resolution. Following the pace of hardware developments, the availability of new fluorescent probes with superior properties is becoming ever more important. In this context, fluorescent nanoparticles (NPs) have attracted increasing attention as bright and photostable probes that address many shortcomings of traditional fluorescent probes. The use of NPs for super-resolution imaging is a recent development and this provides the focus for the current review. We give an overview of different super-resolution methods and discuss their demands on the properties of fluorescent NPs. We then review in detail the features, strengths, and weaknesses of each NP class to support these applications and provide examples from their utilization in various biological systems. Moreover, we provide an outlook on the future of the field and opportunities in material science for the development of probes for multiplexed subcellular imaging with nanometric resolution.
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Affiliation(s)
- Wei Li
- Key
Laboratory for Biobased Materials and Energy of Ministry of Education,
College of Materials and Energy, South China
Agricultural University, Guangzhou 510642, People’s Republic
of China
- Department
of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB3 0AS, United Kingdom
| | | | - Bingfu Lei
- Key
Laboratory for Biobased Materials and Energy of Ministry of Education,
College of Materials and Energy, South China
Agricultural University, Guangzhou 510642, People’s Republic
of China
| | - Yingliang Liu
- Key
Laboratory for Biobased Materials and Energy of Ministry of Education,
College of Materials and Energy, South China
Agricultural University, Guangzhou 510642, People’s Republic
of China
| | - Clemens F. Kaminski
- Department
of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB3 0AS, United Kingdom
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26
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Idiago-López J, Moreno-Antolín E, Eceiza M, Aizpurua JM, Grazú V, de la Fuente JM, Fratila RM. From Bench to Cell: A Roadmap for Assessing the Bioorthogonal "Click" Reactivity of Magnetic Nanoparticles for Cell Surface Engineering. Bioconjug Chem 2022; 33:1620-1633. [PMID: 35857350 PMCID: PMC9501912 DOI: 10.1021/acs.bioconjchem.2c00230] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
In this work, we report the use of bioorthogonal chemistry, specifically the strain-promoted click azide-alkyne cycloaddition (SPAAC) for the covalent attachment of magnetic nanoparticles (MNPs) on living cell membranes. Four types of MNPs were prepared, functionalized with two different stabilizing/passivation agents (a polyethylene glycol derivative and a glucopyranoside derivative, respectively) and two types of strained alkynes with different reactivities: a cyclooctyne (CO) derivative and a dibenzocyclooctyne (DBCO) derivative. The MNPs were extensively characterized in terms of physicochemical characteristics, colloidal stability, and click reactivity in suspension. Then, the reactivity of the MNPs toward azide-modified surfaces was evaluated as a closer approach to their final application in a living cell scenario. Finally, the DBCO-modified MNPs, showing superior reactivity in suspension and on surfaces, were selected for cell membrane immobilization via the SPAAC reaction on the membranes of cells engineered to express azide artificial reporters. Overall, our work provides useful insights into the appropriate surface engineering of nanoparticles to ensure a high performance in terms of bioorthogonal reactivity for biological applications.
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Affiliation(s)
- Javier Idiago-López
- Instituto de Nanociencia y Materiales de Aragón, INMA (CSIC-Universidad de Zaragoza), C/ Pedro Cerbuna 12, 50009 Zaragoza, Spain.,Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 50018 Zaragoza, Spain
| | - Eduardo Moreno-Antolín
- Instituto de Nanociencia y Materiales de Aragón, INMA (CSIC-Universidad de Zaragoza), C/ Pedro Cerbuna 12, 50009 Zaragoza, Spain
| | - Maite Eceiza
- Universidad del País Vasco, UPV-EHU, Jose Mari Korta R&D Center, 20018 Donostia San Sebastián, Spain
| | - Jesús M Aizpurua
- Universidad del País Vasco, UPV-EHU, Jose Mari Korta R&D Center, 20018 Donostia San Sebastián, Spain
| | - Valeria Grazú
- Instituto de Nanociencia y Materiales de Aragón, INMA (CSIC-Universidad de Zaragoza), C/ Pedro Cerbuna 12, 50009 Zaragoza, Spain.,Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 50018 Zaragoza, Spain
| | - Jesús M de la Fuente
- Instituto de Nanociencia y Materiales de Aragón, INMA (CSIC-Universidad de Zaragoza), C/ Pedro Cerbuna 12, 50009 Zaragoza, Spain.,Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 50018 Zaragoza, Spain
| | - Raluca M Fratila
- Instituto de Nanociencia y Materiales de Aragón, INMA (CSIC-Universidad de Zaragoza), C/ Pedro Cerbuna 12, 50009 Zaragoza, Spain.,Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 50018 Zaragoza, Spain.,Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Zaragoza, C/Pedro Cerbuna 12, 50009 Zaragoza, Spain
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27
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Strategies for the Biofunctionalization of Straining Flow Spinning Regenerated Bombyx mori Fibers. Molecules 2022; 27:molecules27134146. [PMID: 35807389 PMCID: PMC9267934 DOI: 10.3390/molecules27134146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 06/24/2022] [Accepted: 06/25/2022] [Indexed: 11/16/2022] Open
Abstract
High-performance regenerated silkworm (Bombyx mori) silk fibers can be produced efficiently through the straining flow spinning (SFS) technique. In addition to an enhanced biocompatibility that results from the removal of contaminants during the processing of the material, regenerated silk fibers may be functionalized conveniently by using a range of different strategies. In this work, the possibility of implementing various functionalization techniques is explored, including the production of fluorescent fibers that may be tracked when implanted, the combination of the fibers with enzymes to yield fibers with catalytic properties, and the functionalization of the fibers with cell-adhesion motifs to modulate the adherence of different cell lineages to the material. When considered globally, all these techniques are a strong indication not only of the high versatility offered by the functionalization of regenerated fibers in terms of the different chemistries that can be employed, but also on the wide range of applications that can be covered with these functionalized fibers.
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28
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Tella JO, Adekoya JA, Ajanaku KO. Mesoporous silica nanocarriers as drug delivery systems for anti-tubercular agents: a review. ROYAL SOCIETY OPEN SCIENCE 2022; 9:220013. [PMID: 35706676 PMCID: PMC9174711 DOI: 10.1098/rsos.220013] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 04/27/2022] [Indexed: 05/03/2023]
Abstract
The treatment and management of tuberculosis using conventional drug delivery systems remain challenging due to the setbacks involved. The lengthy and costly treatment regime and patients' non-compliance have led to drug-resistant tuberculosis, which is more difficult to treat. Also, anti-tubercular drugs currently used are poor water-soluble drugs with low bioavailability and poor therapeutic efficiency except at higher doses which causes drug-related toxicity. Novel drug delivery carrier systems such as mesoporous silica nanoparticles (MSNs) have been identified as nanomedicines capable of addressing the challenges mentioned due to their biocompatibility. The review discusses the sol-gel synthesis and chemistry of MSNs as porous drug nanocarriers, surface functionalization techniques and the influence of their physico-chemical properties on drug solubility, loading and release kinetics. It outlines the physico-chemical characteristics of MSNs encapsulated with anti-tubercular drugs.
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Affiliation(s)
| | - Joseph Adeyemi Adekoya
- Department of Chemistry, College of Science and Technology, Covenant University, Ota 112212, Nigeria
| | - Kolawole Oluseyi Ajanaku
- Department of Chemistry, College of Science and Technology, Covenant University, Ota 112212, Nigeria
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29
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Chu S, Shi X, Tian Y, Gao F. pH-Responsive Polymer Nanomaterials for Tumor Therapy. Front Oncol 2022; 12:855019. [PMID: 35392227 PMCID: PMC8980858 DOI: 10.3389/fonc.2022.855019] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 02/24/2022] [Indexed: 12/24/2022] Open
Abstract
The complexity of the tumor microenvironment presents significant challenges to cancer therapy, while providing opportunities for targeted drug delivery. Using characteristic signals of the tumor microenvironment, various stimuli-responsive drug delivery systems can be constructed for targeted drug delivery to tumor sites. Among these, the pH is frequently utilized, owing to the pH of the tumor microenvironment being lower than that of blood and healthy tissues. pH-responsive polymer carriers can improve the efficiency of drug delivery in vivo, allow targeted drug delivery, and reduce adverse drug reactions, enabling multifunctional and personalized treatment. pH-responsive polymers have gained increasing interest due to their advantageous properties and potential for applicability in tumor therapy. In this review, recent advances in, and common applications of, pH-responsive polymer nanomaterials for drug delivery in cancer therapy are summarized, with a focus on the different types of pH-responsive polymers. Moreover, the challenges and future applications in this field are prospected.
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Affiliation(s)
- Shunli Chu
- Department of Implantology, Hospital of Stomatology, Jilin University, Changchun, China
| | - Xiaolu Shi
- Department of Implantology, Hospital of Stomatology, Jilin University, Changchun, China
| | - Ye Tian
- Department of Implantology, Hospital of Stomatology, Jilin University, Changchun, China
| | - Fengxiang Gao
- Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China
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30
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Choi H, Choi K, Kim DH, Oh BK, Yim H, Jo S, Choi C. Strategies for Targeted Delivery of Exosomes to the Brain: Advantages and Challenges. Pharmaceutics 2022; 14:672. [PMID: 35336049 PMCID: PMC8948948 DOI: 10.3390/pharmaceutics14030672] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Revised: 03/10/2022] [Accepted: 03/16/2022] [Indexed: 02/08/2023] Open
Abstract
Delivering therapeutics to the central nervous system (CNS) is difficult because of the blood-brain barrier (BBB). Therapeutic delivery across the tight junctions of the BBB can be achieved through various endogenous transportation mechanisms. Receptor-mediated transcytosis (RMT) is one of the most widely investigated and used methods. Drugs can hijack RMT by expressing specific ligands that bind to receptors mediating transcytosis, such as the transferrin receptor (TfR), low-density lipoprotein receptor (LDLR), and insulin receptor (INSR). Cell-penetrating peptides and viral components originating from neurotropic viruses can also be utilized for the efficient BBB crossing of therapeutics. Exosomes, or small extracellular vesicles, have gained attention as natural nanoparticles for treating CNS diseases, owing to their potential for natural BBB crossing and broad surface engineering capability. RMT-mediated transport of exosomes expressing ligands such as LDLR-targeting apolipoprotein B has shown promising results. Although surface-modified exosomes possessing brain targetability have shown enhanced CNS delivery in preclinical studies, the successful development of clinically approved exosome therapeutics for CNS diseases requires the establishment of quantitative and qualitative methods for monitoring exosomal delivery to the brain parenchyma in vivo as well as elucidation of the mechanisms underlying the BBB crossing of surface-modified exosomes.
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Affiliation(s)
- Hojun Choi
- ILIAS Biologics Inc., Daejeon 34014, Korea; (H.C.); (K.C.); (D.-H.K.); (B.-K.O.); (H.Y.); (S.J.)
| | - Kyungsun Choi
- ILIAS Biologics Inc., Daejeon 34014, Korea; (H.C.); (K.C.); (D.-H.K.); (B.-K.O.); (H.Y.); (S.J.)
| | - Dae-Hwan Kim
- ILIAS Biologics Inc., Daejeon 34014, Korea; (H.C.); (K.C.); (D.-H.K.); (B.-K.O.); (H.Y.); (S.J.)
| | - Byung-Koo Oh
- ILIAS Biologics Inc., Daejeon 34014, Korea; (H.C.); (K.C.); (D.-H.K.); (B.-K.O.); (H.Y.); (S.J.)
| | - Hwayoung Yim
- ILIAS Biologics Inc., Daejeon 34014, Korea; (H.C.); (K.C.); (D.-H.K.); (B.-K.O.); (H.Y.); (S.J.)
| | - Soojin Jo
- ILIAS Biologics Inc., Daejeon 34014, Korea; (H.C.); (K.C.); (D.-H.K.); (B.-K.O.); (H.Y.); (S.J.)
| | - Chulhee Choi
- ILIAS Biologics Inc., Daejeon 34014, Korea; (H.C.); (K.C.); (D.-H.K.); (B.-K.O.); (H.Y.); (S.J.)
- Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea
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31
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Jiménez-Jiménez C, Moreno VM, Vallet-Regí M. Bacteria-Assisted Transport of Nanomaterials to Improve Drug Delivery in Cancer Therapy. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:288. [PMID: 35055305 PMCID: PMC8781131 DOI: 10.3390/nano12020288] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 01/08/2022] [Accepted: 01/11/2022] [Indexed: 12/12/2022]
Abstract
Currently, the design of nanomaterials for the treatment of different pathologies is presenting a major impact on biomedical research. Thanks to this, nanoparticles represent a successful strategy for the delivery of high amounts of drugs for the treatment of cancer. Different nanosystems have been designed to combat this pathology. However, the poor penetration of these nanomaterials into the tumor tissue prevents the drug from entering the inner regions of the tumor. Some bacterial strains have self-propulsion and guiding capacity thanks to their flagella. They also have a preference to accumulate in certain tumor regions due to the presence of different chemo-attractants factors. Bioconjugation reactions allow the binding of nanoparticles in living systems, such as cells or bacteria, in a simple way. Therefore, bacteria are being used as a transport vehicle for nanoparticles, facilitating their penetration and the subsequent release of the drug inside the tumor. This review would summarize the literature on the anchoring methods of diverse nanosystems in bacteria and, interestingly, their advantages and possible applications in cancer therapy.
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Affiliation(s)
- Carla Jiménez-Jiménez
- CIBER de Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, 28040 Madrid, Spain;
| | - Víctor M. Moreno
- Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria, Hospital 12 de Octubre i+12, 28040 Madrid, Spain;
| | - María Vallet-Regí
- CIBER de Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, 28040 Madrid, Spain;
- Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria, Hospital 12 de Octubre i+12, 28040 Madrid, Spain;
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32
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Choi H, Yim H, Park C, Ahn SH, Ahn Y, Lee A, Yang H, Choi C. Targeted Delivery of Exosomes Armed with Anti-Cancer Therapeutics. MEMBRANES 2022; 12:membranes12010085. [PMID: 35054611 PMCID: PMC8782002 DOI: 10.3390/membranes12010085] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 12/25/2021] [Accepted: 01/03/2022] [Indexed: 02/04/2023]
Abstract
Among extracellular vesicles, exosomes have gained great attention for their role as therapeutic vehicles for delivering various active pharmaceutical ingredients (APIs). Exosomes “armed” with anti-cancer therapeutics possess great potential for an efficient intracellular delivery of anti-cancer APIs and enhanced targetability to tumor cells. Various technologies are being developed to efficiently incorporate anti-cancer APIs such as genetic materials (miRNA, siRNA, mRNA), chemotherapeutics, and proteins into exosomes and to induce targeted delivery to tumor burden by exosomal surface modification. Exosomes can incorporate the desired therapeutic molecules via direct exogenous methods (e.g., electroporation and sonication) or indirect methods by modifying cells to produce “armed” exosomes. The targeted delivery of “armed” exosomes to tumor burden could be accomplished either by “passive” targeting using the natural tropism of exosomes or by “active” targeting via the surface engineering of exosomal membranes. Although anti-cancer exosome therapeutics demonstrated promising results in preclinical studies, success in clinical trials requires thorough validation in terms of chemistry, manufacturing, and control techniques. While exosomes possess multiple advantages over synthetic nanoparticles, challenges remain in increasing the loading efficiency of anti-cancer agents into exosomes, as well as establishing quantitative and qualitative analytical methods for monitoring the delivery of in vivo administered exosomes and exosome-incorporated anti-cancer agents to the tumor parenchyma.
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Affiliation(s)
- Hojun Choi
- ILIAS Biologics Inc., Daejeon 34014, Korea; (H.C.); (H.Y.); (C.P.); (S.-H.A.); (Y.A.); (A.L.)
| | - Hwayoung Yim
- ILIAS Biologics Inc., Daejeon 34014, Korea; (H.C.); (H.Y.); (C.P.); (S.-H.A.); (Y.A.); (A.L.)
| | - Cheolhyoung Park
- ILIAS Biologics Inc., Daejeon 34014, Korea; (H.C.); (H.Y.); (C.P.); (S.-H.A.); (Y.A.); (A.L.)
| | - So-Hee Ahn
- ILIAS Biologics Inc., Daejeon 34014, Korea; (H.C.); (H.Y.); (C.P.); (S.-H.A.); (Y.A.); (A.L.)
| | - Yura Ahn
- ILIAS Biologics Inc., Daejeon 34014, Korea; (H.C.); (H.Y.); (C.P.); (S.-H.A.); (Y.A.); (A.L.)
| | - Areum Lee
- ILIAS Biologics Inc., Daejeon 34014, Korea; (H.C.); (H.Y.); (C.P.); (S.-H.A.); (Y.A.); (A.L.)
| | - Heekyoung Yang
- In Vivo Pharmacology, 1ST Biotherapeutics Inc., Seongnam-si 13493, Korea;
| | - Chulhee Choi
- ILIAS Biologics Inc., Daejeon 34014, Korea; (H.C.); (H.Y.); (C.P.); (S.-H.A.); (Y.A.); (A.L.)
- Department of Bio and Brain Engineering, KAIST, Daejeon 34141, Korea
- Correspondence: ; Tel.: +82-42-863-4450
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33
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Erbaş A, Inci F. The Role of Ligand Rebinding and Facilitated Dissociation on the Characterization of Dissociation Rates by Surface Plasmon Resonance (SPR) and Benchmarking Performance Metrics. Methods Mol Biol 2022; 2385:237-253. [PMID: 34888723 DOI: 10.1007/978-1-0716-1767-0_11] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Surface plasmon resonance (SPR) is a real-time kinetic measurement principle that can probe the kinetic interactions between ligands and their binding sites, and lies at the backbone of pharmaceutical, biosensing, and biomolecular research. The extraction of dissociation rates from SPR-response signals often relies on several commonly adopted assumptions, one of which is the exponential decay of the dissociation part of the response signal. However, certain conditions, such as high density of binding sites or high concentration fluctuations near the surface as compared to the bulk, can lead to non-exponential decays via ligand rebinding or facilitated dissociation. Consequently, fitting the data with an exponential function can underestimate or overestimate the measured dissociation rates. Here, we describe a set of alternative fit functions that can take such effects into consideration along with plasmonic sensor design principles with key performance metrics, thereby suggesting methods for error-free high-precision extraction of the dissociation rates.
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Affiliation(s)
- Aykut Erbaş
- UNAM-National Nanotechnology Research Center and Institute of Materials Science Nanotechnology, Bilkent University, Ankara, Turkey.
| | - Fatih Inci
- UNAM-National Nanotechnology Research Center and Institute of Materials Science Nanotechnology, Bilkent University, Ankara, Turkey.
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34
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Breger JC, Ellis GA, Walper SA, Susumu K, Medintz IL. Implementing Multi-Enzyme Biocatalytic Systems Using Nanoparticle Scaffolds. Methods Mol Biol 2022; 2487:227-262. [PMID: 35687240 DOI: 10.1007/978-1-0716-2269-8_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Interest in multi-enzyme synthesis outside of cells (in vitro) is becoming far more prevalent as the field of cell-free synthetic biology grows exponentially. Such synthesis would allow for complex chemical transformations based on the exquisite specificity of enzymes in a "greener" manner as compared to organic chemical transformations. Here, we describe how nanoparticles, and in this specific case-semiconductor quantum dots, can be used to both stabilize enzymes and further allow them to self-assemble into nanocomplexes that facilitate high-efficiency channeling phenomena. Pertinent protocol information is provided on enzyme expression, choice of nanoparticulate material, confirmation of enzyme attachment to nanoparticles, assay format and tracking, data analysis, and optimization of assay formats to draw the best analytical information from the underlying processes.
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Affiliation(s)
- Joyce C Breger
- Center for Bio/Molecular Science and Engineering, Code 6900, Washington, DC, USA
| | - Gregory A Ellis
- Center for Bio/Molecular Science and Engineering, Code 6900, Washington, DC, USA
| | - Scott A Walper
- Center for Bio/Molecular Science and Engineering, Code 6900, Washington, DC, USA
| | - Kimihiro Susumu
- Optical Sciences Division, Code 5611, U.S. Naval Research Laboratory, Washington, DC, USA
- Jacobs Corporation, Hanover, MD, USA
| | - Igor L Medintz
- Center for Bio/Molecular Science and Engineering, Code 6900, Washington, DC, USA.
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35
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Biagiotti G, Angeli A, Giacomini A, Toniolo G, Landini L, Salerno G, Di Cesare Mannelli L, Ghelardini C, Mello T, Mussi S, Ravelli C, Marelli M, Cicchi S, Menna E, Ronca R, Supuran CT, Richichi B. Glyco-Coated CdSe/ZnS Quantum Dots as Nanoprobes for Carbonic Anhydrase IX Imaging in Cancer Cells. ACS APPLIED NANO MATERIALS 2021; 4:14153-14160. [PMID: 34970641 PMCID: PMC8713163 DOI: 10.1021/acsanm.1c03603] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 11/03/2021] [Indexed: 06/13/2023]
Abstract
The bioimaging of cancer cells by the specific targeting of overexpressed biomarkers is an approach that holds great promise in the identification of selective diagnostic tools. Tumor-associated human carbonic anhydrase (hCA) isoforms IX and XII have been considered so far as well-defined biomarkers, with their expression correlating with cancer progression and aggressiveness. Therefore, the availability of highly performant fluorescent tools tailored for their targeting and able to efficiently visualize such key targets is in high demand. We report here on the design and synthesis of a kind of quantum dot (QD)-based fluorescent glyconanoprobe coated with a binary mixture of ligands, which, according to the structure of the terminal domains, impart specific property sets to the fluorescent probe. Specifically, monosaccharide residues ensured the dispersibility in the biological medium, CA inhibitor residues provided specific targeting of membrane-anchored hCA IX overexpressed on bladder cancer cells, and the quantum dots imparted the optical/fluorescence properties.
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Affiliation(s)
- Giacomo Biagiotti
- Department
of Chemistry “Ugo Schiff”, University of Firenze, Via della Lastruccia 13, Sesto Fiorentino, 50019 Florence, Italy
- Consorzio
Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM, Via G. Giusti, 9, 50121 Firenze, Florence, Italy
| | - Andrea Angeli
- Department
of Neuroscience, Psychology, Drug Research and Child Health −
NEUROFARBA, Section of Pharmaceutical Chemistry, University of Firenze, Via Ugo Schiff 7, Sesto Fiorentino, 50019 Florence, Italy
| | - Arianna Giacomini
- Department
of Molecular and translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
| | - Gianluca Toniolo
- Department
of Chemistry “Ugo Schiff”, University of Firenze, Via della Lastruccia 13, Sesto Fiorentino, 50019 Florence, Italy
- Consorzio
Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM, Via G. Giusti, 9, 50121 Firenze, Florence, Italy
| | - Luca Landini
- Department
of Chemistry “Ugo Schiff”, University of Firenze, Via della Lastruccia 13, Sesto Fiorentino, 50019 Florence, Italy
| | - Gianluca Salerno
- Department
of Chemistry “Ugo Schiff”, University of Firenze, Via della Lastruccia 13, Sesto Fiorentino, 50019 Florence, Italy
| | - Lorenzo Di Cesare Mannelli
- Department
of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA
- Pharmacology and Toxicology Section, University
of Firenze, V.le Pieraccini
6, 50139 Firenze, Florence, Italy
| | - Carla Ghelardini
- Department
of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA
- Pharmacology and Toxicology Section, University
of Firenze, V.le Pieraccini
6, 50139 Firenze, Florence, Italy
| | - Tommaso Mello
- Department
of Clinical and Experimental Biomedical Sciences “Mario Serio”—Gastroenterology
Unit, University of Firenze, V.le Pieraccini 6, 50139 Firenze, Florence, Italy
| | - Silvia Mussi
- Department
of Molecular and translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
| | - Cosetta Ravelli
- Department
of Molecular and translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
| | - Marcello Marelli
- Istituto
di scienze e tecnologie chimiche “Giulio Natta”, CNR-SCITEC, Sede Fantoli, Via Fantoli 16/15, 20138 Milano Italy
| | - Stefano Cicchi
- Department
of Chemistry “Ugo Schiff”, University of Firenze, Via della Lastruccia 13, Sesto Fiorentino, 50019 Florence, Italy
- Consorzio
Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM, Via G. Giusti, 9, 50121 Firenze, Florence, Italy
| | - Enzo Menna
- Consorzio
Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM, Via G. Giusti, 9, 50121 Firenze, Florence, Italy
- Department
of Chemical Sciences, University of Padova, Via Marzolo 1, 35131 Padova, Italy
- Centre
for Mechanics of Biological Materials—CMBM, Via Marzolo 9, 35131 Padova, Italy
| | - Roberto Ronca
- Department
of Molecular and translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
| | - Claudiu T. Supuran
- Department
of Neuroscience, Psychology, Drug Research and Child Health −
NEUROFARBA, Section of Pharmaceutical Chemistry, University of Firenze, Via Ugo Schiff 7, Sesto Fiorentino, 50019 Florence, Italy
| | - Barbara Richichi
- Department
of Chemistry “Ugo Schiff”, University of Firenze, Via della Lastruccia 13, Sesto Fiorentino, 50019 Florence, Italy
- Consorzio
Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM, Via G. Giusti, 9, 50121 Firenze, Florence, Italy
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36
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Pedroso CC, Mann VR, Zuberbühler K, Bohn MF, Yu J, Altoe V, Craik CS, Cohen BE. Immunotargeting of Nanocrystals by SpyCatcher Conjugation of Engineered Antibodies. ACS NANO 2021; 15:18374-18384. [PMID: 34694776 PMCID: PMC9035480 DOI: 10.1021/acsnano.1c07856] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
Inorganic nanocrystals such as quantum dots (QDs) and upconverting nanoparticles (UCNPs) are uniquely suited for quantitative live-cell imaging and are typically functionalized with ligands to study specific receptors or cellular targets. Antibodies (Ab) are among the most useful targeting reagents owing to their high affinities and specificities, but common nanocrystal labeling methods may orient Ab incorrectly, be reversible or denaturing, or lead to Ab-NP complexes too large for some applications. Here, we show that SpyCatcher proteins, which bind and spontaneously form covalent isopeptide bonds with cognate SpyTag peptides, can conjugate engineered Ab to nanoparticle surfaces with control over stability, orientation, and stoichiometry. Compact SpyCatcher-functionalized QDs and UCNPs may be labeled with short-chain variable fragment Ab (scFv) engineered to bind urokinase-type plasminogen activator receptors (uPAR) that are overexpressed in many human cancers. Confocal imaging of anti-uPAR scFv-QD conjugates shows the antibody mediates specific binding and internalization by breast cancer cells expressing uPAR. Time-lapse imaging of photostable scFv-UCNP conjugates shows that Ab binding causes uPAR internalization with a ∼20 min half-life on the cell surface, and uPAR is internalized to endolysosomal compartments distinct from general membrane stains and without significant recycling to the cell surface. The controlled and stable conjugation of engineered Ab to NPs enables targeting of diverse receptors for live-cell study of their distribution, trafficking, and physiology.
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Affiliation(s)
- Cassio C.S. Pedroso
- The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States
| | - Victor R. Mann
- The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States
| | - Kathrin Zuberbühler
- Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, 94143, United States
| | - Markus-Frederik Bohn
- Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, 94143, United States
| | - Jessica Yu
- The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States
| | - Virginia Altoe
- The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States
| | - Charles S. Craik
- Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, 94143, United States
| | - Bruce E. Cohen
- The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States
- Division of Molecular Biophysics & Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States
- Corresponding Author:
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37
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Penders J, Nagelkerke A, Cunnane EM, Pedersen SV, Pence IJ, Coombes RC, Stevens MM. Single Particle Automated Raman Trapping Analysis of Breast Cancer Cell-Derived Extracellular Vesicles as Cancer Biomarkers. ACS NANO 2021; 15:18192-18205. [PMID: 34735133 PMCID: PMC9286313 DOI: 10.1021/acsnano.1c07075] [Citation(s) in RCA: 78] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
Extracellular vesicles (EVs) secreted by cancer cells provide an important insight into cancer biology and could be leveraged to enhance diagnostics and disease monitoring. This paper details a high-throughput label-free extracellular vesicle analysis approach to study fundamental EV biology, toward diagnosis and monitoring of cancer in a minimally invasive manner and with the elimination of interpreter bias. We present the next generation of our single particle automated Raman trapping analysis─SPARTA─system through the development of a dedicated standalone device optimized for single particle analysis of EVs. Our visualization approach, dubbed dimensional reduction analysis (DRA), presents a convenient and comprehensive method of comparing multiple EV spectra. We demonstrate that the dedicated SPARTA system can differentiate between cancer and noncancer EVs with a high degree of sensitivity and specificity (>95% for both). We further show that the predictive ability of our approach is consistent across multiple EV isolations from the same cell types. Detailed modeling reveals accurate classification between EVs derived from various closely related breast cancer subtypes, further supporting the utility of our SPARTA-based approach for detailed EV profiling.
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Affiliation(s)
- Jelle Penders
- Department
of Materials, Imperial College London, London SW7 2AZ, United Kingdom
- Department
of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom
- Institute
of Biomedical Engineering, Imperial College
London, London SW7 2AZ, United Kingdom
| | - Anika Nagelkerke
- Department
of Materials, Imperial College London, London SW7 2AZ, United Kingdom
- Department
of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom
- Institute
of Biomedical Engineering, Imperial College
London, London SW7 2AZ, United Kingdom
| | - Eoghan M. Cunnane
- Department
of Materials, Imperial College London, London SW7 2AZ, United Kingdom
- Department
of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom
- Institute
of Biomedical Engineering, Imperial College
London, London SW7 2AZ, United Kingdom
| | - Simon V. Pedersen
- Department
of Materials, Imperial College London, London SW7 2AZ, United Kingdom
- Department
of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom
- Institute
of Biomedical Engineering, Imperial College
London, London SW7 2AZ, United Kingdom
| | - Isaac J. Pence
- Department
of Materials, Imperial College London, London SW7 2AZ, United Kingdom
- Department
of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom
- Institute
of Biomedical Engineering, Imperial College
London, London SW7 2AZ, United Kingdom
| | - R. Charles Coombes
- Department
of Surgery and Cancer, Hammersmith Hospital, Imperial College, London W120HS, United Kingdom
| | - Molly M. Stevens
- Department
of Materials, Imperial College London, London SW7 2AZ, United Kingdom
- Department
of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom
- Institute
of Biomedical Engineering, Imperial College
London, London SW7 2AZ, United Kingdom
- E-mail:
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38
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Taiariol L, Chaix C, Farre C, Moreau E. Click and Bioorthogonal Chemistry: The Future of Active Targeting of Nanoparticles for Nanomedicines? Chem Rev 2021; 122:340-384. [PMID: 34705429 DOI: 10.1021/acs.chemrev.1c00484] [Citation(s) in RCA: 116] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Over the years, click and bioorthogonal reactions have been the subject of considerable research efforts. These high-performance chemical reactions have been developed to meet requirements not often provided by the chemical reactions commonly used today in the biological environment, such as selectivity, rapid reaction rate, and biocompatibility. Click and bioorthogonal reactions have been attracting increasing attention in the biomedical field for the engineering of nanomedicines. In this review, we study a compilation of articles from 2014 to the present, using the terms "click chemistry and nanoparticles (NPs)" to highlight the application of this type of chemistry for applications involving NPs intended for biomedical applications. This study identifies the main strategies offered by click and bioorthogonal chemistry, with respect to passive and active targeting, for NP functionalization with specific and multiple properties for imaging and cancer therapy. In the final part, a novel and promising approach for "two step" targeting of NPs, called pretargeting (PT), is also discussed; the principle of this strategy as well as all the studies listed from 2014 to the present are presented in more detail.
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Affiliation(s)
- Ludivine Taiariol
- Université Clermont Auvergne, Imagerie Moléculaire et Stratégies Théranostiques, BP 184, F-63005 Clermont-Ferrand, France.,Inserm U 1240, F-63000 Clermont-Ferrand, France.,Centre Jean Perrin, F-63011 Clermont-Ferrand, France
| | - Carole Chaix
- Interfaces and Biosensors, UMR 5280, CNRS, F-69100 Villeurbanne, France.,Université de Lyon, CNRS, Université Claude Bernard Lyon 1, Institut des Sciences Analytiques, UMR 5280, 5 rue de la Doua, F-69100 Villeurbanne, France
| | - Carole Farre
- Interfaces and Biosensors, UMR 5280, CNRS, F-69100 Villeurbanne, France.,Université de Lyon, CNRS, Université Claude Bernard Lyon 1, Institut des Sciences Analytiques, UMR 5280, 5 rue de la Doua, F-69100 Villeurbanne, France
| | - Emmanuel Moreau
- Université Clermont Auvergne, Imagerie Moléculaire et Stratégies Théranostiques, BP 184, F-63005 Clermont-Ferrand, France.,Inserm U 1240, F-63000 Clermont-Ferrand, France.,Centre Jean Perrin, F-63011 Clermont-Ferrand, France
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39
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Quiñones RE, Wu ZC, Boger DL. Reaction Scope of Methyl 1,2,3-Triazine-5-carboxylate with Amidines and the Impact of C4/C6 Substitution. J Org Chem 2021; 86:13465-13474. [PMID: 34499494 DOI: 10.1021/acs.joc.1c01553] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
A comprehensive study of the reaction scope of methyl 1,2,3-triazine-5-carboxylate (3a) with alkyl and aryl amidines is disclosed, reacting at room temperature at remarkable rates (<5 min, 0.1 M in CH3CN) nearly 10000-fold faster than that of unsubstituted 1,2,3-triazine and providing the product pyrimidines in high yields. C4 Methyl substitution of the 1,2,3-triazine (3b) had little effect on the rate of the reaction, whereas C4/C6 dimethyl substitution (3c) slowed the room-temperature reaction (<24 h, 0.25 M) but displayed an unaltered scope, providing the product pyrimidines in similarly high yields. Measured second-order rate constants of the reaction of 3a-c, the corresponding nitriles 3e and 3f, and 1,2,3-triazine itself (3d) with benzamidine and substituted derivatives quantitated the remarkable reactivity of 3a and 3e, verified the inverse electron demand nature of the reaction (Hammett ρ = -1.50 for substituted amidines, ρ = +7.9 for 5-substituted 1,2,3-triazine), and provided a quantitative measure of the impact of 4-methyl and 4,6-dimethyl substitution on the reactivity of the methyl 1,2,3-triazine-5-carboxylate and 5-cyano-1,2,3-triazine core heterocycles.
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40
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Canal-Martín A, Navo CD, Sáez E, Molero D, Jiménez-Osés G, Pérez-Fernández R. Nucleophilic catalysis of p-substituted aniline derivatives in acylhydrazone formation and exchange. Org Biomol Chem 2021; 19:7202-7210. [PMID: 34612342 DOI: 10.1039/d1ob00871d] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Hydrazone bond formation is a versatile reaction employed in several research fields. It is one of the most popular reversible reactions in dynamic combinatorial chemistry. Under physiological conditions, hydrazone exchange benefits from the addition of a nucleophilic catalyst. We report a mechanistic study and superior performance of electron-rich p-substituted aniline derivatives as catalysts for efficient hydrazone formation and exchange in both protic and aprotic solvents. Rigorous kinetic analyses demonstrate that imine formation with 3-hydroxy-4-nitrobenzaldehyde and aniline derivatives proceeds with unprecedented third-order kinetics in which the aldehyde consistently shows a partial order of two. Computational investigations provide insights into the mechanisms of these transformations.
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Affiliation(s)
- Andrea Canal-Martín
- Structural and Chemical Biology Department, Centro de Investigaciones Biológicas Margarita Salas, CIB-CSIC, Madrid 28040, Spain.
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41
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Geißler D, Nirmalananthan-Budau N, Scholtz L, Tavernaro I, Resch-Genger U. Analyzing the surface of functional nanomaterials-how to quantify the total and derivatizable number of functional groups and ligands. Mikrochim Acta 2021; 188:321. [PMID: 34482449 PMCID: PMC8418596 DOI: 10.1007/s00604-021-04960-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 08/08/2021] [Indexed: 12/04/2022]
Abstract
Functional nanomaterials (NM) of different size, shape, chemical composition, and surface chemistry are of increasing relevance for many key technologies of the twenty-first century. This includes polymer and silica or silica-coated nanoparticles (NP) with covalently bound surface groups, semiconductor quantum dots (QD), metal and metal oxide NP, and lanthanide-based NP with coordinatively or electrostatically bound ligands, as well as surface-coated nanostructures like micellar encapsulated NP. The surface chemistry can significantly affect the physicochemical properties of NM, their charge, their processability and performance, as well as their impact on human health and the environment. Thus, analytical methods for the characterization of NM surface chemistry regarding chemical identification, quantification, and accessibility of functional groups (FG) and surface ligands bearing such FG are of increasing importance for quality control of NM synthesis up to nanosafety. Here, we provide an overview of analytical methods for FG analysis and quantification with special emphasis on bioanalytically relevant FG broadly utilized for the covalent attachment of biomolecules like proteins, peptides, and oligonucleotides and address method- and material-related challenges and limitations. Analytical techniques reviewed include electrochemical titration methods, optical assays, nuclear magnetic resonance and vibrational spectroscopy, as well as X-ray based and thermal analysis methods, covering the last 5-10 years. Criteria for method classification and evaluation include the need for a signal-generating label, provision of either the total or derivatizable number of FG, need for expensive instrumentation, and suitability for process and production control during NM synthesis and functionalization.
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Affiliation(s)
- Daniel Geißler
- Bundesanstalt für Materialforschung und -prüfung (BAM), Division Biophotonics (BAM-1.2), Richard-Willstätter-Str. 11, 12489, Berlin, Germany
| | - Nithiya Nirmalananthan-Budau
- Bundesanstalt für Materialforschung und -prüfung (BAM), Division Biophotonics (BAM-1.2), Richard-Willstätter-Str. 11, 12489, Berlin, Germany
| | - Lena Scholtz
- Bundesanstalt für Materialforschung und -prüfung (BAM), Division Biophotonics (BAM-1.2), Richard-Willstätter-Str. 11, 12489, Berlin, Germany
| | - Isabella Tavernaro
- Bundesanstalt für Materialforschung und -prüfung (BAM), Division Biophotonics (BAM-1.2), Richard-Willstätter-Str. 11, 12489, Berlin, Germany
| | - Ute Resch-Genger
- Bundesanstalt für Materialforschung und -prüfung (BAM), Division Biophotonics (BAM-1.2), Richard-Willstätter-Str. 11, 12489, Berlin, Germany.
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42
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Abstract
Quantum dots (QDs) offer bright and robust photoluminescence among several other advantages in comparison to fluorescent dyes. In order to leverage the advantageous properties of QDs for applications in bioanalysis and imaging, simple and reliable methods for bioconjugation are required. One such method for conjugating peptides to QDs is the use of polyhistidine tags, which spontaneously bind to the surface of QDs. We describe protocols for assembling polyhistidine-tagged peptides to QDs and for characterizing the resultant QD-peptide conjugates. The latter include both electrophoretic and FRET-based protocols for confirming successful peptide assembly, estimating the maximum peptide loading capacity, and measuring the assembly kinetics. Sensors for protease activity and intracellular delivery are briefly noted as prospective applications of QD-peptide conjugates.
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43
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Qiu C, Cheng Z, Lv C, Wang R, Yu F. Development of bioorthogonal SERS imaging probe in biological and biomedical applications. CHINESE CHEM LETT 2021. [DOI: 10.1016/j.cclet.2021.03.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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44
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Moulahoum H, Ghorbanizamani F, Zihnioglu F, Timur S. Surface Biomodification of Liposomes and Polymersomes for Efficient Targeted Drug Delivery. Bioconjug Chem 2021; 32:1491-1502. [PMID: 34283580 DOI: 10.1021/acs.bioconjchem.1c00285] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Chemotherapy has seen great progress in the development of performant treatment strategies. Nanovesicles such as liposomes and polymersomes demonstrated great potential in cancer therapy. However, these nanocarriers deliver their content passively, which faces a lot of constraints during blood circulation. The main challenge resides in degradation and random delivery to normal tissues. Hence, targeting drug delivery using specific molecules (such as antibodies) grafted over the surface of these nanocarriers came as the answer to overcome many problems faced before. The advantage of using antibodies is their antigen/antibody recognition, which provides a high level of specificity to reach treatment targets. This review discusses the many techniques of nanocarrier functionalization with antibodies. The aim is to recognize the various approaches by describing their advantages and deficiencies to create the most suitable drug delivery platform. Some methods are more suitable for other applications rather than drug delivery, which can explain the low success of some proposed targeted nanocarriers. In here, a critical analysis of how every method could impact the recognition and targeting capacity of some nanocarriers (liposomes and polymersomes) is discussed to make future research more impactful and advance the field of biomedicine further.
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Affiliation(s)
- Hichem Moulahoum
- Biochemistry Department, Faculty of Science, Ege University, 35100, Bornova, Izmir, Turkey
| | - Faezeh Ghorbanizamani
- Biochemistry Department, Faculty of Science, Ege University, 35100, Bornova, Izmir, Turkey
| | - Figen Zihnioglu
- Biochemistry Department, Faculty of Science, Ege University, 35100, Bornova, Izmir, Turkey
| | - Suna Timur
- Biochemistry Department, Faculty of Science, Ege University, 35100, Bornova, Izmir, Turkey.,Central Research Testing and Analysis Laboratory Research and Application Center, Ege University, 35100, Bornova, Izmir, Turkey
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45
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Algar WR, Massey M, Rees K, Higgins R, Krause KD, Darwish GH, Peveler WJ, Xiao Z, Tsai HY, Gupta R, Lix K, Tran MV, Kim H. Photoluminescent Nanoparticles for Chemical and Biological Analysis and Imaging. Chem Rev 2021; 121:9243-9358. [PMID: 34282906 DOI: 10.1021/acs.chemrev.0c01176] [Citation(s) in RCA: 151] [Impact Index Per Article: 37.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Research related to the development and application of luminescent nanoparticles (LNPs) for chemical and biological analysis and imaging is flourishing. Novel materials and new applications continue to be reported after two decades of research. This review provides a comprehensive and heuristic overview of this field. It is targeted to both newcomers and experts who are interested in a critical assessment of LNP materials, their properties, strengths and weaknesses, and prospective applications. Numerous LNP materials are cataloged by fundamental descriptions of their chemical identities and physical morphology, quantitative photoluminescence (PL) properties, PL mechanisms, and surface chemistry. These materials include various semiconductor quantum dots, carbon nanotubes, graphene derivatives, carbon dots, nanodiamonds, luminescent metal nanoclusters, lanthanide-doped upconversion nanoparticles and downshifting nanoparticles, triplet-triplet annihilation nanoparticles, persistent-luminescence nanoparticles, conjugated polymer nanoparticles and semiconducting polymer dots, multi-nanoparticle assemblies, and doped and labeled nanoparticles, including but not limited to those based on polymers and silica. As an exercise in the critical assessment of LNP properties, these materials are ranked by several application-related functional criteria. Additional sections highlight recent examples of advances in chemical and biological analysis, point-of-care diagnostics, and cellular, tissue, and in vivo imaging and theranostics. These examples are drawn from the recent literature and organized by both LNP material and the particular properties that are leveraged to an advantage. Finally, a perspective on what comes next for the field is offered.
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Affiliation(s)
- W Russ Algar
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
| | - Melissa Massey
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
| | - Kelly Rees
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
| | - Rehan Higgins
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
| | - Katherine D Krause
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
| | - Ghinwa H Darwish
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
| | - William J Peveler
- School of Chemistry, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, U.K
| | - Zhujun Xiao
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
| | - Hsin-Yun Tsai
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
| | - Rupsa Gupta
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
| | - Kelsi Lix
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
| | - Michael V Tran
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
| | - Hyungki Kim
- Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
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Ellis GA, Díaz SA, Medintz IL. Enhancing enzymatic performance with nanoparticle immobilization: improved analytical and control capability for synthetic biochemistry. Curr Opin Biotechnol 2021; 71:77-90. [PMID: 34293630 DOI: 10.1016/j.copbio.2021.06.021] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/26/2021] [Accepted: 06/28/2021] [Indexed: 12/25/2022]
Abstract
Enzymes are incredibly potent catalysts with the potential for rapid turnover rates and exquisite specificity, leading to their desired use in multiple biotechnological processes. Yet using these natural catalysts outside of their evolved role can necessitate significant engineering. Immobilization onto microscale (or larger) scaffolds can impart industrially-desired properties but often sacrifices enzymatic activity for long-term stability; in contrast, nanoparticle (NP) conjugation of enzymes can preserve or even enhance their activity. Here, we focus on recent examples of enzyme immobilization onto NPs as a method to improve their industrial applicability. We highlight the analytical methods that are used to both characterize such enhancement along with provide insight into the phenomena that give rise to it. Finally, a short perspective addresses how to adapt lessons learned at the bench about this phenomena to larger-scale biotechnological applications.
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Affiliation(s)
- Gregory A Ellis
- Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, D.C., 20375, USA
| | - Sebastían A Díaz
- Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, D.C., 20375, USA
| | - Igor L Medintz
- Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, D.C., 20375, USA.
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Choi H, Choi Y, Yim HY, Mirzaaghasi A, Yoo JK, Choi C. Biodistribution of Exosomes and Engineering Strategies for Targeted Delivery of Therapeutic Exosomes. Tissue Eng Regen Med 2021; 18:499-511. [PMID: 34260047 PMCID: PMC8325750 DOI: 10.1007/s13770-021-00361-0] [Citation(s) in RCA: 131] [Impact Index Per Article: 32.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 06/03/2021] [Accepted: 06/09/2021] [Indexed: 02/06/2023] Open
Abstract
Exosomes are cell-secreted nano-sized vesicles which deliver diverse biological molecules for intercellular communication. Due to their therapeutic potential, exosomes have been engineered in numerous ways for efficient delivery of active pharmaceutical ingredients to various target organs, tissues, and cells. In vivo administered exosomes are normally delivered to the liver, spleen, kidney, lung, and gastrointestinal tract and show rapid clearance from the blood circulation after systemic injection. The biodistribution and pharmacokinetics (PK) of exosomes can be modulated by engineering various factors such as cellular origin and membrane protein composition of exosomes. Recent advances accentuate the potential of targeted delivery of engineered exosomes even to the most challenging organs including the central nervous system. Major breakthroughs have been made related to various imaging techniques for monitoring in vivo biodistribution and PK of exosomes, as well as exosomal surface engineering technologies for inducing targetability. For inducing targeted delivery, therapeutic exosomes can be engineered to express various targeting moieties via direct modification methods such as chemically modifying exosomal surfaces with covalent/non-covalent bonds, or via indirect modification methods by genetically engineering exosome-producing cells. In this review, we describe the current knowledge of biodistribution and PK of exosomes, factors determining the targetability and organotropism of exosomes, and imaging technologies to monitor in vivo administered exosomes. In addition, we highlight recent advances in strategies for inducing targeted delivery of exosomes to specific organs and cells.
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Affiliation(s)
- Hojun Choi
- ILIAS Biologics Incorporated, 40-20, Techno 6-ro, Yuseong-gu, Daejeon, 34014, Republic of Korea
| | - Yoorim Choi
- ILIAS Biologics Incorporated, 40-20, Techno 6-ro, Yuseong-gu, Daejeon, 34014, Republic of Korea
| | - Hwa Young Yim
- ILIAS Biologics Incorporated, 40-20, Techno 6-ro, Yuseong-gu, Daejeon, 34014, Republic of Korea
| | - Amin Mirzaaghasi
- Department of Bio and Brain Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - Jae-Kwang Yoo
- ILIAS Biologics Incorporated, 40-20, Techno 6-ro, Yuseong-gu, Daejeon, 34014, Republic of Korea.
| | - Chulhee Choi
- ILIAS Biologics Incorporated, 40-20, Techno 6-ro, Yuseong-gu, Daejeon, 34014, Republic of Korea.
- Department of Bio and Brain Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.
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Abu-Dief A, Alsehli M, Al-Enizi A, Nafady A. Recent Advances in Mesoporous Silica Nanoparticles for Targeted Drug Delivery applications. Curr Drug Deliv 2021; 19:436-450. [PMID: 34238185 DOI: 10.2174/1567201818666210708123007] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 03/15/2021] [Accepted: 04/17/2021] [Indexed: 11/22/2022]
Abstract
Nanotechnology provides the means to design and fabricate delivery vehicles capable of overcoming physiologically imposed obstacles and undesirable side effects of systemic drug delivery. This protocol allows maximal targeting effectiveness and therefore enhances therapeutic efficiency. In recent years, mesoporous silica nanoparticles (MSNPs) have sparked interest in the nanomedicine research community, particularly for their promising applications in cancer treatment. The intrinsic physio-chemical stability, facile functionalization, high surface area, low toxicity, and great loading capacity for a wide range of chemotherapeutic agents make MSNPs very appealing candidates for controllable drug delivery systems. Importantly, the peculiar nanostructures of MSNPs enabled them to serve as an effective drug, gene, protein, and antigen delivery vehicle for a variety of therapeutic regimens. For these reasons, in this review article, we underscore the recent progress in the design and synthesis of MSNPs and the parameters influencing their characteristic features and activities. In addition, the process of absorption, dissemination, and secretion by injection or oral management of MSNPs are also discussed, as they are key directions for the potential utilization of MSNPs. Factors influencing the in vivo fate of MSNPs will also be highlighted, with the main focus on particle size, morphology, porosity, surface functionality, and oxidation. Given that combining other functional materials with MSNPs may increase their biological compatibility, monitor drug discharge, or improve absorption by tumor cells coated MSNPs; these aspects are also covered and discussed herein.
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Affiliation(s)
- Ahmed Abu-Dief
- Chemistry Department, Faculty of Science, Taibah University, Madinah, Saudi Arabia
| | - Mosa Alsehli
- Chemistry Department, Faculty of Science, Taibah University, Madinah, Saudi Arabia
| | - Abdullah Al-Enizi
- Chemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Ayman Nafady
- Chemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
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Sarrett SM, Keinänen O, Dayts EJ, Dewaele-Le Roi G, Rodriguez C, Carnazza KE, Zeglis BM. Inverse electron demand Diels-Alder click chemistry for pretargeted PET imaging and radioimmunotherapy. Nat Protoc 2021; 16:3348-3381. [PMID: 34127865 PMCID: PMC8917728 DOI: 10.1038/s41596-021-00540-2] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 03/22/2021] [Indexed: 11/08/2022]
Abstract
Radiolabeled antibodies have shown promise as tools for both the nuclear imaging and endoradiotherapy of cancer, but the protracted circulation time of radioimmunoconjugates can lead to high radiation doses to healthy tissues. To circumvent this issue, we have developed an approach to positron emission tomography (PET) imaging and radioimmunotherapy (RIT) predicated on radiolabeling the antibody after it has reached its target within the body. This in vivo pretargeting strategy is based on the rapid and bio-orthogonal inverse electron demand Diels-Alder reaction between tetrazine (Tz) and trans-cyclooctene (TCO). Pretargeted PET imaging and RIT using TCO-modified antibodies in conjunction with Tz-bearing radioligands produce high activity concentrations in target tissues as well as reduced radiation doses to healthy organs compared to directly labeled radioimmunoconjugates. Herein, we describe how to prepare a TCO-modified antibody (humanized A33-TCO) as well as how to synthesize two Tz-bearing radioligands: one labeled with the positron-emitting radiometal copper-64 ([64Cu]Cu-SarAr-Tz) and one labeled with the β-emitting radiolanthanide lutetium-177 ([177Lu]Lu-DOTA-PEG7-Tz). We also provide a detailed description of pretargeted PET and pretargeted RIT experiments in a murine model of human colorectal carcinoma. Proper training in both radiation safety and the handling of laboratory mice is required for the successful execution of this protocol.
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Affiliation(s)
- Samantha M Sarrett
- Department of Chemistry, Hunter College, City University of New York, New York, NY, USA
- PhD Program in Biochemistry, Graduate Center of the City University of New York, New York, NY, USA
| | - Outi Keinänen
- Department of Chemistry, Hunter College, City University of New York, New York, NY, USA
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Chemistry, Radiochemistry, University of Helsinki, Helsinki, Finland
| | - Eric J Dayts
- Department of Chemistry, Hunter College, City University of New York, New York, NY, USA
| | - Guillaume Dewaele-Le Roi
- Department of Chemistry, Hunter College, City University of New York, New York, NY, USA
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Ph.D. Program in Chemistry, Graduate Center of the City University of New York, New York, NY, USA
| | - Cindy Rodriguez
- Department of Chemistry, Hunter College, City University of New York, New York, NY, USA
- Ph.D. Program in Chemistry, Graduate Center of the City University of New York, New York, NY, USA
| | - Kathryn E Carnazza
- Brain and Mind Research Institute & Appel Institute for Alzheimer's Disease Research, Weill Cornell Medical College, New York, NY, USA
| | - Brian M Zeglis
- Department of Chemistry, Hunter College, City University of New York, New York, NY, USA.
- PhD Program in Biochemistry, Graduate Center of the City University of New York, New York, NY, USA.
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Ph.D. Program in Chemistry, Graduate Center of the City University of New York, New York, NY, USA.
- Department of Radiology, Weill Cornell Medical College, New York, NY, USA.
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Heiss TK, Dorn RS, Prescher JA. Bioorthogonal Reactions of Triarylphosphines and Related Analogues. Chem Rev 2021; 121:6802-6849. [PMID: 34101453 PMCID: PMC10064493 DOI: 10.1021/acs.chemrev.1c00014] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Bioorthogonal phosphines were introduced in the context of the Staudinger ligation over 20 years ago. Since that time, phosphine probes have been used in myriad applications to tag azide-functionalized biomolecules. The Staudinger ligation also paved the way for the development of other phosphorus-based chemistries, many of which are widely employed in biological experiments. Several reviews have highlighted early achievements in the design and application of bioorthogonal phosphines. This review summarizes more recent advances in the field. We discuss innovations in classic Staudinger-like transformations that have enabled new biological pursuits. We also highlight relative newcomers to the bioorthogonal stage, including the cyclopropenone-phosphine ligation and the phospha-Michael reaction. The review concludes with chemoselective reactions involving phosphite and phosphonite ligations. For each transformation, we describe the overall mechanism and scope. We also showcase efforts to fine-tune the reagents for specific functions. We further describe recent applications of the chemistries in biological settings. Collectively, these examples underscore the versatility and breadth of bioorthogonal phosphine reagents.
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