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Otgaar TC, Bernert M, Morris G, Baichan P, Bignoux MJ, Letsolo B, Weiss SFT, Ferreira E. 37 kDa LRP::FLAG enhances telomerase activity and reduces ageing markers in vivo. Cell Mol Life Sci 2025; 82:83. [PMID: 39985566 PMCID: PMC11846807 DOI: 10.1007/s00018-025-05593-0] [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: 07/16/2024] [Revised: 12/30/2024] [Accepted: 01/13/2025] [Indexed: 02/24/2025]
Abstract
Ageing is a degenerative process characterised by a decline in physiological functioning of the organism. One of the core regulators of cellular ageing are telomeres, repetitive DNA sequences of TTAGGG that cap the ends of chromosomes and are maintained by the ribonucleoprotein complex, telomerase. Age-dependent progressive loss of the telomere ends eventually induces cell cycle arrest for the induction of either replicative senescence or apoptosis. It was previously established that overexpression of the 37 kDa/ 67 kDa laminin receptor (LRP/LR) increased telomerase activity and telomere length while concomitantly reducing senescence markers in aged normal cells in vitro. Therefore, it was hypothesized that elevating LRP/LR in vivo may increase telomerase activity and hinder the ageing process on an organism scale. To this end, aged C57BL/6J mice were treated/transfected to induce an overexpression of LRP::FLAG. Various physiological tests and histological analyses were performed to assess overall organism fitness as well as to discern the treatments' ability at reducing tissue degeneration and atrophy. It was found that mice overexpressing LRP::FLAG displayed improved physiological characteristics and markedly less tissue degeneration and atrophy when compared to control and non-treated mice. Alongside these improvements, certain organs displayed increased telomerase activity with a corresponding elongation in average telomere length. In addition the overexpression of LRP::FLAG significantly improved various proliferative and anti-ageing associated proteins while causing a concomitant decrease in senescence associated proteins. These findings are therefore indicative of a novel function of LRP/LR delaying the onset of senescence, while also promoting healthier ageing through elevating TERT and telomerase activity.
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Affiliation(s)
- Tyrone C Otgaar
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, Johannesburg, 2050, Republic of South Africa
| | - Martin Bernert
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, Johannesburg, 2050, Republic of South Africa
| | - Gavin Morris
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, Johannesburg, 2050, Republic of South Africa
| | - Pavan Baichan
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, Johannesburg, 2050, Republic of South Africa
| | - Monique J Bignoux
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, Johannesburg, 2050, Republic of South Africa
| | - Boitelo Letsolo
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, Johannesburg, 2050, Republic of South Africa
| | - Stefan F T Weiss
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, Johannesburg, 2050, Republic of South Africa
| | - Eloise Ferreira
- School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, Johannesburg, 2050, Republic of South Africa.
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2
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Tenchov R, Hughes KJ, Ganesan M, Iyer KA, Ralhan K, Lotti Diaz LM, Bird RE, Ivanov JM, Zhou QA. Transforming Medicine: Cutting-Edge Applications of Nanoscale Materials in Drug Delivery. ACS NANO 2025; 19:4011-4038. [PMID: 39823199 PMCID: PMC11803921 DOI: 10.1021/acsnano.4c09566] [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: 07/16/2024] [Revised: 12/23/2024] [Accepted: 12/27/2024] [Indexed: 01/19/2025]
Abstract
Since their inception in the early 1960s, the development and use of nanoscale materials have progressed tremendously, and their roles in diverse fields ranging from human health to energy and electronics are undeniable. The application of nanotechnology inventions has revolutionized many aspects of everyday life including various medical applications and specifically drug delivery systems, maximizing the therapeutic efficacy of the contained drugs by means of bioavailability enhancement or minimization of adverse effects. In this review, we utilize the CAS Content Collection, a vast repository of scientific information extracted from journal and patent publications, to analyze trends in nanoscience research relevant to drug delivery in an effort to provide a comprehensive and detailed picture of the use of nanotechnology in this field. We examine the publication landscape in the area to provide insights into current knowledge advances and developments. We review the major classes of nanosized drug delivery systems, their delivery routes, and targeted diseases. We outline the most discussed concepts and assess the advantages of various nanocarriers. The objective of this review is to provide a broad overview of the evolving landscape of current knowledge regarding nanosized drug delivery systems, to outline challenges, and to evaluate growth opportunities. The merit of the review stems from the extensive, wide-ranging coverage of the most up-to-date scientific information, allowing unmatched breadth of landscape analysis and in-depth insights.
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Affiliation(s)
- Rumiana Tenchov
- CAS,
a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | - Kevin J. Hughes
- CAS,
a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | | | - Kavita A. Iyer
- CAS,
a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | | | - Leilani M. Lotti Diaz
- CAS,
a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | - Robert E. Bird
- CAS,
a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | - Julian M. Ivanov
- CAS,
a division of the American Chemical Society, Columbus, Ohio 43210, United States
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3
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Kąpa M, Koryciarz I, Kustosik N, Jurowski P, Pniakowska Z. Future Directions in Diabetic Retinopathy Treatment: Stem Cell Therapy, Nanotechnology, and PPARα Modulation. J Clin Med 2025; 14:683. [PMID: 39941353 PMCID: PMC11818668 DOI: 10.3390/jcm14030683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 01/15/2025] [Accepted: 01/17/2025] [Indexed: 02/16/2025] Open
Abstract
This narrative review focuses on innovative treatment approaches to diabetic retinopathy to meet the urgent demand for advancements in managing both the early and late stages of the disease. Recent studies highlight the potential of adipose stem cells and their secreted factors in mitigating the retinal complications of diabetes, with promising results in improving visual acuity and reducing inflammation and angiogenesis in diabetic retinopathy. However, caution is warranted regarding the safety and long-term therapeutic effects of adipose stem cells transplantation. Bone marrow mesenchymal stem cells can also mitigate retinal damage in diabetic retinopathy. Studies demonstrate that bone marrow mesenchymal stem cells-derived exosomes can suppress the Wnt/β-catenin pathway, reducing oxidative stress, inflammation, and angiogenesis in the diabetic retina, offering promise for future diabetic retinopathy treatments. Nanotechnology has the ability to precisely target the retina and minimize systemic side effects. Nanoparticles and nanocarriers offer improved bioavailability, sustained release of therapeutics, and potential for synergistic effects. They can be a new way of effective treatment and prevention of diabetic retinopathy. Activation and modulation of PPARα as a means for diabetic retinopathy treatment has been widely investigated in recent years and demonstrated promising effects in clinical trials. PPARα activation turned out to be a promising therapeutic method for treating dyslipidemia, inflammation, and insulin sensitivity. The combination of PPARα modulators with small molecules offers an interesting perspective for retinal diseases' therapy.
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Affiliation(s)
- Maria Kąpa
- Department of Ophthalmology and Vision Rehabilitation, Medical University of Lodz, 90-549 Lodz, Poland; (M.K.); (N.K.); (P.J.); (Z.P.)
| | - Iga Koryciarz
- Department of Ophthalmology and Vision Rehabilitation, Medical University of Lodz, 90-549 Lodz, Poland; (M.K.); (N.K.); (P.J.); (Z.P.)
| | - Natalia Kustosik
- Department of Ophthalmology and Vision Rehabilitation, Medical University of Lodz, 90-549 Lodz, Poland; (M.K.); (N.K.); (P.J.); (Z.P.)
| | - Piotr Jurowski
- Department of Ophthalmology and Vision Rehabilitation, Medical University of Lodz, 90-549 Lodz, Poland; (M.K.); (N.K.); (P.J.); (Z.P.)
| | - Zofia Pniakowska
- Department of Ophthalmology and Vision Rehabilitation, Medical University of Lodz, 90-549 Lodz, Poland; (M.K.); (N.K.); (P.J.); (Z.P.)
- Optegra Eye Clinic, 90-127 Lodz, Poland
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4
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Tilden SG, Ricco MH, Hemann EA, Anchordoquy TJ. Exploiting a type III interferon response to improve chemotherapeutic safety and efficacy. Eur J Pharm Sci 2025; 204:106974. [PMID: 39608735 PMCID: PMC11753202 DOI: 10.1016/j.ejps.2024.106974] [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: 08/14/2024] [Revised: 11/22/2024] [Accepted: 11/25/2024] [Indexed: 11/30/2024]
Abstract
Immune reactions to nanomedicines can be detrimental to the patient and compromise efficacy. However, our recent study characterizing the effects of a type III interferon (IFN-λ) response to lipid nanoparticles complexed with nucleic acids (lipoplexes) suggests that an IFN-λ pretreatment can increase tumor accumulation while decreasing off-target distribution of chemotherapeutic nanomedicines. This project provides a direct follow-up to our previously published works by clarifying 1) which cell type(s) can produce IFN-λ in response to lipoplexes and how the effects of IFN-λ may be propagated in humans. Additionally, we demonstrate 2) that an IFN-λ pretreatment is also capable of altering the accumulation profile of chemotherapeutic small molecules like doxorubicin. Finally, we determined 3) that the subcutaneous administration route for an IFN-λ pretreatment is the most efficacious, and 4) that an IFN-λ pretreatment can significantly increase the survival time of mice receiving Doxil® in a murine CT26 tumor model. With several chemotherapeutic nanomedicines available in the clinic and an IFN-λ product recently completing late phase clinical trials, this study provides the model for a novel anti-cancer treatment regime that can be rapidly translated to the clinic and improve the efficacy of contemporary treatment protocols.
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Affiliation(s)
- Scott G Tilden
- University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO.
| | - Madison H Ricco
- University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Emily A Hemann
- Ohio State University, Ohio State University College of Medicine, Columbus, OH
| | - Thomas J Anchordoquy
- University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO
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5
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El-Zahaby SA, Kaur L, Sharma A, Prasad AG, Wani AK, Singh R, Zakaria MY. Lipoplexes' Structure, Preparation, and Role in Managing Different Diseases. AAPS PharmSciTech 2024; 25:131. [PMID: 38849687 DOI: 10.1208/s12249-024-02850-6] [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: 02/18/2024] [Accepted: 05/23/2024] [Indexed: 06/09/2024] Open
Abstract
Lipid-based vectors are becoming promising alternatives to traditional therapies over the last 2 decades specially for managing life-threatening diseases like cancer. Cationic lipids are the most prevalent non-viral vectors utilized in gene delivery. The increasing number of clinical trials about lipoplex-based gene therapy demonstrates their potential as well-established technology that can provide robust gene transfection. In this regard, this review will summarize this important point. These vectors however have a modest transfection efficiency. This limitation can be partly addressed by using functional lipids that provide a plethora of options for investigating nucleic acid-lipid interactions as well as in vitro and in vivo nucleic acid delivery for biomedical applications. Despite their lower gene transfer efficiency, lipid-based vectors such as lipoplexes have several advantages over viral ones: they are less toxic and immunogenic, can be targeted, and are simple to produce on a large scale. Researchers are actively investigating the parameters that are essential for an effective lipoplex delivery method. These include factors that influence the structure, stability, internalization, and transfection of the lipoplex. Thorough understanding of the design principles will enable synthesis of customized lipoplex formulations for life-saving therapy.
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Affiliation(s)
- Sally A El-Zahaby
- Department of Pharmaceutics and Industrial Pharmacy, PharmD Program, Egypt-Japan University of Science and Technology (E-JUST), Alexandria, Egypt.
| | - Lovepreet Kaur
- School of Bioengineering and Biosciences, Lovely Professional University, Jalandhar, 144411, Punjab, India
| | - Ankur Sharma
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland, UK
| | - Aprameya Ganesh Prasad
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA
| | - Atif Khurshid Wani
- School of Bioengineering and Biosciences, Lovely Professional University, Jalandhar, 144411, Punjab, India
| | - Rattandeep Singh
- School of Bioengineering and Biosciences, Lovely Professional University, Jalandhar, 144411, Punjab, India
| | - Mohamed Y Zakaria
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Port Said University, Port Said, 42526, Egypt
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Salman International University, Ras Sudr, 46612, South Sinai, Egypt
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6
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Schroder R, Dorsey PJ, Vanderburgh J, Xu W, D'Addio SM, Klein L, Gindy M, Su Y. Probing Molecular Packing of Lipid Nanoparticles from 31P Solution and Solid-State NMR. Anal Chem 2024; 96:2464-2473. [PMID: 38306310 DOI: 10.1021/acs.analchem.3c04430] [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: 02/04/2024]
Abstract
Lipid nanoparticles (LNPs) are intricate multicomponent systems widely recognized for their efficient delivery of oligonucleotide cargo to host cells. Gaining insights into the molecular properties of LNPs is crucial for their effective design and characterization. However, analysis of their internal structure at the molecular level presents a significant challenge. This study introduces 31P nuclear magnetic resonance (NMR) methods to acquire structural and dynamic information about the phospholipid envelope of LNPs. Specifically, we demonstrate that the 31P chemical shift anisotropy (CSA) parameters serve as a sensitive indicator of the molecular assembly of distearoylphosphatidylcholine (DSPC) lipids within the particles. An analytical protocol for measuring 31P CSA is developed, which can be implemented using either solution NMR or solid-state NMR, offering wide accessibility and adaptability. The capability of this method is demonstrated using both model DSPC liposomes and real-world pharmaceutical LNP formulations. Furthermore, our method can be employed to investigate the impact of formulation processes and composition on the assembly of specifically LNP particles or, more generally, phospholipid-based delivery systems. This makes it an indispensable tool for evaluating critical pharmaceutical properties such as structural homogeneity, batch-to-batch reproducibility, and the stability of the particles.
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Affiliation(s)
- Ryan Schroder
- Analytical Research & Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States
| | - Phillip J Dorsey
- Pharmaceutical Sciences and Clinical Supply, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
| | - Joe Vanderburgh
- Pharmaceutical Sciences and Clinical Supply, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
| | - Wei Xu
- Analytical Research & Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States
| | - Suzanne M D'Addio
- Pharmaceutical Sciences and Clinical Supply, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
| | - Lee Klein
- Analytical Research & Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States
| | - Marian Gindy
- Small Molecule Science and Technology, Merck & Co., Inc., Rahway, New Jersey 07065, United States
| | - Yongchao Su
- Analytical Research & Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States
- Pharmaceutical Sciences and Clinical Supply, Merck & Co., Inc., West Point, Pennsylvania 19486, United States
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7
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Garg A, Agrawal R, Chopra H, Singh T, Chaudhary R, Tankara A. A Glance on Nanovaccine: A Potential Approach for Disease Prevention. Curr Pharm Biotechnol 2024; 25:1406-1418. [PMID: 37861010 DOI: 10.2174/0113892010254221231006100659] [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: 03/29/2023] [Revised: 08/03/2023] [Accepted: 08/18/2023] [Indexed: 10/21/2023]
Abstract
There are several vaccines available for preventing various bacterial and viral infections, but still, there are many challenges that require the development of noninvasive, more efficient, and active vaccines. The advancement in biotechnological tools has provided safer antigens, such as nucleic acids, proteins etc., but due to their lower immunogenic property, adjuvants of stronger immune response are required. Nanovaccines are effective vaccines when compared with conventional vaccines as they can induce both Humoral and cell-mediated immune responses and also provide longer immunogenic memory. The nanocarriers used in vaccines act as adjuvant. They provide site-specific delivery of antigens and can be used in conjugation with immunostimulatory molecules for enhancing adjuvant therapy. The nanovaccines avoid degrading cell pathways and provide effective absorption into blood vessels. The higher potential of nanovaccines to treat various diseases, such as acquired immuno deficiency syndrome, cancer, tuberculosis, malaria and many others, along with their immunological mechanisms and different types, have been discussed in the review.
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Affiliation(s)
- Akash Garg
- Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura-Delhi Road, P.O Chhatikara, Mathura, 281001, Uttar Pradesh, India
| | - Rutvi Agrawal
- Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura-Delhi Road, P.O Chhatikara, Mathura, 281001, Uttar Pradesh, India
| | - Himansu Chopra
- Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura-Delhi Road, P.O Chhatikara, Mathura, 281001, Uttar Pradesh, India
| | - Talever Singh
- Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura-Delhi Road, P.O Chhatikara, Mathura, 281001, Uttar Pradesh, India
| | - Ramkumar Chaudhary
- Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura-Delhi Road, P.O Chhatikara, Mathura, 281001, Uttar Pradesh, India
| | - Abhishek Tankara
- Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura-Delhi Road, P.O Chhatikara, Mathura, 281001, Uttar Pradesh, India
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8
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Tilden SG, Ricco MH, Hemann EA, Anchordoquy TJ. Reducing off-target drug accumulation by exploiting a type-III interferon response. J Control Release 2023; 358:729-738. [PMID: 37230293 PMCID: PMC10389760 DOI: 10.1016/j.jconrel.2023.05.029] [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: 02/06/2023] [Revised: 05/17/2023] [Accepted: 05/20/2023] [Indexed: 05/27/2023]
Abstract
Nanomedicines have been touted as the future of cancer therapy for decades. However, the field of tumor-targeted nanomedicine has failed to significantly advance toward becoming the primary choice for cancer intervention. One of the largest obstacles that has yet to be overcome is off-target accumulation of the nanoparticles. We propose a novel approach to tumor delivery by focusing on decreasing off-target accumulation of nanomedicines rather than directly increasing tumor delivery. Acknowledging a poorly understood "refractory" response to intravenously injected gene therapy vectors observed in ours and other studies, we hypothesize that virus-like particles (lipoplexes) can be utilized to initiate an anti-viral innate immune response that limits off-target accumulation of subsequently administered nanoparticles. Indeed, our results show a significant reduction in the deposition of both dextran and Doxil® in major organs with a concurrent increase in plasma and tumor accumulation when injection occurred 24 h after a lipoplex injection. Furthermore, our data showing that the direct injection of interferon lambda (IFN-λ) is capable of eliciting this response demonstrates a central role for this type III interferon in limiting accumulation in non-tumor tissues.
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Affiliation(s)
- Scott G Tilden
- University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America.
| | - Madison H Ricco
- University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America
| | - Emily A Hemann
- Ohio State University, Ohio State University College of Medicine, Columbus, OH, United States of America
| | - Thomas J Anchordoquy
- University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America
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9
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Hashemi Goradel N, Nemati M, Bakhshandeh A, Arashkia A, Negahdari B. Nanovaccines for cancer immunotherapy: Focusing on complex formation between adjuvant and antigen. Int Immunopharmacol 2023; 117:109887. [PMID: 36841155 DOI: 10.1016/j.intimp.2023.109887] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 01/29/2023] [Accepted: 02/10/2023] [Indexed: 02/27/2023]
Abstract
As an interesting cancer immunotherapy approach, cancer vaccines have been developed to deliver tumor antigens and adjuvants to antigen-presenting cells (APCs). Although the safety and easy production shifted the vaccine designing platforms toward the subunit vaccines, their efficacy is limited due to inefficient vaccine delivery. Nanotechnology-based vaccines, called nanovaccines, address the delivery limitations through co-delivery of antigens and adjuvants into lymphoid organs and APCs and their intracellular release, leading to cross-presentation of antigens and induction of potent anti-tumor immune responses. Although the nanovaccines, either as encapsulating agents or biomimetic nanoparticles, exert the desired anti-tumor activities, there is evidence that the mixing formulation to form nanocomplexes between antigens and adjuvants based on the electrostatic interactions provokes high levels of immune responses owing to Ags' availability and faster release. Here, we summarized the various platforms for developing cancer vaccines and the advantages of using delivery systems. The cancer nanovaccines, including nanoparticle-based and biomimetic-based nanovaccines, are discussed in detail. Finally, we focused on the nanocomplexes formation between antigens and adjuvants as promising cancer nanovaccine platforms.
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Affiliation(s)
- Nasser Hashemi Goradel
- Department of Medical Biotechnology, Maragheh University of Medical Sciences, Maragheh, Iran.
| | - Mahnaz Nemati
- Amir Oncology Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Azam Bakhshandeh
- Department of Industrial Engineering and Management Systems, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran
| | - Arash Arashkia
- Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran
| | - Babak Negahdari
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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Jiang Y, Zhang H, Wang J, Chen J, Guo Z, Liu Y, Hua H. Exploiting RIG-I-like receptor pathway for cancer immunotherapy. J Hematol Oncol 2023; 16:8. [PMID: 36755342 PMCID: PMC9906624 DOI: 10.1186/s13045-023-01405-9] [Citation(s) in RCA: 61] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 01/30/2023] [Indexed: 02/10/2023] Open
Abstract
RIG-I-like receptors (RLRs) are intracellular pattern recognition receptors that detect viral or bacterial infection and induce host innate immune responses. The RLRs family comprises retinoic acid-inducible gene 1 (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2) that have distinctive features. These receptors not only recognize RNA intermediates from viruses and bacteria, but also interact with endogenous RNA such as the mislocalized mitochondrial RNA, the aberrantly reactivated repetitive or transposable elements in the human genome. Evasion of RLRs-mediated immune response may lead to sustained infection, defective host immunity and carcinogenesis. Therapeutic targeting RLRs may not only provoke anti-infection effects, but also induce anticancer immunity or sensitize "immune-cold" tumors to immune checkpoint blockade. In this review, we summarize the current knowledge of RLRs signaling and discuss the rationale for therapeutic targeting RLRs in cancer. We describe how RLRs can be activated by synthetic RNA, oncolytic viruses, viral mimicry and radio-chemotherapy, and how the RNA agonists of RLRs can be systemically delivered in vivo. The integration of RLRs agonism with RNA interference or CAR-T cells provides new dimensions that complement cancer immunotherapy. Moreover, we update the progress of recent clinical trials for cancer therapy involving RLRs activation and immune modulation. Further studies of the mechanisms underlying RLRs signaling will shed new light on the development of cancer therapeutics. Manipulation of RLRs signaling represents an opportunity for clinically relevant cancer therapy. Addressing the challenges in this field will help develop future generations of cancer immunotherapy.
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Affiliation(s)
- Yangfu Jiang
- Laboratory of Oncogene, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Hongying Zhang
- Laboratory of Oncogene, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jiao Wang
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
| | - Jinzhu Chen
- Laboratory of Oncogene, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Zeyu Guo
- Laboratory of Oncogene, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yongliang Liu
- Laboratory of Oncogene, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hui Hua
- Laboratory of Stem Cell Biology, West China Hospital, Sichuan University, Chengdu, 610041, China.
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11
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Han S, Chen X, Huang L. The tumor therapeutic potential of long non-coding RNA delivery and targeting. Acta Pharm Sin B 2022; 13:1371-1382. [PMID: 37139413 PMCID: PMC10149988 DOI: 10.1016/j.apsb.2022.12.005] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 10/25/2022] [Accepted: 11/11/2022] [Indexed: 12/15/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) is a type of RNA over 200 nt long without any protein coding ability, which has been investigated relating to crucial biological function in cells. There are many key lncRNAs in tumor/normal cells that serve as a biological marker or a new target for tumor treatment. However, compared to some small non-coding RNA, lncRNA-based drugs are limited in clinical application. Different from other non-coding RNA, like microRNAs, most lncRNAs have a high molecular weight and conserved secondary structure, making the delivery of lncRNAs more complex than the small non-coding RNAs. Considering that lncRNAs constitute the most abundant part of the mammalian genome, it is critical to further explore lncRNA delivery and the subsequent functional studies for potential clinical application. In this review, we will discuss the function and mechanism of lncRNAs in diseases, especially cancer, and different approaches for lncRNA transfection using multiple biomaterials.
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12
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Dhandapani RK, Gurusamy D, Palli SR. Protamine-Lipid-dsRNA Nanoparticles Improve RNAi Efficiency in the Fall Armyworm, Spodoptera frugiperda. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:6634-6643. [PMID: 35612305 DOI: 10.1021/acs.jafc.2c00901] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Developing safe and effective double-stranded RNA (dsRNA) delivery systems remains a major challenge for gene silencing, especially in lepidopteran insects. This study evaluated the protamine sulfate (PS)/lipid/dsRNA nanoparticle (NP) delivery system for RNA interference (RNAi) in cells and larvae of the fall armyworm (FAW), Spodoptera frugiperda, a major worldwide pest. A highly efficient gene delivery formulation was prepared using a cationic biopolymer, PS, and a cationic lipid, Cellfectin (CF), complexed with dsRNA. The NPs were prepared by a two-step self-assembly method. The formation of NPs was revealed by dynamic light scattering and transmission electron microscopy. The formation of CF/dsRNA/PS NPs was spherical in shape and size, ranging from 20 to 100 nm with a positive charge (+23.3 mV). Interestingly, prepared CF/dsRNA/PS NPs could protect dsRNA (95%) from nuclease degradation and thus significantly improve the stability of dsRNA. Formulations prepared by combining EGFP DNA with CF/PS increased transfection efficiency in Sf9 cells compared to PS/EGFP and CF/EGFP NPs. Also, the PS/CF/dsRNA NPs enhanced the endosomal escape for the intracellular delivery of dsRNA. The gene knockdown efficiency was assessed in Sf9 Luciferase (Luc) stable cells after a 72 h incubation with CF/dsRNA/PS, PS/dsRNA, CF/dsRNA, or naked dsRNA. Knockdown of the Luc gene was detected in CF/dsRNA/PS (76%) and PS/dsRNA (42.4%) not CF/dsRNA (19.5%) and naked dsRNA (10.3%) in Sf9 Luc cells. Moreover, CF/dsIAP/PS (25 μg of dsRNA targeting the inhibitor of apoptosis, IAP, gene of FAW) NPs showed knockdown of the IAP gene (39.5%) and mortality (55%) in FAW larvae. These results highlight the potential application of PS/lipid/dsRNA NPs for RNA-mediated control of insect pests.
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Affiliation(s)
| | - Dhandapani Gurusamy
- Department of Entomology, University of Kentucky, Lexington, Kentucky 40546, United States
| | - Subba Reddy Palli
- Department of Entomology, University of Kentucky, Lexington, Kentucky 40546, United States
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13
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Vetter VC, Wagner E. Targeting nucleic acid-based therapeutics to tumors: Challenges and strategies for polyplexes. J Control Release 2022; 346:110-135. [PMID: 35436520 DOI: 10.1016/j.jconrel.2022.04.013] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/07/2022] [Accepted: 04/10/2022] [Indexed: 12/18/2022]
Abstract
The current medical reality of cancer gene therapy is reflected by more than ten approved products on the global market, including oncolytic and other viral vectors and CAR T-cells as ex vivo gene-modified cell therapeutics. The development of synthetic antitumoral nucleic acid therapeutics has been proceeding at a lower but steady pace, fueled by a plethora of alternative nucleic acid platforms (from various antisense oligonucleotides, siRNA, microRNA, lncRNA, sgRNA, to larger mRNA and DNA) and several classes of physical and chemical delivery technologies. This review summarizes the challenges and strategies for tumor-targeted nucleic acid delivery. Focusing primarily on polyplexes (polycation complexes) as nanocarriers, delivery options across multiple barriers into tumor cells are illustrated.
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Affiliation(s)
- Victoria C Vetter
- Pharmaceutical Biotechnology, Center for System-based Drug Research, Ludwig-Maximilians-Universität, Munich 81377, Germany
| | - Ernst Wagner
- Pharmaceutical Biotechnology, Center for System-based Drug Research, Ludwig-Maximilians-Universität, Munich 81377, Germany; Center for NanoScience (CeNS), Ludwig-Maximilians-Universität, Munich 81377, Germany.
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14
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15
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Tenchov R, Bird R, Curtze AE, Zhou Q. Lipid Nanoparticles─From Liposomes to mRNA Vaccine Delivery, a Landscape of Research Diversity and Advancement. ACS NANO 2021; 15:16982-17015. [PMID: 34181394 DOI: 10.1021/acsnano.1c04996] [Citation(s) in RCA: 1018] [Impact Index Per Article: 254.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/18/2023]
Abstract
Lipid nanoparticles (LNPs) have emerged across the pharmaceutical industry as promising vehicles to deliver a variety of therapeutics. Currently in the spotlight as vital components of the COVID-19 mRNA vaccines, LNPs play a key role in effectively protecting and transporting mRNA to cells. Liposomes, an early version of LNPs, are a versatile nanomedicine delivery platform. A number of liposomal drugs have been approved and applied to medical practice. Subsequent generations of lipid nanocarriers, such as solid lipid nanoparticles, nanostructured lipid carriers, and cationic lipid-nucleic acid complexes, exhibit more complex architectures and enhanced physical stabilities. With their ability to encapsulate and deliver therapeutics to specific locations within the body and to release their contents at a desired time, LNPs provide a valuable platform for treatment of a variety of diseases. Here, we present a landscape of LNP-related scientific publications, including patents and journal articles, based on analysis of the CAS Content Collection, the largest human-curated collection of published scientific knowledge. Rising trends are identified, such as nanostructured lipid carriers and solid lipid nanoparticles becoming the preferred platforms for numerous formulations. Recent advancements in LNP formulations as drug delivery platforms, such as antitumor and nucleic acid therapeutics and vaccine delivery systems, are discussed. Challenges and growth opportunities are also evaluated in other areas, such as medical imaging, cosmetics, nutrition, and agrochemicals. This report is intended to serve as a useful resource for those interested in LNP nanotechnologies, their applications, and the global research effort for their development.
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Affiliation(s)
- Rumiana Tenchov
- CAS, a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | - Robert Bird
- CAS, a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | - Allison E Curtze
- CAS, a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | - Qiongqiong Zhou
- CAS, a division of the American Chemical Society, Columbus, Ohio 43210, United States
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16
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Szunerits S, Melinte S, Barras A, Pagneux Q, Voronova A, Abderrahmani A, Boukherroub R. The impact of chemical engineering and technological advances on managing diabetes: present and future concepts. Chem Soc Rev 2021; 50:2102-2146. [PMID: 33325917 DOI: 10.1039/c9cs00886a] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Monitoring blood glucose levels for diabetic patients is critical to achieve tight glycaemic control. As none of the current antidiabetic treatments restore lost functional β-cell mass in diabetic patients, insulin injections and the use of insulin pumps are most widely used in the management of glycaemia. The use of advanced and intelligent chemical engineering, together with the incorporation of micro- and nanotechnological-based processes have lately revolutionized diabetic management. The start of this concept goes back to 1974 with the description of an electrode that repeatedly measures the level of blood glucose and triggers insulin release from an infusion pump to enter the blood stream from a small reservoir upon need. Next to the insulin pumps, other drug delivery routes, including nasal, transdermal and buccal, are currently investigated. These processes necessitate competences from chemists, engineers-alike and innovative views of pharmacologists and diabetologists. Engineered micro and nanostructures hold a unique potential when it comes to drug delivery applications required for the treatment of diabetic patients. As the technical aspects of chemistry, biology and informatics on medicine are expanding fast, time has come to step back and to evaluate the impact of technology-driven chemistry on diabetics and how the bridges from research laboratories to market products are established. In this review, the large variety of therapeutic approaches proposed in the last five years for diabetic patients are discussed in an applied context. A survey of the state of the art of closed-loop insulin delivery strategies in response to blood glucose level fluctuation is provided together with insights into the emerging key technologies for diagnosis and drug development. Chemical engineering strategies centered on preserving and regenerating functional pancreatic β-cell mass are evoked in addition as they represent a permanent solution for diabetic patients.
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Affiliation(s)
- Sabine Szunerits
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520-IEMN, F-59000 Lille, France.
| | - Sorin Melinte
- Institute of Information and Communication Technologies, Electronics and Applied Mathematics, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium
| | - Alexandre Barras
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520-IEMN, F-59000 Lille, France.
| | - Quentin Pagneux
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520-IEMN, F-59000 Lille, France.
| | - Anna Voronova
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520-IEMN, F-59000 Lille, France.
| | - Amar Abderrahmani
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520-IEMN, F-59000 Lille, France.
| | - Rabah Boukherroub
- Univ. Lille, CNRS, Centrale Lille, Univ. Polytechnique Hauts-de-France, UMR 8520-IEMN, F-59000 Lille, France.
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17
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Jarzebska NT, Mellett M, Frei J, Kündig TM, Pascolo S. Protamine-Based Strategies for RNA Transfection. Pharmaceutics 2021; 13:pharmaceutics13060877. [PMID: 34198550 PMCID: PMC8231816 DOI: 10.3390/pharmaceutics13060877] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 05/28/2021] [Accepted: 06/03/2021] [Indexed: 01/04/2023] Open
Abstract
Protamine is a natural cationic peptide mixture mostly known as a drug for the neutralization of heparin and as a compound in formulations of slow-release insulin. Protamine is also used for cellular delivery of nucleic acids due to opposite charge-driven coupling. This year marks 60 years since the first use of Protamine as a transfection enhancement agent. Since then, Protamine has been broadly used as a stabilization agent for RNA delivery. It has also been involved in several compositions for RNA-based vaccinations in clinical development. Protamine stabilization of RNA shows double functionality: it not only protects RNA from degradation within biological systems, but also enhances penetration into cells. A Protamine-based RNA delivery system is a flexible and versatile platform that can be adjusted according to therapeutic goals: fused with targeting antibodies for precise delivery, digested into a cell penetrating peptide for better transfection efficiency or not-covalently mixed with functional polymers. This manuscript gives an overview of the strategies employed in protamine-based RNA delivery, including the optimization of the nucleic acid's stability and translational efficiency, as well as the regulation of its immunostimulatory properties from early studies to recent developments.
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Affiliation(s)
- Natalia Teresa Jarzebska
- Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091 Zürich, Switzerland; (N.T.J.); (M.M.); (J.F.); (T.M.K.)
- Faculty of Science, University of Zürich, 8091 Zürich, Switzerland
| | - Mark Mellett
- Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091 Zürich, Switzerland; (N.T.J.); (M.M.); (J.F.); (T.M.K.)
- Faculty of Medicine, University of Zürich, 8091 Zürich, Switzerland
| | - Julia Frei
- Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091 Zürich, Switzerland; (N.T.J.); (M.M.); (J.F.); (T.M.K.)
- Faculty of Medicine, University of Zürich, 8091 Zürich, Switzerland
| | - Thomas M. Kündig
- Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091 Zürich, Switzerland; (N.T.J.); (M.M.); (J.F.); (T.M.K.)
- Faculty of Medicine, University of Zürich, 8091 Zürich, Switzerland
| | - Steve Pascolo
- Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091 Zürich, Switzerland; (N.T.J.); (M.M.); (J.F.); (T.M.K.)
- Faculty of Medicine, University of Zürich, 8091 Zürich, Switzerland
- Correspondence:
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18
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Liu Y, Wu N. Progress of Nanotechnology in Diabetic Retinopathy Treatment. Int J Nanomedicine 2021; 16:1391-1403. [PMID: 33658779 PMCID: PMC7917322 DOI: 10.2147/ijn.s294807] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 02/05/2021] [Indexed: 12/16/2022] Open
Abstract
Diabetic retinopathy (DR) is a chronic diabetes complication that progressively manifests itself as blurred vision, eye floaters, distorted vision, and even partial or total loss of vision as a result of retinal detachment in severe cases. Clinically, patients who have undergone variations in the microcirculation of the ocular fundus are treated with laser photocoagulation to improve the circulation of retina; but for patients with macular edema, anti-vascular endothelial growth factor (anti-VEGF) drugs are generally injected to eliminate macular edema and improve vision. The worst cases are patients with fundus hemorrhage or proliferative vitreoretinopathy, for whom vitrectomy has been performed. At present, these clinical treatment methods have widely been used, providing satisfactory results. However, considering the low bioavailability and potential side effects of drugs and the inevitable risks in major surgery, DR prevention, and treatment as well as nerve tissue regeneration in the later stage have always been the focus of research. In recent years, nanotechnology has been increasingly applied in the medical field, leading to new ideas for DR treatment. This study aims to systematically review the research progress of nanotechnology in DR treatment.
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Affiliation(s)
- Yuxin Liu
- Student Affairs Department, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China
| | - Na Wu
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China
- Clinical Skills Practice Teaching Center, Shengjing Hospital of China Medical University, Shenyang, 110004, People’s Republic of China
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19
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Abstract
The major challenge for RNAi-based therapy is the fabrication of the delivery system that meet the requirement of clinical applicability. Liposome-derived nanoparticles (NPs) are one of the best investigated systems for in vivo siRNA delivery. In the recent years, we have successfully redesigned the conventional cationic liposomes into Liposome/Protamine/hyaluronic acid (LPH) NPs and Lipid-Calcium-Phosphate (LCP) NPs in order to increase the in vivo gene silencing effect and reduce the toxicity. Here we describe the preparation of LPH and LCP NPs loaded with siRNA, and characterization analysis including size distribution, trapping efficiency, and in vivo activity. This protocol could be used for in vivo delivery of siRNA to target genes in cancer cells.
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Affiliation(s)
- Yang Liu
- Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Irvine, CA, USA.
| | - Leaf Huang
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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20
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Zabel MD, Mollnow L, Bender H. siRNA Therapeutics for Protein Misfolding Diseases of the Central Nervous System. Methods Mol Biol 2021; 2282:377-394. [PMID: 33928585 DOI: 10.1007/978-1-0716-1298-9_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Nanoparticles have been used to deliver siRNA to tissues and cells to silence specific genes in diverse organisms. Research and clinical application of nanoparticles like liposomes for drug delivery requires targeting them to specific anatomic regions or cell types, while avoiding off-target effects or clearance by the liver, kidney, or the immune system. Delivery to the central nervous system (CNS) presents additional challenges to cross the blood-brain barrier (BBB) to specific cell types like neurons, astrocytes, or glia. Here, we describe the generation of three different liposomal siRNA delivery vehicles to the CNS using the thin film hydration method. Utilizing cationic or anionic liposomes protects the siRNA from serum nucleases and proteases en route. To deliver the siRNA specifically to the CNS, the liposomes are complexed to a peptide that acts as a neuronal address by binding to nicotinic acetylcholine receptors (nAchRs). When injected intravenously or instilled intranasally, these liposome-siRNA-peptide complexes (LSPCs) or peptide addressed liposome-encapsulated therapeutic siRNA (PALETS) resist serum degradation, effectively cross the BBB, and deliver siRNA to AchR-expressing cells to suppress protein expression in the CNS.
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Affiliation(s)
- Mark D Zabel
- Prion Research Center, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
| | - Luke Mollnow
- Prion Research Center, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA
| | - Heather Bender
- Prion Research Center, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA
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21
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Mukherjee MB, Mullick R, Reddy BU, Das S, Raichur AM. Galactose Functionalized Mesoporous Silica Nanoparticles As Delivery Vehicle in the Treatment of Hepatitis C Infection. ACS APPLIED BIO MATERIALS 2020; 3:7598-7610. [PMID: 35019500 DOI: 10.1021/acsabm.0c00814] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
DNA and RNA based antiviral strategies using nonviral vectors have shown better potential over the viral pathway due to the fewer chances of gene recombination and immunogenicity. In this work a mesoporous silica nanoparticle (MSN) based carrier system has been used for targeted delivery of shDNA molecule against the conserved 5'-untranslated region (UTR) in the RNA of a hepatitis C virus to inhibit its replication. The MSNs coated with amine and galactose could specifically target liver cells. Significant reduction (about 94%) of viral RNA level was achieved in HCV-JFH1 infectious cell culture compared to the control RNA levels directed the successful delivery and action of the shDNA. This study showed that Gal-AMSN can be used as a synthetic delivery vector to deliver the shDNA effectively for the treatment of HCV infection.
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Affiliation(s)
- Mousumi Beto Mukherjee
- Department of Materials Engineering, Indian Institute of Science, Bangalore 560012, India
| | - Ranajoy Mullick
- Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India
| | - B Uma Reddy
- Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India
| | - Saumitra Das
- Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India
| | - Ashok M Raichur
- Department of Materials Engineering, Indian Institute of Science, Bangalore 560012, India
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22
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Guevara ML, Persano F, Persano S. Advances in Lipid Nanoparticles for mRNA-Based Cancer Immunotherapy. Front Chem 2020; 8:589959. [PMID: 33195094 PMCID: PMC7645050 DOI: 10.3389/fchem.2020.589959] [Citation(s) in RCA: 166] [Impact Index Per Article: 33.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 09/16/2020] [Indexed: 12/29/2022] Open
Abstract
Over the past decade, messenger RNA (mRNA) has emerged as potent and flexible platform for the development of novel effective cancer immunotherapies. Advances in non-viral gene delivery technologies, especially the tremendous progress in lipid nanoparticles' manufacturing, have made possible the implementation of mRNA-based antitumor treatments. Several mRNA-based immunotherapies have demonstrated antitumor effect in preclinical and clinical studies, and marked successes have been achieved most notably by its implementation in therapeutic vaccines, cytokines therapies, checkpoint blockade and chimeric antigen receptor (CAR) cell therapy. In this review, we summarize recent advances in the development of lipid nanoparticles for mRNA-based immunotherapies and their applications in cancer treatment. Finally, we also highlight the variety of immunotherapeutic approaches through mRNA delivery and discuss the main factors affecting transfection efficiency and tropism of mRNA-loaded lipid nanoparticles in vivo.
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Affiliation(s)
- Maria L Guevara
- Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
| | - Francesca Persano
- Department Matematica e Fisica 'Ennio De Giorgi', Università del Salento, Lecce, Italy
| | - Stefano Persano
- Nanomaterials for Biomedical Applications, Istituto Italiano di Tecnologia (IIT), Genova, Italy
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23
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Abstract
Messenger RNA (mRNA) has immense potential for developing a wide range of therapies, including immunotherapy and protein replacement. As mRNA presents no risk of integration into the host genome and does not require nuclear entry for transfection, which allows protein production even in nondividing cells, mRNA-based approaches can be envisioned as safe and practical therapeutic strategies. Nevertheless, mRNA presents unfavorable characteristics, such as large size, immunogenicity, limited cellular uptake, and sensitivity to enzymatic degradation, which hinder its use as a therapeutic agent. While mRNA stability and immunogenicity have been ameliorated by direct modifications on the mRNA structure, further improvements in mRNA delivery are still needed for promoting its activity in biological settings. In this regard, nanomedicine has shown the ability for spatiotemporally controlling the function of a myriad of bioactive agents in vivo. Direct engineering of nanomedicine structures for loading, protecting, and releasing mRNA and navigating in biological environments can then be applied for promoting mRNA translation toward the development of effective treatments. Here, we review recent approaches aimed at enhancing mRNA function and its delivery through nanomedicines, with particular emphasis on their applications and eventual clinical translation.
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Affiliation(s)
- Satoshi Uchida
- Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.,Innovation Center of NanoMedicine, Kawasaki Institute of Industrial Promotion, 3-25-14, Tonomachi, Kawasaki 210-0821, Japan
| | - Federico Perche
- Centre de Biophysique Moléculaire, UPR4301 CNRS Rue Charles Sadron Orléans, Orléans 45071 Cedex 02, France
| | - Chantal Pichon
- Centre de Biophysique Moléculaire, UPR4301 CNRS Rue Charles Sadron Orléans, Orléans 45071 Cedex 02, France.,Faculty of Sciences and Techniques, University of Orléans, Orléans 45071 Cedex 02, France
| | - Horacio Cabral
- Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.,Innovation Center of NanoMedicine, Kawasaki Institute of Industrial Promotion, 3-25-14, Tonomachi, Kawasaki 210-0821, Japan
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24
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Hybrid Biopolymer and Lipid Nanoparticles with Improved Transfection Efficacy for mRNA. Cells 2020; 9:cells9092034. [PMID: 32899484 PMCID: PMC7563888 DOI: 10.3390/cells9092034] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 09/01/2020] [Accepted: 09/02/2020] [Indexed: 12/11/2022] Open
Abstract
Hybrid nanoparticles from lipidic and polymeric components were assembled to serve as vehicles for the transfection of messenger RNA (mRNA) using different portions of the cationic lipid DOTAP (1,2-Dioleoyl-3-trimethylammonium-propane) and the cationic biopolymer protamine as model systems. Two different sequential assembly approaches in comparison with a direct single-step protocol were applied, and molecular organization in correlation with biological activity of the resulting nanoparticle systems was investigated. Differences in the structure of the nanoparticles were revealed by thorough physicochemical characterization including small angle neutron scattering (SANS), small angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). All hybrid systems, combining lipid and polymer, displayed significantly increased transfection in comparison to lipid/mRNA and polymer/mRNA particles alone. For the hybrid nanoparticles, characteristic differences regarding the internal organization, release characteristics, and activity were determined depending on the assembly route. The systems with the highest transfection efficacy were characterized by a heterogenous internal organization, accompanied by facilitated release. Such a system could be best obtained by the single step protocol, starting with a lipid and polymer mixture for nanoparticle formation.
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25
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Salvioni L, Zuppone S, Andreata F, Monieri M, Mazzucchelli S, Di Carlo C, Morelli L, Cordiglieri C, Donnici L, De Francesco R, Corsi F, Prosperi D, Vago R, Colombo M. Nanoparticle‐Mediated Suicide Gene Therapy for Triple Negative Breast Cancer Treatment. ADVANCED THERAPEUTICS 2020. [DOI: 10.1002/adtp.202000007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Lucia Salvioni
- NanoBioLabDepartment of Biotechnology and BiosciencesUniversity of Milano‐Bicocca Piazza della Scienza 2 Milan 20126 Italy
| | - Stefania Zuppone
- Urologic Research InstituteDivision of Experimental OncologyIRCCS San Raffaele Scientific Institute via Olgettina 60 Milan 20132 Italy
| | - Francesco Andreata
- Nanomedicine LaboratoryDepartment of Biomedical and Clinical Sciences “L. Sacco”Università degli Studi di Milano via G. B. Grassi, 74 Milan 20157 Italy
| | - Matteo Monieri
- Nanomedicine LaboratoryDepartment of Biomedical and Clinical Sciences “L. Sacco”Università degli Studi di Milano via G. B. Grassi, 74 Milan 20157 Italy
| | - Serena Mazzucchelli
- Nanomedicine LaboratoryDepartment of Biomedical and Clinical Sciences “L. Sacco”Università degli Studi di Milano via G. B. Grassi, 74 Milan 20157 Italy
| | - Caterina Di Carlo
- NanoBioLabDepartment of Biotechnology and BiosciencesUniversity of Milano‐Bicocca Piazza della Scienza 2 Milan 20126 Italy
| | - Lucia Morelli
- NanoBioLabDepartment of Biotechnology and BiosciencesUniversity of Milano‐Bicocca Piazza della Scienza 2 Milan 20126 Italy
| | - Chiara Cordiglieri
- INGM – Istituto Nazionale di Genetica Molecolare “Romeo ed Enrica Invernizzi,” Via Francesco Sforza 35 Milan 20122 Italy
| | - Lorena Donnici
- INGM – Istituto Nazionale di Genetica Molecolare “Romeo ed Enrica Invernizzi,” Via Francesco Sforza 35 Milan 20122 Italy
| | - Raffaele De Francesco
- INGM – Istituto Nazionale di Genetica Molecolare “Romeo ed Enrica Invernizzi,” Via Francesco Sforza 35 Milan 20122 Italy
- Department of Pharmacological and Biomolecular Sciences via Balzaretti 9 Milano 20133 Italy
| | - Fabio Corsi
- Nanomedicine LaboratoryDepartment of Biomedical and Clinical Sciences “L. Sacco”Università degli Studi di Milano via G. B. Grassi, 74 Milan 20157 Italy
- Breast UnitSurgery DepartmentICS Maugeri IRCCS via S. Maugeri 10 Pavia 27100 Italy
| | - Davide Prosperi
- NanoBioLabDepartment of Biotechnology and BiosciencesUniversity of Milano‐Bicocca Piazza della Scienza 2 Milan 20126 Italy
- Breast UnitSurgery DepartmentICS Maugeri IRCCS via S. Maugeri 10 Pavia 27100 Italy
| | - Riccardo Vago
- Urologic Research InstituteDivision of Experimental OncologyIRCCS San Raffaele Scientific Institute via Olgettina 60 Milan 20132 Italy
- Università Vita‐Salute San Raffaele via Olgettina, 58 Milan 20132 Italy
| | - Miriam Colombo
- NanoBioLabDepartment of Biotechnology and BiosciencesUniversity of Milano‐Bicocca Piazza della Scienza 2 Milan 20126 Italy
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26
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Chen H, Fan X, Zhao Y, Zhi D, Cui S, Zhang E, Lan H, Du J, Zhang Z, Zhang S, Zhen Y. Stimuli-Responsive Polysaccharide Enveloped Liposome for Targeting and Penetrating Delivery of survivin-shRNA into Breast Tumor. ACS APPLIED MATERIALS & INTERFACES 2020; 12:22074-22087. [PMID: 32083833 DOI: 10.1021/acsami.9b22440] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
Silencing the inhibitor of apoptosis (IAP) by RNAi is a promising method for tumor therapy. One of the major challenges lies in how to sequentially overcome the system barriers in the course of the tumor targeting delivery, especially in the tumor accumulation and penetration. Herein we developed a novel stimuli-responsive polysaccharide enveloped liposome carrier, which was constructed by layer-by-layer depositing redox-sensitive amphiphilic chitosan (CS) and hyaluronic acid (HA) onto the liposome and then loading IAP inhibitor survivin-shRNA gene and permeation promoter hyaluronidase (HAase) sequentially. The as-prepared HA/HAase/CS/liposome/shRNA (HCLR) nanocarrier was verified to be stable in blood circulation due to the negative charged HA shield. The tumor targeting recognition and the enhanced tumor accumulation of HCLR were visualized by fluorescence resonance energy transfer (FRET) and in vivo fluorescence biodistribution. The deshielding of HA and the protonizing of CS in slightly acidic tumor extracellular pH environment (pHe, 6.8-6.5) were demonstrated by ζ potential change from -23.1 to 29.9 mV. The pHe-responsive HAase release was confirmed in the tumor extracellular mimicking environments, and the intratumoral biodistribution showed that the tumor penetration of HCLR was improved. The cell uptake of HCLR in pHe environment was significantly enhanced compared with that in physiological pH environment. The increased shRNA release of HCLR was approved in 10 mM glutathione (GSH) and tumor cells. Surprisingly, HCLR suppressed the tumor growth markedly through survivin silencing and meanwhile maintained low toxicity to mice. This study indicates that the novel polysaccharide enveloped HCLR is promising in clinical translation, thanks to the stimuli-triggered tumor accumulation, tumor penetration, cell uptake, and intracellular gene release.
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Affiliation(s)
- Huiying Chen
- Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Science, Dalian Minzu University, 18 Liaohe West Road, Dalian 116600, Liaoning Province People's Republic of China
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Ganjingzi District, Dalian 116024, Liaoning Province People's Republic of China
| | - Xuefeng Fan
- Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Science, Dalian Minzu University, 18 Liaohe West Road, Dalian 116600, Liaoning Province People's Republic of China
| | - Yinan Zhao
- Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Science, Dalian Minzu University, 18 Liaohe West Road, Dalian 116600, Liaoning Province People's Republic of China
| | - Defu Zhi
- Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Science, Dalian Minzu University, 18 Liaohe West Road, Dalian 116600, Liaoning Province People's Republic of China
| | - Shaohui Cui
- Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Science, Dalian Minzu University, 18 Liaohe West Road, Dalian 116600, Liaoning Province People's Republic of China
| | - Enxia Zhang
- College of Pharmacy, Dalian Medical University, 9 West Section Lvshun South Road, Dalian 116044, Liaoning Province People's Republic of China
| | - Haoming Lan
- Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Science, Dalian Minzu University, 18 Liaohe West Road, Dalian 116600, Liaoning Province People's Republic of China
| | - Jianjun Du
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Ganjingzi District, Dalian 116024, Liaoning Province People's Republic of China
| | - Zhen Zhang
- State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Ganjingzi District, Dalian 116024, Liaoning Province People's Republic of China
| | - Shubiao Zhang
- Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, College of Life Science, Dalian Minzu University, 18 Liaohe West Road, Dalian 116600, Liaoning Province People's Republic of China
| | - Yuhong Zhen
- College of Pharmacy, Dalian Medical University, 9 West Section Lvshun South Road, Dalian 116044, Liaoning Province People's Republic of China
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Abstract
Current conventional endoscopes have restricted the accuracy of treatment delivery and monitoring. Over the past decade, there have been major developments in nanotechnology and light triggered therapy, potentially allowing a better detection of challenging lesions and targeted treatment of malignancies in the gastrointestinal tract. Theranostics is a developing form of personalized medicine because it combines diagnosis and targeted treatment delivered in one step using advances in nanotechnology. This review describes the light-triggered therapies (including photodynamic, photothermal, and photoimmunotherapies), nanotechnological advances with nanopowder, nanostent, nanogels, and nanoparticles, enhancements brought to endoscopic ultrasound, in addition to experimental endoscopic techniques, combining both enhanced diagnoses and therapies, including a developed prototype of a “smart” multifunctional endoscope for localized colorectal cancer, near-infrared laser endoscope targeting the gastrointestinal stromal tumors, the concept of endocapsule for obscure gastrointestinal bleed, and a proof-of-concept therapeutic capsule using ultrasound-mediated targeted drug delivery. Hence, the following term has been proposed encompassing these technologies: “Theranostic gastrointestinal endoscopy.” Future efforts for integration of these technologies into clinical practice would be directed toward translational and clinical trials translating into a more personalized and interdisciplinary diagnosis and treatment, shorter procedural time, higher precision, higher cost-effectiveness, and less need for repetitive procedures.
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Fukushige K, Tagami T, Naito M, Goto E, Hirai S, Hatayama N, Yokota H, Yasui T, Baba Y, Ozeki T. Developing spray-freeze-dried particles containing a hyaluronic acid-coated liposome-protamine-DNA complex for pulmonary inhalation. Int J Pharm 2020; 583:119338. [PMID: 32311468 DOI: 10.1016/j.ijpharm.2020.119338] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 04/09/2020] [Accepted: 04/14/2020] [Indexed: 01/09/2023]
Abstract
The liposome-protamine-DNA complex (LPD) is an effective cationic carrier of various nucleic acid constructs such as plasmid DNA and small interfering RNA (siRNA). Hyaluronic acid coated on LPD (LPDH) reduces cytotoxicity and maintains the silencing effect of LPD-encapsulated siRNA. Herein, we aim to develop LPD- or LPDH-containing spray-freeze-dried particles (SFDPs) for therapeutic delivery of siRNA to the lungs. LPD- or LPDH-containing SFDPs (LPD- or LPDH-SFDPs) were synthesized and their structure and function as gene carriers were evaluated using physical and biological methods. The particle size of LPDH, but not of LPD, was constant after re-dispersal from the SFDPs and the amount of siRNA encapsulated in LPDH was larger than that in LPD after re-dispersal from the SFDPs. The in vitro pulmonary inhalation properties of LPDH-SFDPs and LPD-SFDPs were almost the same. The cytotoxicity of LPDH-SFDPs in human umbilical vein endothelial cells (HUVEC) was greatly decreased compared with that of LPD-SFDPs. In addition, Bcl-2 siRNA in LPDH-SFDPs had a significant gene silencing effect in human lung cancer cells (A549), whereas Bcl-2 siRNA in LPD-SFDPs had little effect. These results indicate that compared with LPD, LPDH is more useful for developing SFDPs for siRNA pulmonary inhalation.
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Affiliation(s)
- Kaori Fukushige
- Department of Anatomy, School of Medicine, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan; Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
| | - Tatsuaki Tagami
- Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan
| | - Munekazu Naito
- Department of Anatomy, School of Medicine, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan
| | - Eiichi Goto
- Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan
| | - Shuichi Hirai
- Department of Anatomy, School of Medicine, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan
| | - Naoyuki Hatayama
- Department of Anatomy, School of Medicine, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan
| | - Hiroki Yokota
- Department of Anatomy, School of Medicine, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan
| | - Takao Yasui
- Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8603, Japan
| | - Yoshinobu Baba
- Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8603, Japan
| | - Tetsuya Ozeki
- Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan
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Xue Y, Feng J, Liu Y, Che J, Bai G, Dong X, Wu F, Jin T. A Synthetic Carrier of Nucleic Acids Structured as a Neutral Phospholipid Envelope Tightly Assembled on Polyplex Surface. Adv Healthc Mater 2020; 9:e1901705. [PMID: 31977157 DOI: 10.1002/adhm.201901705] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 01/05/2020] [Indexed: 12/24/2022]
Abstract
Synthetic carriers of nucleic acids remain inefficient for practical applications due to their insufficient functions as compared with viral vectors developed by evolution. Here, a synthetic carrier is designed to structurally mimic lentivirus, a widely-used viral vector in therapeutic developments, for its neutral phospholipid membrane tightly anchored on the surface of a packed nucleic acid core. Unlike the reported lipopolyplexes of which the surface membrane around the nucleic acid core is formed from charged lipids, the stable attachment of the neutral lipids to each polyplex core in the present system is achieved through preadsorbed micelles of multicarboxyl amphiphilic molecules as lipid bilayer anchors. The adsorbed micelles are under a tension of deformation due to the electrostatic attraction of the head groups to the cationic surface and their "thermodynamic responsibility" to cover the hydrophobic tails in water. When liposomes of neutral phospholipids approach, the hydrophobic tail groups of the adsorbed micelles may insert into the lipid bilayer matrix to induce them to fuse around polyplex and relieve the thermodynamic tension. The formed neutral phospholipid membrane may encapsulate the polyplex core stably, prevent siRNA from prephagocytic leaking and degrading, and immobilize functional agents with increased capacity.
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Affiliation(s)
- Yonger Xue
- Center for BioDelivery SciencesSchool of PharmacyShanghai Jiao Tong University 800 Dongchuan Rd Shanghai 200240 P. R. China
| | - Jia Feng
- Center for BioDelivery SciencesSchool of PharmacyShanghai Jiao Tong University 800 Dongchuan Rd Shanghai 200240 P. R. China
| | - Yilei Liu
- Center for BioDelivery SciencesSchool of PharmacyShanghai Jiao Tong University 800 Dongchuan Rd Shanghai 200240 P. R. China
| | - Junyi Che
- Center for BioDelivery SciencesSchool of PharmacyShanghai Jiao Tong University 800 Dongchuan Rd Shanghai 200240 P. R. China
| | - Guang Bai
- Center for BioDelivery SciencesSchool of PharmacyShanghai Jiao Tong University 800 Dongchuan Rd Shanghai 200240 P. R. China
| | - Xiaotao Dong
- Center for BioDelivery SciencesSchool of PharmacyShanghai Jiao Tong University 800 Dongchuan Rd Shanghai 200240 P. R. China
| | - Fei Wu
- Center for BioDelivery SciencesSchool of PharmacyShanghai Jiao Tong University 800 Dongchuan Rd Shanghai 200240 P. R. China
| | - Tuo Jin
- Center for BioDelivery SciencesSchool of PharmacyShanghai Jiao Tong University 800 Dongchuan Rd Shanghai 200240 P. R. China
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30
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Vijayan V, Mohapatra A, Uthaman S, Park IK. Recent Advances in Nanovaccines Using Biomimetic Immunomodulatory Materials. Pharmaceutics 2019; 11:E534. [PMID: 31615112 PMCID: PMC6835828 DOI: 10.3390/pharmaceutics11100534] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 10/09/2019] [Accepted: 10/11/2019] [Indexed: 12/28/2022] Open
Abstract
The development of vaccines plays a vital role in the effective control of several fatal diseases. However, effective prophylactic and therapeutic vaccines have yet to be developed for completely curing deadly diseases, such as cancer, malaria, HIV, and serious microbial infections. Thus, suitable vaccine candidates need to be designed to elicit appropriate immune responses. Nanotechnology has been found to play a unique role in the design of vaccines, providing them with enhanced specificity and potency. Nano-scaled materials, such as virus-like particles, liposomes, polymeric nanoparticles (NPs), and protein NPs, have received considerable attention over the past decade as potential carriers for the delivery of vaccine antigens and adjuvants, due to their beneficial advantages, like improved antigen stability, targeted delivery, and long-time release, for which antigens/adjuvants are either encapsulated within, or decorated on, the NP surface. Flexibility in the design of nanomedicine allows for the programming of immune responses, thereby addressing the many challenges encountered in vaccine development. Biomimetic NPs have emerged as innovative natural mimicking biosystems that can be used for a wide range of biomedical applications. In this review, we discuss the recent advances in biomimetic nanovaccines, and their use in anti-bacterial therapy, anti-HIV therapy, anti-malarial therapy, anti-melittin therapy, and anti-tumor immunity.
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Affiliation(s)
- Veena Vijayan
- Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 58128, Korea.
| | - Adityanarayan Mohapatra
- Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 58128, Korea.
| | - Saji Uthaman
- Department of Polymer Science and Engineering, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea.
| | - In-Kyu Park
- Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 58128, Korea.
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31
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Scheetz L, Park KS, Li Q, Lowenstein PR, Castro MG, Schwendeman A, Moon JJ. Engineering patient-specific cancer immunotherapies. Nat Biomed Eng 2019; 3:768-782. [PMID: 31406259 PMCID: PMC6783331 DOI: 10.1038/s41551-019-0436-x] [Citation(s) in RCA: 139] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 07/03/2019] [Indexed: 02/06/2023]
Abstract
Research into the immunological processes implicated in cancer has yielded a basis for the range of immunotherapies that are now considered the fourth pillar of cancer treatment (alongside surgery, radiotherapy and chemotherapy). For some aggressive cancers, such as advanced non-small-cell lung carcinoma, combination immunotherapies have resulted in unprecedented treatment efficacy for responding patients, and have become frontline therapies. Individualized immunotherapy, enabled by the identification of patient-specific mutations, neoantigens and biomarkers, and facilitated by advances in genomics and proteomics, promises to broaden the responder patient population. In this Perspective, we give an overview of immunotherapies leveraging engineering approaches, including the design of biomaterials, delivery strategies and nanotechnology solutions, for the realization of individualized cancer treatments such as nanoparticle vaccines customized with neoantigens, cell therapies based on patient-derived dendritic cells and T cells, and combinations of theranostic strategies. Developments in precision cancer immunotherapy will increasingly rely on the adoption of engineering principles.
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Affiliation(s)
- Lindsay Scheetz
- Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA
- Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA
| | - Kyung Soo Park
- Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
| | - Qiao Li
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Pedro R Lowenstein
- Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA
- Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA
| | - Maria G Castro
- Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA
- Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA
| | - Anna Schwendeman
- Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA
- Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA
| | - James J Moon
- Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.
- Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
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32
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Meng L, Liu X, Wang Y, Zhang W, Zhou W, Cai F, Li F, Wu J, Xu L, Niu L, Zheng H. Sonoporation of Cells by a Parallel Stable Cavitation Microbubble Array. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2019; 6:1900557. [PMID: 31508275 PMCID: PMC6724477 DOI: 10.1002/advs.201900557] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 05/15/2019] [Indexed: 05/06/2023]
Abstract
Sonoporation is a targeted drug delivery technique that employs cavitation microbubbles to generate transient pores in the cell membrane, allowing foreign substances to enter cells by passing through the pores. Due to the broad size distribution of microbubbles, cavitation events appear to be a random process, making it difficult to achieve controllable and efficient sonoporation. In this work a technique is reported using a microfluidic device that enables in parallel modulation of membrane permeability by an oscillating microbubble array. Multirectangular channels of uniform size are created at the sidewall to generate an array of monodispersed microbubbles, which oscillate with almost the same amplitude and resonant frequency, ensuring homogeneous sonoporation with high efficacy. Stable harmonic and high harmonic signals emitted by individual oscillating microbubbles are detected by a laser Doppler vibrometer, which indicates stable cavitation occurred. Under the influence of the acoustic radiation forces induced by the oscillating microbubble, single cells can be trapped at an oscillating microbubble surface. The sonoporation of single cells is directly influenced by the individual oscillating microbubble. The parallel sonoporation of multiple cells is achieved with an efficiency of 96.6 ± 1.74% at an acoustic pressure as low as 41.7 kPa.
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Affiliation(s)
- Long Meng
- Paul C. Lauterbur Research Center for Biomedical ImagingInstitute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen518055China
- CAS Key Laboratory of Health InformaticsShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen518055China
| | - Xiufang Liu
- Paul C. Lauterbur Research Center for Biomedical ImagingInstitute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen518055China
- Sino‐Dutch Biomedical and Information Engineering SchoolNortheastern University195 Innovation roadShenyang110169China
| | - Yuchen Wang
- Paul C. Lauterbur Research Center for Biomedical ImagingInstitute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen518055China
- Faculty of Engineering and ArchitectureGhent UniversityJozef Plateaustraat 229000GhentBelgium
| | - Wenjun Zhang
- Paul C. Lauterbur Research Center for Biomedical ImagingInstitute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen518055China
- Key Laboratory of E&MMinistry of Education & Zhejiang ProvinceZhejiang University of Technology18 Chaowang RoadHangzhou310014China
| | - Wei Zhou
- Paul C. Lauterbur Research Center for Biomedical ImagingInstitute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen518055China
| | - Feiyan Cai
- Paul C. Lauterbur Research Center for Biomedical ImagingInstitute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen518055China
- CAS Key Laboratory of Health InformaticsShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen518055China
| | - Fei Li
- Paul C. Lauterbur Research Center for Biomedical ImagingInstitute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen518055China
- CAS Key Laboratory of Health InformaticsShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen518055China
| | - Junru Wu
- Department of PhysicsUniversity of VermontBurlingtonVT05405USA
| | - Lisheng Xu
- Sino‐Dutch Biomedical and Information Engineering SchoolNortheastern University195 Innovation roadShenyang110169China
| | - Lili Niu
- Paul C. Lauterbur Research Center for Biomedical ImagingInstitute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen518055China
- CAS Key Laboratory of Health InformaticsShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen518055China
| | - Hairong Zheng
- Paul C. Lauterbur Research Center for Biomedical ImagingInstitute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen518055China
- CAS Key Laboratory of Health InformaticsShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen518055China
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33
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Sahle FF, Kim S, Niloy KK, Tahia F, Fili CV, Cooper E, Hamilton DJ, Lowe TL. Nanotechnology in regenerative ophthalmology. Adv Drug Deliv Rev 2019; 148:290-307. [PMID: 31707052 PMCID: PMC7474549 DOI: 10.1016/j.addr.2019.10.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 10/29/2019] [Accepted: 10/30/2019] [Indexed: 12/18/2022]
Abstract
In recent years, regenerative medicine is gaining momentum and is giving hopes for restoring function of diseased, damaged, and aged tissues and organs and nanotechnology is serving as a catalyst. In the ophthalmology field, various types of allogenic and autologous stem cells have been investigated to treat some ocular diseases due to age-related macular degeneration, glaucoma, retinitis pigmentosa, diabetic retinopathy, and corneal and lens traumas. Nanomaterials have been utilized directly as nanoscaffolds for these stem cells to promote their adhesion, proliferation and differentiation or indirectly as vectors for various genes, tissue growth factors, cytokines and immunosuppressants to facilitate cell reprogramming or ocular tissue regeneration. In this review, we reviewed various nanomaterials used for retina, cornea, and lens regenerations, and discussed the current status and future perspectives of nanotechnology in tracking cells in the eye and personalized regenerative ophthalmology. The purpose of this review is to provide comprehensive and timely insights on the emerging field of nanotechnology for ocular tissue engineering and regeneration.
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Affiliation(s)
- Fitsum Feleke Sahle
- Department of Pharmaceutical Sciences, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA
| | - Sangyoon Kim
- Department of Pharmaceutical Sciences, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA
| | - Kumar Kulldeep Niloy
- Department of Pharmaceutical Sciences, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA
| | - Faiza Tahia
- Department of Pharmaceutical Sciences, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA
| | - Cameron V Fili
- Department of Comparative Medicine, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA
| | - Emily Cooper
- Department of Pharmaceutical Sciences, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA
| | - David J Hamilton
- Department of Comparative Medicine, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA
| | - Tao L Lowe
- Department of Pharmaceutical Sciences, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA.
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34
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Abstract
RNA interference is a relatively new tool used to silence specific genes in diverse biological systems. The development of this promising new technique for research and therapeutic use in studying and treating neurological diseases has been hampered by the lack of an efficient way to deliver siRNA transvascularly across the blood-brain barrier (BBB) to the central nervous system (CNS). Here we describe the generation of three different liposomal siRNA delivery vehicles to the CNS using the thin film hydration method. Utilizing cationic or anionic liposomes protects the siRNA from serum nucleases and proteases en route. To deliver the siRNA specifically to the CNS, the liposomes are complexed to a peptide that acts as a neuronal address by binding to nicotinic acetylcholine receptors (nAchRs). When injected intravenously, these liposome-siRNA-peptide complexes (LSPCs) or peptide addressed liposome encapsulated therapeutic siRNA (PALETS) resist serum degradation, effectively cross the BBB and deliver siRNA to AchR-expressing cells to suppress protein expression in the CNS.
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35
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Zhang M, Lemay SG. Interaction of Anionic Bulk Nanobubbles with Cationic Liposomes: Evidence for Reentrant Condensation. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2019; 35:4146-4151. [PMID: 30811209 PMCID: PMC6427481 DOI: 10.1021/acs.langmuir.8b03927] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Revised: 02/25/2019] [Indexed: 06/09/2023]
Abstract
We investigated the interaction of bulk nanobubbles with cationic liposomes composed of 1,2-dioleoyl- sn-glycero-3-ethylphosphocholine and anionic liposomes assembled from 1-palmitoyl-2-oleoyl- sn-glycero-3-phospho-(1'- rac-glycerol). We employed dynamic light scattering and fluorescence microscopy to investigate both the hydrodynamic and electrophoretic properties of the nanobubble/liposome complexes. These optical techniques permit direct visualization of structural changes as a function of the bubble/liposome ratio. We observed reentrant condensation with cationic liposomes and gas nucleation with anionic liposomes. This is the first report of charge inversion and reentrant condensation of cationic liposomes induced by bulk nanobubbles.
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Affiliation(s)
- Minmin Zhang
- MESA+ Institute for Nanotechnology
& Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands
| | - Serge G. Lemay
- MESA+ Institute for Nanotechnology
& Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands
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36
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Abstract
Inherited retinal degeneration (IRD), a group of rare retinal diseases that primarily lead to the progressive loss of retinal photoreceptor cells, can be inherited in all modes of inheritance: autosomal dominant (AD), autosomal recessive (AR), X-linked (XL), and mitochondrial. Based on the pattern of inheritance of the dystrophy, retinal gene therapy has 2 main strategies. AR, XL, and AD IRDs with haploinsufficiency can be treated by inserting a functional copy of the gene using either viral or nonviral vectors (gene augmentation). Different types of viral vectors and nonviral vectors are used to transfer plasmid DNA both in vitro and in vivo. AD IRDs with gain-of-function mutations or dominant-negative mutations can be treated by disrupting the mutant allele with (and occasionally without) gene augmentation. This review article aims to provide an overview of ocular gene therapy for treating IRDs using gene augmentation with viral or nonviral vectors or gene disruption through different gene-editing tools, especially with the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system.
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Affiliation(s)
- Amirmohsen Arbabi
- Department of Ophthalmology, USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Amelia Liu
- Department of Ophthalmology, USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Hossein Ameri
- Department of Ophthalmology, USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California
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37
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Abstract
Calpain is an intracellular Ca2+-dependent non-lysosomal cysteine protease expressed ubiquitously in mammals. In endothelial cells, dysregulation of calpain has been shown to be involved in a wide variety of pathological conditions such as angiogenesis, vascular inflammation, and diabetes. Cell- or tissue-targeted in vivo delivery of small interfering RNA (siRNA) is a powerful research tool in the analysis of protein function and has been proposed as an attractive therapeutic modality that is applicable against a large number of human diseases including cancer. In this chapter we describe a method to knockdown calpain 1 in mouse pulmonary vascular endothelium using delivery of siRNA/cationic liposome complex. This technique results in a greater than 80% reduction in calpain 1 protein levels 48 h after a single i.v. injection of calpain 1 siRNA (0.5 mg siRNA/kg)/cationic liposome complex. We also describe confocal imaging to verify the loss of calpain 1 expression in pulmonary microvessel endothelial cells and application of this technique in the mouse model of ventilator-induced lung injury.
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Affiliation(s)
- Xiaoqian Liu
- Department of Anesthesiology, University of Illinois College of Medicine, Chicago, IL, USA
| | - Guochang Hu
- Department of Anesthesiology, University of Illinois College of Medicine, Chicago, IL, USA.
- Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL, USA.
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Core-Shell Nanoencapsulation of α-Tocopherol by Blending Sodium Oleate and Rebaudioside A: Preparation, Characterization, and Antioxidant Activity. Molecules 2018; 23:molecules23123183. [PMID: 30513920 PMCID: PMC6321206 DOI: 10.3390/molecules23123183] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 11/28/2018] [Accepted: 12/01/2018] [Indexed: 02/07/2023] Open
Abstract
Nanoencapsulation of α-tocopherol (α-TOC) by blending sodium oleate (NaOl) and rebaudioside A (RebA) was successfully prepared by self-assembly method under mild conditions. The optimized nanoemulsion showed the loading capacity of α-TOC was 30 wt% of sodium oleate. FTIR analysis suggested that hydrogen bonds and hydrophobic interactions were the major forces in α-TOC-NaOl/RebA complexes that were spherical and possessed well-distinguishable core-shell structures. The freeze-dried α-TOC-NaOl/RebA complexes had great stability under ambient conditions. The release profile of α-TOC showed a first-order kinetics reaching around 67.9% after 90 h at 25 °C. Nanoencapsulation improved dispersibility and greatly increased the antioxidant activity of α-TOC. Therefore, the stable α-TOC-NaOl/RebA core-shell complexes prepared from “generally recognized as safe” (GRAS) ingredients have great potential to supplement α-TOC in food and cosmetic products.
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Hobernik D, Bros M. DNA Vaccines-How Far From Clinical Use? Int J Mol Sci 2018; 19:ijms19113605. [PMID: 30445702 PMCID: PMC6274812 DOI: 10.3390/ijms19113605] [Citation(s) in RCA: 323] [Impact Index Per Article: 46.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 11/07/2018] [Accepted: 11/09/2018] [Indexed: 12/12/2022] Open
Abstract
Two decades ago successful transfection of antigen presenting cells (APC) in vivo was demonstrated which resulted in the induction of primary adaptive immune responses. Due to the good biocompatibility of plasmid DNA, their cost-efficient production and long shelf life, many researchers aimed to develop DNA vaccine-based immunotherapeutic strategies for treatment of infections and cancer, but also autoimmune diseases and allergies. This review aims to summarize our current knowledge on the course of action of DNA vaccines, and which factors are responsible for the poor immunogenicity in human so far. Important optimization steps that improve DNA transfection efficiency comprise the introduction of DNA-complexing nano-carriers aimed to prevent extracellular DNA degradation, enabling APC targeting, and enhanced endo/lysosomal escape of DNA. Attachment of virus-derived nuclear localization sequences facilitates nuclear entry of DNA. Improvements in DNA vaccine design include the use of APC-specific promotors for transcriptional targeting, the arrangement of multiple antigen sequences, the co-delivery of molecular adjuvants to prevent tolerance induction, and strategies to circumvent potential inhibitory effects of the vector backbone. Successful clinical use of DNA vaccines may require combined employment of all of these parameters, and combination treatment with additional drugs.
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Affiliation(s)
- Dominika Hobernik
- Department of Dermatology, University Medical Center, 55131 Mainz, Germany.
| | - Matthias Bros
- Department of Dermatology, University Medical Center, 55131 Mainz, Germany.
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40
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Liang T, Yao Z, Ding J, Min Q, Jiang L, Zhu JJ. Cascaded Aptamers-Governed Multistage Drug-Delivery System Based on Biodegradable Envelope-Type Nanovehicle for Targeted Therapy of HER2-Overexpressing Breast Cancer. ACS APPLIED MATERIALS & INTERFACES 2018; 10:34050-34059. [PMID: 30207689 DOI: 10.1021/acsami.8b14009] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Tumor-specific therapeutic platforms with improved targeting efficacy and minimized side effect are crucial in cancer therapy. Capitalizing on the recognition capability and biocompatibility of aptamers, we herein designed a multistage targeted drug-delivery system using multiple biodegradable molecules-enveloped nanovehicle that can be employed to efficiently treat human epithelial growth factor receptor (HER2)-overexpressing breast cancer. In this nanovehicle, two aptamers respectively specific to HER2 and ATP were organized in a hierarchical manner. The outmost HER2 aptamer (HB5) governs the recognition to HER2 protein overexpressed in SK-BR-3 cell lines, while the ATP aptamer incorporated with anticancer drug (-)-epigallocatechin gallate (EGCG) and protamine sulfate in the inner core functions as a switch of drug release in response to abundant intracellular ATP. The targeting and drug locker aptamers were cascaded for active targeting effect and stimuli responsiveness, guaranteeing the site-specific drug transportation and endogenous species-triggered drug release inside the tumor cells. Moreover, nanostructured lipid carriers (NLCs) were constructed to wrap and stabilize the loosely bounded ternary complex, minimizing premature drug leakage potentially encountered by the biomolecule assembled nanocarriers. This multiple biomolecules-enveloped nanovehicle demonstrated improved inhibitory actions on tumor growth and minimum side effect to normal organs and tissues both in vitro and in vivo. The presented nanovehicle built from recognition and therapeutic components in a nontoxic framework offered a promising drug-delivery platform with transport precision and biological safety.
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Affiliation(s)
- Tingxizi Liang
- State Key Laboratory of Analytical Chemistry and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry & Chemical Engineering , Nanjing University , Nanjing 210023 , China
| | - Zhigang Yao
- State Key Laboratory of Analytical Chemistry and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry & Chemical Engineering , Nanjing University , Nanjing 210023 , China
| | - Jie Ding
- State Key Laboratory of Analytical Chemistry and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry & Chemical Engineering , Nanjing University , Nanjing 210023 , China
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, China-America Cancer Research Institute , Guangdong Medical University , Dongguan 523808 , China
| | - Qianhao Min
- State Key Laboratory of Analytical Chemistry and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry & Chemical Engineering , Nanjing University , Nanjing 210023 , China
| | - Liping Jiang
- State Key Laboratory of Analytical Chemistry and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry & Chemical Engineering , Nanjing University , Nanjing 210023 , China
| | - Jun-Jie Zhu
- State Key Laboratory of Analytical Chemistry and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry & Chemical Engineering , Nanjing University , Nanjing 210023 , China
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41
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Co-transfection of star-shaped PDMAEMAs enhance transfection efficiency of protamine/pDNA complexes in the presence of serum. Eur Polym J 2018. [DOI: 10.1016/j.eurpolymj.2018.04.022] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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42
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Chen B, Yu L, Li Z, Wu C. Design of Free Triblock Polylysine-b-Polyleucine-b-Polylysine Chains for Gene Delivery. Biomacromolecules 2018; 19:1347-1357. [DOI: 10.1021/acs.biomac.8b00287] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Affiliation(s)
- Baizhu Chen
- Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
| | - Lei Yu
- Beijing National Laboratory for Molecular Sciences, Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
| | - Zhibo Li
- Beijing National Laboratory for Molecular Sciences, Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
| | - Chi Wu
- Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
- The Hefei National Laboratory of Physical Science at Microscale and Department of Chemical Physics, The University of Science and Technology of China, Hefei, Anhui 230026, China
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43
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Wang Y, Rajala A, Rajala RVS. Nanoparticles as Delivery Vehicles for the Treatment of Retinal Degenerative Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1074:117-123. [PMID: 29721935 DOI: 10.1007/978-3-319-75402-4_15] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Over the last few years, huge progress has been made in the understanding of molecular mechanisms underlying the pathogenesis of retinal degenerative diseases. Such knowledge has led to the development of gene therapy approaches to treat these devastating disorders. Non-viral gene delivery has been recognized as a prospective treatment for retinal degenerative diseases. In this review, we will summarize the constituent characteristics and recent applications of three representative nanoparticles (NPs) in ocular therapy.
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Affiliation(s)
- Yuhong Wang
- Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.,Dean McGee Eye Institute, Oklahoma City, OK, USA
| | - Ammaji Rajala
- Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.,Dean McGee Eye Institute, Oklahoma City, OK, USA
| | - Raju V S Rajala
- Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. .,Dean McGee Eye Institute, Oklahoma City, OK, USA. .,Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. .,Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
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44
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Campani V, Giarra S, De Rosa G. Lipid-based core-shell nanoparticles: Evolution and potentialities in drug delivery. OPENNANO 2018. [DOI: 10.1016/j.onano.2017.12.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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45
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Huang JL, Chen HZ, Gao XL. Lipid-coated calcium phosphate nanoparticle and beyond: a versatile platform for drug delivery. J Drug Target 2017; 26:398-406. [PMID: 29258343 DOI: 10.1080/1061186x.2017.1419360] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
In recent years, lipid-coated calcium-phosphate (LCP) nanoparticle has been developed as a versatile platform for delivery of various therapeutics including gene, protein/peptide, chemotherapeutics and theranostic agents. The high endosomal escape, coupled with the ability to efficiently encapsulate phosphorylated drugs or prodrugs, make LCP become attractive vehicle for drug delivery. Additionally, the principle behind LCP formulation has also allowed rational design of LCP-derived nanoparticles (NPs) with other solid core or lipid membrane to overcome the various drug delivery barriers. Here, we briefly review the history of the development of LCP NPs, highlight the optimisations and modulations in the development process, and summarise the major applications of LCP NPs and LCP-derived NPs in drug delivery.
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Affiliation(s)
- Jia-Lin Huang
- a Department of Pharmacology and Chemical Biology, Faculty of Basic Medicine , Shanghai Jiao Tong University School of Medicine , Shanghai , PR China.,b Department of Neurological Surgery , Renji Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , PR China
| | - Hong-Zhuan Chen
- a Department of Pharmacology and Chemical Biology, Faculty of Basic Medicine , Shanghai Jiao Tong University School of Medicine , Shanghai , PR China
| | - Xiao-Ling Gao
- a Department of Pharmacology and Chemical Biology, Faculty of Basic Medicine , Shanghai Jiao Tong University School of Medicine , Shanghai , PR China
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46
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Firouzmand H, Sahranavard M, Badiee A, Khamesipour A, Alavizadeh SH, Samiei A, Soroush D, Tavassoti Kheiri M, Mahboudi F, Jaafari MR. The role of LPD-nanoparticles containing recombinant major surface glycoprotein of Leishmania (rgp63) in protection against leishmaniasis in murine model. Immunopharmacol Immunotoxicol 2017; 40:72-82. [PMID: 29210292 DOI: 10.1080/08923973.2017.1407941] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
CONTEXT Leishmaniasis is a major public health problem. Despite numerous attempts, yet there is no effective vaccine against human leishmaniasis, mainly due to a lack of an effective vaccine delivery system as well as adjuvant. OBJECTIVE(S) The aim of this study was to evaluate the ability of recombinant glycoprotein 63 (rgp63) as a model of Leishmania antigen, entrapped in liposome-polycation-DNA (LPD) complexes nanoparticles in inducing cell mediated immune (CMI) response and protecting against L. major in BALB/c mice. MATERIALS AND METHODS To this end, the abundant leishmania promastigote cell surface glycoprotein, gp63, was entrapped in nano-sized LPD (CpG) particles, (LPD (CpG)-rgp63), and BALB/c mice were immunized three times with either (LPD (CpG)-rgp63) or rgp63-CpG DNA or LPD (CpG) or free rgp63 and dextrose 5%. Various parameters including footpad thickness, splenic load of L. major parasites, rgp63-binding IgGs and also cytokine levels of rgp63-reactive T lymphocytes were then compared among different vaccinated animals. RESULTS The lowest number of parasites in spleen, the higher levels of IgG2a after challenge infection, the minimal footpad swelling and high level of IFN-γ secretion, all indicated that adjuvants and antigen-delivery systems are essential in modifying immune responses; as mice received LPD (CpG)-rgp63 induced immune response stronger than the other groups. CONCLUSIONS This study demonstrates that LPD nanoparticle is a promising and adaptable delivery system which could be modified towards specific vaccine targets to induce a more potent immune response in combination with rgp63.
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Affiliation(s)
- Hengameh Firouzmand
- a Nanotechnology Research Center, Mashhad University of Medical Sciences , Mashhad , Iran
| | - Mehrnosh Sahranavard
- a Nanotechnology Research Center, Mashhad University of Medical Sciences , Mashhad , Iran.,b Department of Pharmaceutical Nanotechnology, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran
| | - Ali Badiee
- b Department of Pharmaceutical Nanotechnology, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.,c Biotechnology Research Center, Mashhad University of Medical Sciences , Mashhad , Iran
| | - Ali Khamesipour
- d Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences , Bandar Abbas , Iran
| | - Seyedeh Hoda Alavizadeh
- b Department of Pharmaceutical Nanotechnology, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.,c Biotechnology Research Center, Mashhad University of Medical Sciences , Mashhad , Iran
| | - Afshin Samiei
- e Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences , Tehran , Iran
| | - Dina Soroush
- a Nanotechnology Research Center, Mashhad University of Medical Sciences , Mashhad , Iran
| | | | - Fereidoun Mahboudi
- f Biotechnology Research Center, Pasteur Institute of Iran , Tehran , Iran
| | - Mahmoud Reza Jaafari
- a Nanotechnology Research Center, Mashhad University of Medical Sciences , Mashhad , Iran.,b Department of Pharmaceutical Nanotechnology, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.,c Biotechnology Research Center, Mashhad University of Medical Sciences , Mashhad , Iran
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47
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Nematollahi MH, Torkzadeh-Mahanai M, Pardakhty A, Ebrahimi Meimand HA, Asadikaram G. Ternary complex of plasmid DNA with NLS-Mu-Mu protein and cationic niosome for biocompatible and efficient gene delivery: a comparative study with protamine and lipofectamine. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2017; 46:1781-1791. [PMID: 29081256 DOI: 10.1080/21691401.2017.1392316] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Non-viral gene delivery methods are considered due to safety and simplicity in human gene therapy. Since the use of cationic peptide and niosome represent a promising approach for gene delivery purposes we used recombinant fusion protein and cationic niosome as a gene carrier. A multi-domain fusion protein including nuclear localization motif (NLS) and two DNA-binding (Mu) domains, namely NLS-Mu-Mu (NMM) has been designed, cloned and expressed in E. coli DE3 strain. Afterward, the interested protein was purified by affinity chromatography. Binary vectors based on protein/DNA and ternary vectors based on protein/DNA/niosome were prepared. Protamine was used as a control. DNA condensing properties of NMM and protamine were evaluated by various experiments. Furthermore, we examined cytotoxicity, hemolysis and transfection potential of the binary and ternary complexes in HEK293T and MCF-7 cell lines. Protamine and Lipofectamine™2000 were used as positive controls, correspondingly. The recombinant NMM was expressed and purified successfully and DNA was condensed efficiently at charge ratios that were not harmful to cells. Peptidoplexes showed transfection efficiency (TE) but ternary complexes had higher TE. Additionally, NMM ternary complex was more efficient compared to protamine ternary vectors. Our results showed that niosomal ternary vector of NMM is a promising non-viral gene carrier to achieve an effective and safe carrier system for gene therapy.
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Affiliation(s)
- Mohammad Hadi Nematollahi
- a Neurology Research Center , Kerman University of Medical Sciences , Kerman , Iran.,b Department of Biochemistry, School of Medicine , Kerman University of Medical Sciences , Kerman , Iran
| | - Masoud Torkzadeh-Mahanai
- c Biotechnology Department, Institute of Science and High Technology and Environmental Sciences , Graduate University of Advanced Technology , Kerman , Iran
| | - Abbas Pardakhty
- d Pharmaceutics Research Center, Institute of Neuropharmacology , Kerman University of Medical Science , Kerman , Iran
| | | | - Gholamreza Asadikaram
- b Department of Biochemistry, School of Medicine , Kerman University of Medical Sciences , Kerman , Iran.,e Neuroscience Research Center, Institute of Neuropharmacology , Kerman University of Medical Sciences , Kerman , Iran
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48
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Meng Z, Yang J, Liu Q, de Vries JW, Gruszka A, Rodríguez-Pulido A, Crielaard BJ, Kros A, Herrmann A. Efficient Fusion of Liposomes by Nucleobase Quadruple-Anchored DNA. Chemistry 2017; 23:9391-9396. [DOI: 10.1002/chem.201701379] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Indexed: 12/29/2022]
Affiliation(s)
- Zhuojun Meng
- Zernike Institute for Advanced Materials; University of Groningen; Nijenborgh 4 9747 AG Groningen The Netherlands
| | - Jian Yang
- Supramolecular & Biomaterials Chemistry, Leiden Institute of Chemistry; Leiden University, P.O. Box 9502; 2300 RA Leiden The Netherlands
| | - Qing Liu
- Zernike Institute for Advanced Materials; University of Groningen; Nijenborgh 4 9747 AG Groningen The Netherlands
| | - Jan Willem de Vries
- Zernike Institute for Advanced Materials; University of Groningen; Nijenborgh 4 9747 AG Groningen The Netherlands
| | - Agnieszka Gruszka
- Zernike Institute for Advanced Materials; University of Groningen; Nijenborgh 4 9747 AG Groningen The Netherlands
| | - Alberto Rodríguez-Pulido
- Zernike Institute for Advanced Materials; University of Groningen; Nijenborgh 4 9747 AG Groningen The Netherlands
| | - Bart J. Crielaard
- Zernike Institute for Advanced Materials; University of Groningen; Nijenborgh 4 9747 AG Groningen The Netherlands
- Institute for Biomedical Engineering and Materials Science; University Medical Center Groningen; Antonius Deusinglaan 1 9713AV Groningen The Netherlands
| | - Alexander Kros
- Supramolecular & Biomaterials Chemistry, Leiden Institute of Chemistry; Leiden University, P.O. Box 9502; 2300 RA Leiden The Netherlands
| | - Andreas Herrmann
- Zernike Institute for Advanced Materials; University of Groningen; Nijenborgh 4 9747 AG Groningen The Netherlands
- Institute for Biomedical Engineering and Materials Science; University Medical Center Groningen; Antonius Deusinglaan 1 9713AV Groningen The Netherlands
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49
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The offset effect of a hyaluronic acid coating to cationic carriers containing siRNA: Alleviated cytotoxicity and retained gene silencing in vitro. J Drug Deliv Sci Technol 2017. [DOI: 10.1016/j.jddst.2017.03.024] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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50
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Rabbani PS, Zhou A, Borab ZM, Frezzo JA, Srivastava N, More HT, Rifkin WJ, David JA, Berens SJ, Chen R, Hameedi S, Junejo MH, Kim C, Sartor RA, Liu CF, Saadeh PB, Montclare JK, Ceradini DJ. Novel lipoproteoplex delivers Keap1 siRNA based gene therapy to accelerate diabetic wound healing. Biomaterials 2017; 132:1-15. [PMID: 28391065 DOI: 10.1016/j.biomaterials.2017.04.001] [Citation(s) in RCA: 102] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Revised: 03/29/2017] [Accepted: 04/03/2017] [Indexed: 12/20/2022]
Abstract
Therapeutics utilizing siRNA are currently limited by the availability of safe and effective delivery systems. Cutaneous diseases, specifically ones with significant genetic components are ideal candidates for topical siRNA based therapy but the anatomical structure of skin presents a considerable hurdle. Here, we optimized a novel liposome and protein hybrid nanoparticle delivery system for the topical treatment of diabetic wounds with severe oxidative stress. We utilized a cationic lipid nanoparticle (CLN) composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the edge activator sodium cholate (NaChol), in a 6:1 ratio of DOTAP:NaChol (DNC). Addition of a cationic engineered supercharged coiled-coil protein (CSP) in a 10:1:1 ratio of DNC:CSP:siRNA produced a stable lipoproteoplex (LPP) nanoparticle, with optimal siRNA complexation, minimal cytotoxicity, and increased transfection efficacy. In a humanized murine diabetic wound healing model, our optimized LPP formulation successfully delivered siRNA targeted against Keap1, key repressor of Nrf2 which is a central regulator of redox mechanisms. Application of LPP complexing siKeap1 restored Nrf2 antioxidant function, accelerated diabetic tissue regeneration, and augmented reduction-oxidation homeostasis in the wound environment. Our topical LPP delivery system can readily be translated into clinical use for the treatment of diabetic wounds and can be extended to other cutaneous diseases with genetic components.
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Affiliation(s)
- Piul S Rabbani
- New York University School of Medicine, Hansjörg Wyss Department of Plastic and Reconstructive Surgery, 430 East 29th Street, New York, NY, 10016, United States
| | - Anna Zhou
- New York University School of Medicine, Hansjörg Wyss Department of Plastic and Reconstructive Surgery, 430 East 29th Street, New York, NY, 10016, United States
| | - Zachary M Borab
- New York University School of Medicine, Hansjörg Wyss Department of Plastic and Reconstructive Surgery, 430 East 29th Street, New York, NY, 10016, United States
| | - Joseph A Frezzo
- New York University Tandon School of Engineering, Chemical and Biomolecular Engineering Department, 6 Metrotech Center, Brooklyn, NY 11201, United States
| | - Nikita Srivastava
- New York University Tandon School of Engineering, Chemical and Biomolecular Engineering Department, 6 Metrotech Center, Brooklyn, NY 11201, United States
| | - Haresh T More
- New York University Tandon School of Engineering, Chemical and Biomolecular Engineering Department, 6 Metrotech Center, Brooklyn, NY 11201, United States
| | - William J Rifkin
- New York University School of Medicine, Hansjörg Wyss Department of Plastic and Reconstructive Surgery, 430 East 29th Street, New York, NY, 10016, United States
| | - Joshua A David
- New York University School of Medicine, Hansjörg Wyss Department of Plastic and Reconstructive Surgery, 430 East 29th Street, New York, NY, 10016, United States
| | - Samuel J Berens
- New York University Tandon School of Engineering, Chemical and Biomolecular Engineering Department, 6 Metrotech Center, Brooklyn, NY 11201, United States
| | - Raymond Chen
- New York University Tandon School of Engineering, Chemical and Biomolecular Engineering Department, 6 Metrotech Center, Brooklyn, NY 11201, United States
| | - Sophia Hameedi
- New York University School of Medicine, Hansjörg Wyss Department of Plastic and Reconstructive Surgery, 430 East 29th Street, New York, NY, 10016, United States
| | - Muhammad H Junejo
- New York University School of Medicine, Hansjörg Wyss Department of Plastic and Reconstructive Surgery, 430 East 29th Street, New York, NY, 10016, United States
| | - Camille Kim
- New York University School of Medicine, Hansjörg Wyss Department of Plastic and Reconstructive Surgery, 430 East 29th Street, New York, NY, 10016, United States
| | - Rita A Sartor
- New York University School of Medicine, Hansjörg Wyss Department of Plastic and Reconstructive Surgery, 430 East 29th Street, New York, NY, 10016, United States
| | - Che F Liu
- New York University Tandon School of Engineering, Chemical and Biomolecular Engineering Department, 6 Metrotech Center, Brooklyn, NY 11201, United States
| | - Pierre B Saadeh
- New York University School of Medicine, Hansjörg Wyss Department of Plastic and Reconstructive Surgery, 430 East 29th Street, New York, NY, 10016, United States
| | - Jin K Montclare
- New York University Tandon School of Engineering, Chemical and Biomolecular Engineering Department, 6 Metrotech Center, Brooklyn, NY 11201, United States; New York University, Chemistry Department, 100 Washington Square East, New York, NY 10003, United States
| | - Daniel J Ceradini
- New York University School of Medicine, Hansjörg Wyss Department of Plastic and Reconstructive Surgery, 430 East 29th Street, New York, NY, 10016, United States.
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