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Qian H, Pan J, Li X, Du J, Gu L, Miao Y, Gao H, Zhang J, Li Y. Anion exchange regulated charge separation engineering in bismuth nanoflowers for sonocatalytic radio-immunotherapy. J Colloid Interface Sci 2025; 687:801-816. [PMID: 39986009 DOI: 10.1016/j.jcis.2025.02.113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 02/15/2025] [Accepted: 02/16/2025] [Indexed: 02/24/2025]
Abstract
Ultrasound and X-ray are considered potential options in cancer therapy due to their superior tissue penetration capabilities. Developing effective radiosensitizers is crucial for advancing cancer treatment as they enhance the effectiveness of radiation and sonodynamic therapies while minimizing their side effects. This study aimed to design a degradable bismuth-based heterojunction BiF3-Bi2O3-x:Sx-PEG (BFOSP) radiosensitizer using anion-exchange-regulated charge separation engineering. The heterojunction regulated the bandgap, improved charge carrier mobility, and enhanced reactive oxygen species generation efficiency by introducing O and S anions, enhancing the synergistic effects of sonodynamic therapy and radiotherapy. Sonodynamic therapy reduces the required radiotherapy dose, thus improving the synergistic therapeutic efficacy while enhancing treatment safety. The degradation and oxidative stress effects of BFOSP further disrupted redox balance in the tumor microenvironment while inducing tumor cell apoptosis, ferroptosis, and immunogenic cell death, activating systemic immune responses. This study introduces a reasonable design strategy for degradable radiosensitizers, offering a promising approach to improving synergy and advancing comprehensive cancer therapy.
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Affiliation(s)
- Huihui Qian
- Institute of Bismuth Science, School of Materials and Chemistry, Shanghai Collaborative Innovation Center of Energy Therapy for Tumors, University of Shanghai for Science and Technology, Shanghai 200093, China; Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Junjie Pan
- Institute of Bismuth Science, School of Materials and Chemistry, Shanghai Collaborative Innovation Center of Energy Therapy for Tumors, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Xueyu Li
- Institute of Bismuth Science, School of Materials and Chemistry, Shanghai Collaborative Innovation Center of Energy Therapy for Tumors, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Jun Du
- Institute of Bismuth Science, School of Materials and Chemistry, Shanghai Collaborative Innovation Center of Energy Therapy for Tumors, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Liping Gu
- Institute of Bismuth Science, School of Materials and Chemistry, Shanghai Collaborative Innovation Center of Energy Therapy for Tumors, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Yuqing Miao
- Institute of Bismuth Science, School of Materials and Chemistry, Shanghai Collaborative Innovation Center of Energy Therapy for Tumors, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Hongbo Gao
- Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai 200040, China.
| | - Jiawen Zhang
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China.
| | - Yuhao Li
- Institute of Bismuth Science, School of Materials and Chemistry, Shanghai Collaborative Innovation Center of Energy Therapy for Tumors, University of Shanghai for Science and Technology, Shanghai 200093, China.
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Jiao W, Zhou H, Zhang J, Yuan Y, Wei J, Gong X, Sun Y, Sang L, Yu M. Mesoporous silica nanoparticles as sensitizers: A novel approach to enhancing shear wave elastography in liver stiffness measurement. BIOMATERIALS ADVANCES 2025; 169:214171. [PMID: 39764903 DOI: 10.1016/j.bioadv.2024.214171] [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: 08/12/2024] [Revised: 12/12/2024] [Accepted: 12/27/2024] [Indexed: 02/04/2025]
Abstract
PURPOSE The objective of this study is to elucidate the sensitizing effect of mesoporous silica nanoparticles (MSNs) on shear wave elastography (SWE) and to investigate the potential application of MSNs as a sensitizer to enhance the sensitivity of SWE in the diagnosis of metabolic-associated steatohepatitis (MASH). MATERIALS AND METHODS The in vitro gelatin models with varying ratios were assessed using SWE to identify the gelatin ratio that most closely approximates with human liver stiffness. Following the characterization of the dispersion properties of MSNs, in vitro models incorporating MSNs of different particle sizes were developed. The variations in shear wave velocity (SWV) within these models were measured and subjected to statistical analysis using SWE. The biocompatibility of the MSNs was evaluated, and the MSN solution was subsequently administered into a MASH animal model. The sensitizing effect of SWE on rat liver was then analyzed statistically. RESULTS The in vitro model demonstrated that MSNs with smaller particle sizes (100 nm and 200 nm) facilitated the propagation of SWV, thereby enhancing the sensitivity of SWE (P < 0.05). Additionally, the cell viability and hemolysis ratio of 100 nm MSNs were superior to those of 200 nm MSNs (P < 0.05). In vivo animal model experiments indicated that 100 nm fluorescence-modified MSNs could penetrate the MASH liver and elevate the liver stiffness value as measured by SWE. CONCLUSION MSNs have the potential to enhance the sensitivity of SWE in the diagnosis of MASH. This approach offers novel insights for improving the efficacy of SWE in clinical diagnostic and therapeutic applications.
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Affiliation(s)
- Weijie Jiao
- Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, No.127 Changle West Rd, 710032 Xi'an, Shaanxi, China
| | - Huihui Zhou
- Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, No.127 Changle West Rd, 710032 Xi'an, Shaanxi, China
| | - Jun Zhang
- Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, No.127 Changle West Rd, 710032 Xi'an, Shaanxi, China
| | - Yuan Yuan
- Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, No.169 Changle West Rd, 710032 Xi'an, China
| | - Junci Wei
- Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, No.127 Changle West Rd, 710032 Xi'an, Shaanxi, China
| | - Xue Gong
- Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, No.127 Changle West Rd, 710032 Xi'an, Shaanxi, China
| | - Yuanyuan Sun
- Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, No.127 Changle West Rd, 710032 Xi'an, Shaanxi, China
| | - Lin Sang
- Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, No.127 Changle West Rd, 710032 Xi'an, Shaanxi, China
| | - Ming Yu
- Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, No.127 Changle West Rd, 710032 Xi'an, Shaanxi, China.
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Zhang K, Wang T, Huang X, Wu P, Shen L, Yang Y, Wan W, Sun S, Zhang Z. Ultrasound-mediated nanomaterials for the treatment of inflammatory diseases. ULTRASONICS SONOCHEMISTRY 2025; 114:107270. [PMID: 39961217 DOI: 10.1016/j.ultsonch.2025.107270] [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: 12/12/2024] [Revised: 02/01/2025] [Accepted: 02/11/2025] [Indexed: 03/03/2025]
Abstract
Sterile and infection-associated inflammatory diseases are becoming increasingly prevalent worldwide. Conventional drug therapies often entail significant drawbacks, such as the risk of drug overdose, the development of drug resistance in pathogens, and systemic adverse reactions, all of which can undermine the effectiveness of treatments for these conditions. Nanomaterials (NMs) have emerged as a promising tool in the treatment of inflammatory diseases due to their precise targeting capabilities, tunable characteristics, and responsiveness to external stimuli. Ultrasound (US), a non-invasive and effective treatment method, has been explored in combination with NMs to achieve enhanced therapeutic outcomes. This review provides a comprehensive overview of the recent advances in the use of US-mediated NMs for treating inflammatory diseases. A comprehensive introduction to the application and classification of US was first presented, emphasizing the advantages of US-mediated NMs and the mechanisms through which US and NMs interact to enhance anti-inflammatory therapy. Subsequently, specific applications of US-mediated NMs in sterile and infection-associated inflammation were summarized. Finally, the challenges and prospects of US-mediated NMs in clinical translation were discussed, along with an outline of future research directions. This review aims to provide insights to guide the development and improvement of US-mediated NMs for more effective therapeutic interventions in inflammatory diseases.
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Affiliation(s)
- Kai Zhang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, PR China; Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, PR China
| | - Tingting Wang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, PR China
| | - Xingyong Huang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, PR China
| | - Peng Wu
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, PR China
| | - Lufan Shen
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, PR China
| | - Yuanyuan Yang
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, PR China
| | - Wenyu Wan
- Key Laboratory of Immunodermatology, Ministry of Education, Department of Dermatology, The First Hospital of China Medical University, PR China; Key Laboratory of Immunodermatology, National Health Commission of the People's Republic of China, The First Hospital of China Medical University, PR China; National and Local Joint Engineering Research Center of Immunodermatological Theranostics, The First Hospital of China Medical University, PR China.
| | - Siyu Sun
- Department of Gastroenterology, Endoscopic Center, Shengjing Hospital of China Medical University, PR China; Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic Techniques, Shengjing Hospital of China Medical University, PR China.
| | - Zhan Zhang
- Department of Oncology, Shengjing Hospital of China Medical University, PR China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, PR China.
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Li L, Tian H, Wu L, Chen N, Zhang Q, Chen L, Zhu K, Lin L, Chen X, He L, Liu M, Zhao W, Su Y, Yan J, Zhao X, Zhou X, Zhou Z, Zeng W. Artificial biomarker-based feedback-regulated personalized and precise thrombolysis with lower hemorrhagic risk. SCIENCE ADVANCES 2025; 11:eadr0377. [PMID: 39823346 PMCID: PMC11740970 DOI: 10.1126/sciadv.adr0377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 12/16/2024] [Indexed: 01/19/2025]
Abstract
The body weight-based thrombolytic medication strategy in clinical trials shows critical defects in recanalization rate and post-thrombolysis hemorrhage. Methods for perceiving thrombi heterogeneity of thrombolysis resistance is urgently needed for precise thrombolysis. Here, we revealed the relationship between the thrombin heterogeneity and the thrombolysis resistance in thrombi and created an artificial biomarker-based nano-patrol system with robotic functional logic to perceive and report the thrombolysis resistance of thrombi. The nano-patrols are contrallable and are able to accomplish thrombolysis resistance-matched personalized and precise therapy according to the feedback signal from artificial biomarkers. This nano-patrol system depicted more enhanced thrombolytic efficiency (elevated by 25%) than alteplase for mini pig model and clinical thrombi and achieved recanalization in thrombotic model where alteplase encountered failure. Moreover, the nano-patrol remarkably reduced the infarct volume and the hemorrhagic transformation risk (0.12-fold of alteplase) of cerebral thrombosis. Therefore, we developed a unique tool for diagnosing thrombolysis resistance and achieving personalized and precise thrombolysis.
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Affiliation(s)
- Lang Li
- Department of Cell Biology, Third Military Medical University, Chongqing, China
- Jinfeng Laboratory, Chongqing, China
- State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, China
| | - Hao Tian
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Liulin Wu
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Na Chen
- School of Medicine, Chongqing University, Chongqing, China
| | - Qiao Zhang
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Lin Chen
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Kai Zhu
- Advanced Photonics Center, School of Electronic Science and Engineering, Southeast University, Nanjing, China
| | - Lin Lin
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Xi Chen
- Department of Neurology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Lang He
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Min Liu
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Wenyan Zhao
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Yang Su
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Juan Yan
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Xingli Zhao
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Xin Zhou
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Zhenhua Zhou
- Department of Neurology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Wen Zeng
- Department of Cell Biology, Third Military Medical University, Chongqing, China
- Jinfeng Laboratory, Chongqing, China
- State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, China
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Zhang W, Sun M, Xu L, Chen S, Rong X, Wang J, Liu J, Liu B, Xu J, Luo Y, Du Q, Wang Y, Liu Y, Wang Z, Ran H, Guo D. Low‐Intensity Focused Ultrasound‐Responsive Nanobubbles Enhance Thrombus Targeting and Penetration for Highly Effective Thrombolytic Therapy. SMALL STRUCTURES 2024. [DOI: 10.1002/sstr.202400541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Owing to the short half‐life, restricted targeting capability, and high bleeding risk associated with thrombolytic drugs, safe and effective thrombolytic therapy remains challenging. Based on the natural targeting and immune escape functions of platelets during thrombosis, spatiotemporally controlled nanobubbles (PAF@M) are developed to specifically target thrombus sites. These nanobubbles are designed by loading an air core of perfluoropentane (PFP) and l‐arginine within a poly(lactic‐co‐glycolic acid) shell and coating it with a platelet membrane. Under stimulation with low‐intensity focused ultrasound (LIFU), physical shear stress promotes deep penetration of the nanobubbles into the thrombus. Moreover, the liquid–gas phase transition of PFP and the release of nitric oxide synergistically enhance ultrasonic cavitation to disrupt the thrombus structure. In terms of mechanism, these gas molecules induce acoustic pore action to disrupt the fibrin network structure, loosening the interior of the thrombus, and act specifically on the surfaces of red blood cells and activated platelets, launching a comprehensive attack on the thrombus. It is believed that PAF@M nanobubbles will delay the progression of thrombosis and achieve safe and highly effective thrombolytic therapy. This simple LIFU response principle has the potential to be a safer and more effective alternative to current pharmaceutical approaches.
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Affiliation(s)
- Wenli Zhang
- Department of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
| | - Maoyuan Sun
- Department of Neurosurgery Huashan Hospital Fudan University Shanghai 200000 China
| | - Lian Xu
- Department of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
| | - Sijin Chen
- Department of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
| | - Xiyue Rong
- Department of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
| | - Junrui Wang
- Department of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
| | - Jia Liu
- Department of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
| | - Bo Liu
- Department of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
| | - Jie Xu
- Department of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
| | - Ying Luo
- Department of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
| | - Qianying Du
- Department of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
| | - Yi Wang
- Department of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
| | - Yun Liu
- Department of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
| | - Zhigang Wang
- Department of Ultrasound & Chongqing Key Laboratory of Ultrasound Molecular Imaging The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
| | - Haitao Ran
- Department of Ultrasound & Chongqing Key Laboratory of Ultrasound Molecular Imaging The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
| | - Dajing Guo
- Department of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China
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Cao M, Yang S, Li J, Yang Y, Zhan L, Wang T, Hu T, Liang R, Li Z. Bifunctional Bismuth-Based Layered Double Hydroxide Sonosensitizer for Magnetic Resonance Imaging-Guided Sonodynamic Cancer Therapy. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2404475. [PMID: 39212201 DOI: 10.1002/smll.202404475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 08/13/2024] [Indexed: 09/04/2024]
Abstract
Novel inorganic sonosensitizers with excellent reactive oxygen species (ROS) generation activity and multifunctionality are appealing in sonodynamic therapy (SDT). Herein, amorphous bismuth (Bi)-doped CoFe-layered double hydroxide (a-CoBiFe-LDH) nanosheets are proposed via crystalline-to-amorphous phase transformation strategy as a new type of bifunctional sonosensitizer, which allows ultrasound (US) to trigger ROS generation for magnetic resonance imaging (MRI)-guided SDT. Importantly, a-CoBiFe-LDH nanosheets exhibit much higher ROS generation activity (≈6.9 times) than that of traditional TiO2 sonosensitizer under US irradiation, which can be attributed to the acid etching-induced narrow band gap, high electron (e-)/hole (h+) separation efficiency and inhibited e-/h+ recombination. In addition, the paramagnetic properties of Fe ion endow a-CoBiFe-LDH with excellent MRI contrast ability, making it a promising contrast agent for T2-weighted MRI. After modification with polyethylene glycol, a-CoBiFe-LDH nanosheets can function as a high-efficiency sonosensitizer to activate p53, MAPK, oxidative phosphorylation, and apoptosis-related signaling pathways, ultimately inducing cell apoptosis in vitro and tumor ablation in vivo under US irradiation, which shows great potential for clinical cancer treatment.
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Affiliation(s)
- Min Cao
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, P. R. China
| | - Shuqing Yang
- State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Jie Li
- College of Pharmacy, Wenzhou Medical University, Wenzhou, 325000, P. R. China
| | - Yu Yang
- State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Linsen Zhan
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, P. R. China
| | - Tao Wang
- State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Tingting Hu
- State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Ruizheng Liang
- State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
- Quzhou Institute for Innovation in Resource Chemical Engineering, Quzhou, 324000, P. R. China
| | - Zhangping Li
- The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, P. R. China
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Wang Z, Zhang M, Du X. Construction of Yolk@shell Nanocomposite Particles with Controlled Multisized Pore Structures by Monomicelle Confined Assembly. ACS NANO 2024; 18:27511-27523. [PMID: 39320116 DOI: 10.1021/acsnano.4c08285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2024]
Abstract
Hollow nanoparticles with tunable structures and spatial and chemical specificity are considered as promising carriers. However, it remains a formidable challenge to endow hollow nanomaterials with precisely controlled multisized macro/mesoporous structures up to now. This paper demonstrates a "polydopamine (PDA) expansion-shrinkage" strategy combined with a monomicelle interfacial confined assembly method to achieve the highly controllable preparation of a series of yolk@shell PDA@SiO2 composite nanoparticles with structural asymmetry and a tunable multisized pore in the shell. The strategy allows systematic manipulation of the average pore size of large slit pores in the range of 15.4-86.5 nm by adjusting the reaction temperature. Benefiting from advantages such as an asymmetric structure and multilevel porosity, they exhibit excellent performance in the applications of on-demand loading of dual-sized cargoes, dual-propelled nanomotors, and particle size-selected encapsulation and separation. These findings provide inspiration for the construction of asymmetric yolk@shell structures with tunable multisized pores for a wide range of biological and chemical applications.
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Affiliation(s)
- Zhiming Wang
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry & Biological Engineering, University of Science & Technology Beijing, Beijing 100083, China
| | - Meiqin Zhang
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry & Biological Engineering, University of Science & Technology Beijing, Beijing 100083, China
| | - Xin Du
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry & Biological Engineering, University of Science & Technology Beijing, Beijing 100083, China
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Lin L, Ba Z, Tian H, Qin H, Chen X, Zhou X, Zhao S, Li L, Xue F, Li H, He L, Li X, Du J, Zhou Z, Zeng W. Ultrasound-responsive theranostic platform for the timely monitoring and efficient thrombolysis in thrombi of tPA resistance. Nat Commun 2024; 15:6610. [PMID: 39098904 PMCID: PMC11298549 DOI: 10.1038/s41467-024-50741-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 07/08/2024] [Indexed: 08/06/2024] Open
Abstract
There is no effective and noninvasive solution for thrombolysis because the mechanism by which certain thrombi become tissue plasminogen activator (tPA)-resistant remains obscure. Endovascular thrombectomy is the last option for these tPA-resistant thrombi, thus a new noninvasive strategy is urgently needed. Through an examination of thrombi retrieved from stroke patients, we found that neutrophil extracellular traps (NETs), ε-(γ-glutamyl) lysine isopeptide bonds and fibrin scaffolds jointly comprise the key chain in tPA resistance. A theranostic platform is designed to combine sonodynamic and mechanical thrombolysis under the guidance of ultrasonic imaging. Breakdown of the key chain leads to a recanalization rate of more than 90% in male rat tPA-resistant occlusion model. Vascular reconstruction is observed one month after recanalization, during which there was no thrombosis recurrence. The system also demonstrates noninvasive theranostic capabilities in managing pigs' long thrombi (>8 mm) and in revascularizing thrombosis-susceptible tissue-engineered vascular grafts, indicating its potential for clinical application. Overall, this noninvasive theranostic platform provides a new strategy for treating tPA-resistant thrombi.
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Affiliation(s)
- Lin Lin
- Department of Cell Biology, Third Military Medical University, Chongqing, China
- School of Medicine, Chongqing University, Chongqing, China
- Chongqing Institute of Advanced Pathology, Jinfeng Laboratory, Chongqing, China
| | - Zhaojing Ba
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Hao Tian
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Haoxiang Qin
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Xi Chen
- Department of Neurology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Xin Zhou
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Shanlan Zhao
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Lang Li
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Fangchao Xue
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Hong Li
- Department of Anesthesiology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Lang He
- Department of Cell Biology, Third Military Medical University, Chongqing, China
- Chongqing Institute of Advanced Pathology, Jinfeng Laboratory, Chongqing, China
| | - Xiaochen Li
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Jiahui Du
- Department of Cell Biology, Third Military Medical University, Chongqing, China
| | - Zhenhua Zhou
- Department of Neurology, Southwest Hospital, Third Military Medical University, Chongqing, China.
| | - Wen Zeng
- Department of Cell Biology, Third Military Medical University, Chongqing, China.
- Chongqing Institute of Advanced Pathology, Jinfeng Laboratory, Chongqing, China.
- State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.
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Yang S, Hu T, Williams GR, Yang Y, Zhang S, Shen J, Chen M, Liang R, Lyu L. Boosting the sonodynamic performance of CoBiMn-layered double hydroxide nanoparticles via tumor microenvironment regulation for ultrasound imaging-guided sonodynamic therapy. J Nanobiotechnology 2024; 22:317. [PMID: 38849886 PMCID: PMC11161954 DOI: 10.1186/s12951-024-02591-5] [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: 03/12/2024] [Accepted: 05/28/2024] [Indexed: 06/09/2024] Open
Abstract
Sonodynamic therapy (SDT), a promising strategy for cancer treatment with the ability for deep tissue penetration, has received widespread attention in recent years. Sonosensitizers with intrinsic characteristics for tumor-specific curative effects, tumor microenvironment (TME) regulation and tumor diagnosis are in high demand. Herein, amorphous CoBiMn-layered double hydroxide (a-CoBiMn-LDH) nanoparticles are presented as multifunctional sonosensitizers to trigger reactive oxygen species (ROS) generation for ultrasound (US) imaging-guided SDT. Hydrothermal-synthesized CoBiMn-LDH nanoparticles are etched via a simple acid treatment to obtain a-CoBiMn-LDH nanoparticles with abundant defects. The a-CoBiMn-LDH nanoparticles give greater ROS generation upon US irradiation, reaching levels ~ 3.3 times and ~ 8.2 times those of the crystalline CoBiMn-LDH nanoparticles and commercial TiO2 sonosensitizer, respectively. This excellent US-triggered ROS generation performance can be attributed to the defect-induced narrow band gap and promoted electrons and holes (e-/h+) separation. More importantly, the presence of Mn4+ enables the a-CoBiMn-LDH nanoparticles to regulate the TME by decomposing H2O2 into O2 for hypoxia relief and US imaging, and consuming glutathione (GSH) for protection against ROS clearance. Biological mechanism analysis shows that a-CoBiMn-LDH nanoparticles modified with polyethylene glycol can serve as a multifunctional sonosensitizer to effectively kill cancer cells in vitro and eliminate tumors in vivo under US irradiation by activating p53, apoptosis, and oxidative phosphorylation-related signaling pathways.
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Affiliation(s)
- Shuqing Yang
- State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Tingting Hu
- Department Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, 999077, P. R. China
| | - Gareth R Williams
- UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK
| | - Yu Yang
- State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China
| | - Susu Zhang
- Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, P. R. China
| | - Jiayi Shen
- Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, P. R. China
| | - Minjiang Chen
- Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, P. R. China.
| | - Ruizheng Liang
- State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China.
- Quzhou Institute for Innovation in Resource Chemical Engineering, Quzhou, 324000, P. R. China.
| | - Lingchun Lyu
- Lishui Central Hospital and the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, P. R. China.
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Pan X, Huang W, Nie G, Wang C, Wang H. Ultrasound-Sensitive Intelligent Nanosystems: A Promising Strategy for the Treatment of Neurological Diseases. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2303180. [PMID: 37871967 DOI: 10.1002/adma.202303180] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 09/26/2023] [Indexed: 10/25/2023]
Abstract
Neurological diseases are a major global health challenge, affecting hundreds of millions of people worldwide. Ultrasound therapy plays an irreplaceable role in the treatment of neurological diseases due to its noninvasive, highly focused, and strong tissue penetration capabilities. However, the complexity of brain and nervous system and the safety risks associated with prolonged exposure to ultrasound therapy severely limit the applicability of ultrasound therapy. Ultrasound-sensitive intelligent nanosystems (USINs) are a novel therapeutic strategy for neurological diseases that bring greater spatiotemporal controllability and improve safety to overcome these challenges. This review provides a detailed overview of therapeutic strategies and clinical advances of ultrasound in neurological diseases, focusing on the potential of USINs-based ultrasound in the treatment of neurological diseases. Based on the physical and chemical effects induced by ultrasound, rational design of USINs is a prerequisite for improving the efficacy of ultrasound therapy. Recent developments of ultrasound-sensitive nanocarriers and nanoagents are systemically reviewed. Finally, the challenges and developing prospects of USINs are discussed in depth, with a view to providing useful insights and guidance for efficient ultrasound treatment of neurological diseases.
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Affiliation(s)
- Xueting Pan
- CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China
| | - Wenping Huang
- CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China
- School of Nanoscience and Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Guangjun Nie
- CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China
- School of Nanoscience and Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Changyong Wang
- Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing, 100850, China
| | - Hai Wang
- CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China
- School of Nanoscience and Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
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11
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Hu H, Xia L, Wang J, Huang X, Zhao Q, Song X, Hu L, Ren S, Lu C, Ren Y, Qian X, Feng W, Wang Z, Chen Y. Bionanoengineered 2D monoelemental selenene for piezothrombolysis. Biomaterials 2024; 305:122468. [PMID: 38219628 DOI: 10.1016/j.biomaterials.2024.122468] [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: 11/05/2023] [Revised: 01/04/2024] [Accepted: 01/04/2024] [Indexed: 01/16/2024]
Abstract
Thrombosis-related diseases represent the leading causes of disability or death worldwide. However, conventional thrombolytic therapies are subjected to narrow therapeutic window, short circulation half-life and bleeding. Herein, we rationally design and develop a safe and efficient nonpharmaceutical thrombolysis strategy based on a specific piezocatalytic effect arising from platelet membrane (PM)-conjugated two-dimensional (2D) piezoelectric selenene, Se-PM nanosheets (NSs). The 2D selenene is fabricated from nonlayered bulk selenium powder by a facile liquid-phase exfoliation method, and the PM conjugation confers selenene with the distinct thrombus-homing feature. Under ultrasonic activation, the piezoelectric characteristic of selenene triggers electrons and holes separation, resulting in generation of reactive oxygen species (ROS) by reacting with surrounding H2O and O2 in the thrombosis microenvironment for thrombolysis. Both systematic in vitro and in vivo assessments demonstrate that the biocompatible Se-PM NSs efficiently degrade erythrocytes, fibrin and artificial blood clots under ultrasound irradiation. Compared to the clinical thrombolytic drug urokinase plasminogen activator, the engineered Se-PM NSs possess excellent thrombolytic efficacy by single treatment in the tail thrombosis animal model without bleeding risk. The engineered Se-PM nanoplatform marks an exciting jumping-off point for research into the application of piezocatalysis in clinical treatment of thrombosis.
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Affiliation(s)
- Hui Hu
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210004, PR China; Institute of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, PR China; Medmaterial Research Center, Jiangsu University Affiliated People's Hospital, Zhenjiang, 212002, PR China
| | - Lili Xia
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, PR China
| | - Junfeng Wang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210004, PR China
| | - Xuefei Huang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210004, PR China
| | - Qianqian Zhao
- Institute of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, PR China
| | - Xinyu Song
- Institute of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, PR China
| | - Lei Hu
- Institute of Diagnostic and Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, PR China
| | - Shuai Ren
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210004, PR China
| | - Chao Lu
- Medmaterial Research Center, Jiangsu University Affiliated People's Hospital, Zhenjiang, 212002, PR China
| | - Yongzhen Ren
- Medmaterial Research Center, Jiangsu University Affiliated People's Hospital, Zhenjiang, 212002, PR China
| | - Xiaoqin Qian
- Medmaterial Research Center, Jiangsu University Affiliated People's Hospital, Zhenjiang, 212002, PR China; Department of Ultrasound Medicine, Northen Jiangsu People's Hospital, Yangzhou, Jiangsu, 225009 PR China.
| | - Wei Feng
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, PR China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute of Shanghai University, Wenzhou, Zhejiang, 325088, PR China.
| | - Zhongqiu Wang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210004, PR China.
| | - Yu Chen
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, PR China; Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute of Shanghai University, Wenzhou, Zhejiang, 325088, PR China.
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12
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Chen L, Zhang S, Duan Y, Song X, Chang M, Feng W, Chen Y. Silicon-containing nanomedicine and biomaterials: materials chemistry, multi-dimensional design, and biomedical application. Chem Soc Rev 2024; 53:1167-1315. [PMID: 38168612 DOI: 10.1039/d1cs01022k] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
The invention of silica-based bioactive glass in the late 1960s has sparked significant interest in exploring a wide range of silicon-containing biomaterials from the macroscale to the nanoscale. Over the past few decades, these biomaterials have been extensively explored for their potential in diverse biomedical applications, considering their remarkable bioactivity, excellent biocompatibility, facile surface functionalization, controllable synthesis, etc. However, to expedite the clinical translation and the unexpected utilization of silicon-composed nanomedicine and biomaterials, it is highly desirable to achieve a thorough comprehension of their characteristics and biological effects from an overall perspective. In this review, we provide a comprehensive discussion on the state-of-the-art progress of silicon-composed biomaterials, including their classification, characteristics, fabrication methods, and versatile biomedical applications. Additionally, we highlight the multi-dimensional design of both pure and hybrid silicon-composed nanomedicine and biomaterials and their intrinsic biological effects and interactions with biological systems. Their extensive biomedical applications span from drug delivery and bioimaging to therapeutic interventions and regenerative medicine, showcasing the significance of their rational design and fabrication to meet specific requirements and optimize their theranostic performance. Additionally, we offer insights into the future prospects and potential challenges regarding silicon-composed nanomedicine and biomaterials. By shedding light on these exciting research advances, we aspire to foster further progress in the biomedical field and drive the development of innovative silicon-composed nanomedicine and biomaterials with transformative applications in biomedicine.
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Affiliation(s)
- Liang Chen
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China.
| | - Shanshan Zhang
- Department of Ultrasound Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P. R. China
| | - Yanqiu Duan
- Laboratory Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, P. R. China.
| | - Xinran Song
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China.
| | - Meiqi Chang
- Laboratory Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, P. R. China.
| | - Wei Feng
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China.
| | - Yu Chen
- Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China.
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13
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Xu B, Li S, Shi R, Liu H. Multifunctional mesoporous silica nanoparticles for biomedical applications. Signal Transduct Target Ther 2023; 8:435. [PMID: 37996406 PMCID: PMC10667354 DOI: 10.1038/s41392-023-01654-7] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 09/07/2023] [Accepted: 09/10/2023] [Indexed: 11/25/2023] Open
Abstract
Mesoporous silica nanoparticles (MSNs) are recognized as a prime example of nanotechnology applied in the biomedical field, due to their easily tunable structure and composition, diverse surface functionalization properties, and excellent biocompatibility. Over the past two decades, researchers have developed a wide variety of MSNs-based nanoplatforms through careful design and controlled preparation techniques, demonstrating their adaptability to various biomedical application scenarios. With the continuous breakthroughs of MSNs in the fields of biosensing, disease diagnosis and treatment, tissue engineering, etc., MSNs are gradually moving from basic research to clinical trials. In this review, we provide a detailed summary of MSNs in the biomedical field, beginning with a comprehensive overview of their development history. We then discuss the types of MSNs-based nanostructured architectures, as well as the classification of MSNs-based nanocomposites according to the elements existed in various inorganic functional components. Subsequently, we summarize the primary purposes of surface-functionalized modifications of MSNs. In the following, we discuss the biomedical applications of MSNs, and highlight the MSNs-based targeted therapeutic modalities currently developed. Given the importance of clinical translation, we also summarize the progress of MSNs in clinical trials. Finally, we take a perspective on the future direction and remaining challenges of MSNs in the biomedical field.
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Affiliation(s)
- Bolong Xu
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Organic-Inorganic Composites, Bionanomaterials & Translational Engineering Laboratory, Beijing Key Laboratory of Bioprocess, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, 100029, Beijing, China
| | - Shanshan Li
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Organic-Inorganic Composites, Bionanomaterials & Translational Engineering Laboratory, Beijing Key Laboratory of Bioprocess, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, 100029, Beijing, China
| | - Rui Shi
- National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, 100035, Beijing, China.
| | - Huiyu Liu
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Organic-Inorganic Composites, Bionanomaterials & Translational Engineering Laboratory, Beijing Key Laboratory of Bioprocess, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, 100029, Beijing, China.
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14
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Dong HQ, Fu XF, Wang MY, Zhu J. Research progress on reactive oxygen species production mechanisms in tumor sonodynamic therapy. World J Clin Cases 2023; 11:5193-5203. [PMID: 37621595 PMCID: PMC10445077 DOI: 10.12998/wjcc.v11.i22.5193] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 04/27/2023] [Accepted: 05/22/2023] [Indexed: 08/04/2023] Open
Abstract
In recent years, because of the growing desire to improve the noninvasiveness and safety of tumor treatments, sonodynamic therapy has gradually become a popular research topic. However, due to the complexity of the therapeutic process, the relevant mechanisms have not yet been fully elucidated. One of the widely accepted possibilities involves the effect of reactive oxygen species. In this review, the mechanism of reactive oxygen species production by sonodynamic therapy (SDT) and ways to enhance the sonodynamic production of reactive oxygen species are reviewed. Then, the clinical application and limitations of SDT are discussed. In conclusion, current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen, exhibit biological safety, and promote the clinical transformation of sonodynamic therapy.
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Affiliation(s)
- He-Qin Dong
- School of Medicine, Shaoxing University, Shaoxin 312000, Zhejiang Province, China
| | - Xiao-Feng Fu
- Department of Ultrasound, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
| | - Min-Yan Wang
- Department of Ultrasound, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
| | - Jiang Zhu
- Department of Ultrasound, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
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15
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Dong HQ, Fu XF, Wang MY, Zhu J. Research progress on reactive oxygen species production mechanisms in tumor sonodynamic therapy. World J Clin Cases 2023; 11:5187-5197. [DOI: 10.12998/wjcc.v11.i22.5187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 04/27/2023] [Accepted: 05/22/2023] [Indexed: 08/03/2023] Open
Abstract
In recent years, because of the growing desire to improve the noninvasiveness and safety of tumor treatments, sonodynamic therapy has gradually become a popular research topic. However, due to the complexity of the therapeutic process, the relevant mechanisms have not yet been fully elucidated. One of the widely accepted possibilities involves the effect of reactive oxygen species. In this review, the mechanism of reactive oxygen species production by sonodynamic therapy (SDT) and ways to enhance the sonodynamic production of reactive oxygen species are reviewed. Then, the clinical application and limitations of SDT are discussed. In conclusion, current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen, exhibit biological safety, and promote the clinical transformation of sonodynamic therapy.
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Affiliation(s)
- He-Qin Dong
- School of Medicine, Shaoxing University, Shaoxin 312000, Zhejiang Province, China
| | - Xiao-Feng Fu
- Department of Ultrasound, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
| | - Min-Yan Wang
- Department of Ultrasound, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
| | - Jiang Zhu
- Department of Ultrasound, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
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16
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Maleki A, Seyedhamzeh M, Yuan M, Agarwal T, Sharifi I, Mohammadi A, Kelicen-Uğur P, Hamidi M, Malaki M, Al Kheraif AA, Cheng Z, Lin J. Titanium-Based Nanoarchitectures for Sonodynamic Therapy-Involved Multimodal Treatments. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2023; 19:e2206253. [PMID: 36642806 DOI: 10.1002/smll.202206253] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 11/22/2022] [Indexed: 06/17/2023]
Abstract
Sonodynamic therapy (SDT) has considerably revolutionized the healthcare sector as a viable noninvasive therapeutic procedure. It employs a combination of low-intensity ultrasound and chemical entities, known as a sonosensitizer, to produce cytotoxic reactive oxygen species (ROS) for cancer and antimicrobial therapies. With nanotechnology, several unique nanoplatforms are introduced as a sonosensitizers, including, titanium-based nanomaterials, thanks to their high biocompatibility, catalytic efficiency, and customizable physicochemical features. Additionally, developing titanium-based sonosensitizers facilitates the integration of SDT with other treatment modalities (for example, chemotherapy, chemodynamic therapy, photodynamic therapy, photothermal therapy, and immunotherapy), hence increasing overall therapeutic results. This review summarizes the most recent developments in cancer therapy and tissue engineering using titanium nanoplatforms mediated SDT. The synthesis strategies and biosafety aspects of Titanium-based nanoplatforms for SDT are also discussed. Finally, various challenges and prospects for its further development and potential clinical translation are highlighted.
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Affiliation(s)
- Aziz Maleki
- Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), and Department of Pharmaceutical Nanotechnology School of pharmacy, Zanjan University of Medical Sciences, Zanjan, 4513956184, Iran
| | - Mohammad Seyedhamzeh
- Zanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), and Department of Pharmaceutical Nanotechnology School of pharmacy, Zanjan University of Medical Sciences, Zanjan, 4513956184, Iran
| | - Meng Yuan
- State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
| | - Tarun Agarwal
- Department of Bio-Technology, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Andhra Pradesh, 721302, India
| | - Ibrahim Sharifi
- Department of Materials Engineering, Faculty of Engineering, Shahrekord University, Shahrekord, 64165478, Iran
| | - Abbas Mohammadi
- Department of Chemistry, University of Isfahan, Isfahan, 81746-73441, Iran
| | - Pelin Kelicen-Uğur
- Faculty of Pharmacy, Department of Pharmacology, Hacettepe University, Sıhhiye, Ankara, 06430, Turkey
| | - Mehrdad Hamidi
- Department of Pharmaceutical Nanotechnology, School of pharmacy, Zanjan University of Medical Sciences, Zanjan, 4513956184, Iran
- Trita Nanomedicine Research & Technology Development Center (TNRTC), Zanjan Health Technology Park, Zanjan, 45156-13191, Iran
| | - Massoud Malaki
- Department of Mechanical Engineering, Faculty of Engineering, Isfahan University of Technology, Isfahan, Iran
| | - Abdulaziz A Al Kheraif
- Dental Health Department, College of Applied Medical Sciences, King Saud University, Riyadh, 12372, Saudi Arabia
| | - Ziyong Cheng
- State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
- Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Guangdong Medical University Key Laboratory of Research and Development of New Medical Materials, Dongguan, 523808, China
| | - Jun Lin
- State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China
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17
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Emerging nanosonosensitizers augment sonodynamic-mediated antimicrobial therapies. Mater Today Bio 2023; 19:100559. [PMID: 36798535 PMCID: PMC9926023 DOI: 10.1016/j.mtbio.2023.100559] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 01/07/2023] [Accepted: 01/19/2023] [Indexed: 01/22/2023] Open
Abstract
With the widespread prevalence of drug-resistant pathogens, traditional antibiotics have limited effectiveness and do not yield the desired outcomes. Recently, alternative antibacterial therapies based on ultrasound (US) have been explored to overcome the crisis of bacterial pathogens. Antimicrobial sonodynamic therapy (aSDT) offers an excellent solution that relies on US irradiation to produce reactive oxygen species (ROS) and achieve antibiotic-free mediated antimicrobial effects. In addition, aSDT possesses the advantage of superior tissue penetrability of US compared to light irradiation, demonstrating great feasibility in treating deep infections. Although existing conventional sonosensitizers can produce ROS for antimicrobial activity, some limitations, such as low penetration rate, nonspecific distribution and poor ROS production under hypoxic conditions, result in suboptimal sterilization in aSDT. Recently, emerging nanosonosensitizers have enormous advantages as high-performance agents in aSDT, which overcome the deficiencies of conventional sonosensitizers as described above. Thus, nanosonosensitizer-mediated aSDT has a bright future for the management of bacterial infections. This review classifies the current available nanosonosensitizers and provides an overview of the mechanisms, biomedical applications, recent advances and perspectives of aSDT.
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18
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Wang Y, Lu H, Wang X, Han L, Liu X, Cheng D, Yang F, Guo F, Wang W. Green tubular micro/nano architecture constructed by in-situ planting of small AgNPs on Kapok fiber for oil spill recovery, smart oil-water separation and multifunctional applications. Sep Purif Technol 2023. [DOI: 10.1016/j.seppur.2023.123278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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19
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Cao Z, Zhang X, Wei Z, Song C, Zou H, Ran J, Zhang H, Xie D, Han S, Wang Y, Cai Y, Han W. Thrombus-targeted nano-agents for NIR-II diagnostic fluorescence imaging-guided flap thromboembolism multi-model therapy. J Nanobiotechnology 2022; 20:447. [PMID: 36242039 PMCID: PMC9563174 DOI: 10.1186/s12951-022-01649-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 09/25/2022] [Indexed: 11/16/2022] Open
Abstract
In oral and maxillofacial surgery, flap repair is essential to the quality of postoperative life. Still, thrombosis is fatal for the survival of the flaps. Besides, some postoperative thrombotic diseases, such as pulmonary embolism, also intimidate patients’ life. The traditional diagnostic methods are still limited by a large amount of hardware and suffer from inconvenience, delay, and subjectivity. Moreover, the treatments mainly rely upon thrombolytics, such as urokinase (UK) plasminogen activator, which may cause bleeding risk, especially intracerebral hemorrhage. Herein, a kind of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing a first near-infrared window (NIR-I) phototheranostic agent Y8 and urokinase plasminogen activator (UK) as the core, and modified with the fibrin-targeting peptide Gly–Pro–Arg–Pro–Pro (GPRPP) were developed for the flap and postoperative thromboembolism treatment (named GPRPP-Y8U@P). The conjugated molecule Y8 endows GPRPP-Y8U@P with the capacity of NIR-II imaging and excellent photothermal/photodynamic therapeutic effects. In vivo experiments demonstrated that GPRPP-Y8U@P could quickly locate thrombus by NIR-II fluorescence imaging, and semi-quantitative analysis of the embolized blood vessels' paraffin section verified its thrombolytic efficiency. Additionally, the urokinase trapped in the NPs would not result in nonspecific bleeding, tremendously improving physical security and curative effects with minimizing side effects. Overall, the advantages of GPRPP-Y8U@P, such as precise localization of the thrombus, thrombus ablation in the site, and mild side effects, demonstrated the attractiveness of this approach for effective clinical monitoring of thrombus therapy.
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Affiliation(s)
- Zichen Cao
- Department of Oral Medicine, Nanjing Stomatological Hospital, Medical School of Nanjing University, 30 Zhongyang Road, Nanjing, 210008, China.,Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, 210008, China
| | - Xinyu Zhang
- Department of Oral Medicine, Nanjing Stomatological Hospital, Medical School of Nanjing University, 30 Zhongyang Road, Nanjing, 210008, China.,Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, 210008, China
| | - Zheng Wei
- Department of Oral Medicine, Nanjing Stomatological Hospital, Medical School of Nanjing University, 30 Zhongyang Road, Nanjing, 210008, China.,Pediatric Dentistry, Nanjing Stomatology hospital, Medical School of Nanjing University, No 30 Zhongyang road, Nanjing, 210008, China
| | - Chuanhui Song
- Institute of Translational Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China
| | - Huihui Zou
- Department of Oral Medicine, Nanjing Stomatological Hospital, Medical School of Nanjing University, 30 Zhongyang Road, Nanjing, 210008, China
| | - Jianchuan Ran
- Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, 210008, China
| | - Hongbo Zhang
- Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, 210008, China
| | - Diya Xie
- Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, 210008, China
| | - Shengwei Han
- Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, 210008, China
| | - Yufeng Wang
- Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, 210008, China
| | - Yu Cai
- Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, 310014, Zhejiang, China.
| | - Wei Han
- Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, 210008, China.
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21
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Liu Q, Zhang W, Jiao R, Lv Z, Lin X, Xiao Y, Zhang K. Rational Nanomedicine Design Enhances Clinically Physical Treatment-Inspired or Combined Immunotherapy. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2022; 9:e2203921. [PMID: 36002305 PMCID: PMC9561875 DOI: 10.1002/advs.202203921] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 08/03/2022] [Indexed: 05/19/2023]
Abstract
Independent of tumor type and non-invasive or minimally-invasive feature, current physical treatments including ultrasound therapy, microwave ablation (MWA), and radiofrequency ablation (RFA) are widely used as the local treatment methods in clinics for directly killing tumors and activating systematic immune responses. However, the activated immune responses are inadequate and incompetent for tumor recession, and the incomplete thermal ablation even aggravates the immunosuppressive tumor microenvironment (ITM), resulting in the intractable tumor recurrence and metastasis. Intriguingly, nanomedicine provides a powerful platform as they can elevate energy utilization efficiency and augment oncolytic effects for mitigating ITM and potentiating the systematic immune responses. Especially after combining with clinical immunotherapy, the anti-tumor killing effect by activating or enhancing the human anti-tumor immune system is reached, enabling the effective prevention against tumor recurrence and metastasis. This review systematically introduces the cutting-edge progress and direction of nanobiotechnologies and their corresponding nanomaterials. Moreover, the enhanced physical treatment efficiency against tumor progression, relapse, and metastasis via activating or potentiating the autologous immunity or combining with exogenous immunotherapeutic agents is exemplified, and their rationales are analyzed. This review offers general guidance or directions to enhance clinical physical treatment from the perspectives of immunity activation or magnification.
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Affiliation(s)
- Qiaoqiao Liu
- Department of RadiologyLiuzhou People's Hospital Affiliated to Guangxi Medical UniversityNo. 8 Wenchang RoadLiuzhou545006P. R. China
- Central LaboratoryShanghai Tenth People's HospitalTongji University School of MedicineShanghai200072P. R. China
- National Center for International Research of Bio‐targeting TheranosticsGuangxi Key Laboratory of Bio‐targeting TheranosticsGuangxi Medical UniversityNo. 22 Shuangyong Road 22Nanning530021P. R. China
| | - Wei Zhang
- Department of RadiologyLiuzhou People's Hospital Affiliated to Guangxi Medical UniversityNo. 8 Wenchang RoadLiuzhou545006P. R. China
| | - Rong Jiao
- National Center for International Research of Bio‐targeting TheranosticsGuangxi Key Laboratory of Bio‐targeting TheranosticsGuangxi Medical UniversityNo. 22 Shuangyong Road 22Nanning530021P. R. China
| | - Zheng Lv
- Department of RadiologyLiuzhou People's Hospital Affiliated to Guangxi Medical UniversityNo. 8 Wenchang RoadLiuzhou545006P. R. China
- Central LaboratoryShanghai Tenth People's HospitalTongji University School of MedicineShanghai200072P. R. China
| | - Xia Lin
- National Center for International Research of Bio‐targeting TheranosticsGuangxi Key Laboratory of Bio‐targeting TheranosticsGuangxi Medical UniversityNo. 22 Shuangyong Road 22Nanning530021P. R. China
| | - Yunping Xiao
- Department of RadiologyLiuzhou People's Hospital Affiliated to Guangxi Medical UniversityNo. 8 Wenchang RoadLiuzhou545006P. R. China
| | - Kun Zhang
- Department of RadiologyLiuzhou People's Hospital Affiliated to Guangxi Medical UniversityNo. 8 Wenchang RoadLiuzhou545006P. R. China
- Central LaboratoryShanghai Tenth People's HospitalTongji University School of MedicineShanghai200072P. R. China
- National Center for International Research of Bio‐targeting TheranosticsGuangxi Key Laboratory of Bio‐targeting TheranosticsGuangxi Medical UniversityNo. 22 Shuangyong Road 22Nanning530021P. R. China
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Zhao PH, Wu YL, Li XY, Feng LL, Zhang L, Zheng BY, Ke MR, Huang JD. Aggregation-Enhanced Sonodynamic Activity of Phthalocyanine-Artesunate Conjugates. Angew Chem Int Ed Engl 2022; 61:e202113506. [PMID: 34761489 DOI: 10.1002/anie.202113506] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/05/2021] [Indexed: 12/15/2022]
Abstract
The clinical prospect of sonodynamic therapy (SDT) has not been fully realized due to the scarcity of efficient sonosensitizers. Herein, we designed phthalocyanine-artesunate conjugates (e.g. ZnPcT4 A), which could generate up to ca. 10-fold more reactive oxygen species (ROS) than the known sonosensitizer protoporphyrin IX. Meanwhile, an interesting and significant finding of aggregation-enhanced sonodynamic activity (AESA) was observed for the first time. ZnPcT4 A showed about 60-fold higher sonodynamic ROS generation in the aggregated form than in the disaggregated form in aqueous solutions. That could be attributed to the boosted ultrasonic cavitation of nanostructures. The level of the AESA effect depended on the aggregation ability of sonosensitizer molecules and the particle size of their aggregates. Moreover, biological studies demonstrated that ZnPcT4 A had high anticancer activities and biosafety. This study thus opens up a new avenue the development of efficient organic sonosensitizers.
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Affiliation(s)
- Peng-Hui Zhao
- College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian, 350108, China
| | - Yu-Lin Wu
- College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian, 350108, China
| | - Xue-Yan Li
- College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian, 350108, China
| | - Lin-Lin Feng
- College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian, 350108, China
| | - Ling Zhang
- College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian, 350108, China
| | - Bi-Yuan Zheng
- College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian, 350108, China
| | - Mei-Rong Ke
- College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian, 350108, China
| | - Jian-Dong Huang
- College of Chemistry, State Key Laboratory of Photocatalysis on Energy and Environment, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian, 350108, China
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Zhao P, Wu Y, Li X, Feng L, Zhang L, Zheng B, Ke M, Huang J. Aggregation‐Enhanced Sonodynamic Activity of Phthalocyanine–Artesunate Conjugates. Angew Chem Int Ed Engl 2022. [DOI: 10.1002/ange.202113506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Peng‐Hui Zhao
- College of Chemistry State Key Laboratory of Photocatalysis on Energy and Environment Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy Fuzhou University Fuzhou Fujian 350108 China
| | - Yu‐Lin Wu
- College of Chemistry State Key Laboratory of Photocatalysis on Energy and Environment Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy Fuzhou University Fuzhou Fujian 350108 China
| | - Xue‐Yan Li
- College of Chemistry State Key Laboratory of Photocatalysis on Energy and Environment Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy Fuzhou University Fuzhou Fujian 350108 China
| | - Lin‐Lin Feng
- College of Chemistry State Key Laboratory of Photocatalysis on Energy and Environment Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy Fuzhou University Fuzhou Fujian 350108 China
| | - Ling Zhang
- College of Chemistry State Key Laboratory of Photocatalysis on Energy and Environment Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy Fuzhou University Fuzhou Fujian 350108 China
| | - Bi‐Yuan Zheng
- College of Chemistry State Key Laboratory of Photocatalysis on Energy and Environment Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy Fuzhou University Fuzhou Fujian 350108 China
| | - Mei‐Rong Ke
- College of Chemistry State Key Laboratory of Photocatalysis on Energy and Environment Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy Fuzhou University Fuzhou Fujian 350108 China
| | - Jian‐Dong Huang
- College of Chemistry State Key Laboratory of Photocatalysis on Energy and Environment Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy Fuzhou University Fuzhou Fujian 350108 China
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Sabuncu S, Yildirim A. Gas-stabilizing nanoparticles for ultrasound imaging and therapy of cancer. NANO CONVERGENCE 2021; 8:39. [PMID: 34851458 PMCID: PMC8636532 DOI: 10.1186/s40580-021-00287-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 11/05/2021] [Indexed: 05/06/2023]
Abstract
The use of ultrasound in the clinic has been long established for cancer detection and image-guided tissue biopsies. In addition, ultrasound-based methods have been widely explored to develop more effective cancer therapies such as localized drug delivery, sonodynamic therapy, and focused ultrasound surgery. Stabilized fluorocarbon microbubbles have been in use as contrast agents for ultrasound imaging in the clinic for several decades. It is also known that microbubble cavitation could generate thermal, mechanical, and chemical effects in the tissue to improve ultrasound-based therapies. However, the large size, poor stability, and short-term cavitation activity of microbubbles limit their applications in cancer imaging and therapy. This review will focus on an alternative type of ultrasound responsive material; gas-stabilizing nanoparticles, which can address the limitations of microbubbles with their nanoscale size, robustness, and high cavitation activity. This review will be of interest to researchers who wish to explore new agents to develop improved methods for molecular ultrasound imaging and therapy of cancer.
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Affiliation(s)
- Sinan Sabuncu
- CEDAR, Knight Cancer Institute, School of Medicine, Oregon Health & Science University, Portland, OR, 97201, USA
| | - Adem Yildirim
- CEDAR, Knight Cancer Institute, School of Medicine, Oregon Health & Science University, Portland, OR, 97201, USA.
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Zhou QM, Lu YF, Zhou JP, Yang XY, Wang XJ, Yu JN, Du YZ, Yu RS. Self-amplification of oxidative stress with tumour microenvironment-activatable iron-doped nanoplatform for targeting hepatocellular carcinoma synergistic cascade therapy and diagnosis. J Nanobiotechnology 2021; 19:361. [PMID: 34749740 PMCID: PMC8576982 DOI: 10.1186/s12951-021-01102-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Accepted: 10/21/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma is insensitive to many chemotherapeutic agents. Ferroptosis is a form of programmed cell death with a Fenton reaction mechanism. It converts endogenous hydrogen peroxide into highly toxic hydroxyl radicals, which inhibit hepatocellular carcinoma progression. METHODS The morphology, elemental composition, and tumour microenvironment responses of various organic/inorganic nanoplatforms were characterised by different analytical methods. Their in vivo and in vitro tumour-targeting efficacy and imaging capability were analysed by magnetic resonance imaging. Confocal microscopy, flow cytometry, and western blotting were used to investigate the therapeutic efficacy and mechanisms of complementary ferroptosis/apoptosis mediated by the nanoplatforms. RESULTS The nanoplatform consisted of a silica shell doped with iron and disulphide bonds and an etched core loaded with doxorubicin that generates hydrogen peroxide in situ and enhances ferroptosis. It relied upon transferrin for targeted drug delivery and could be activated by the tumour microenvironment. Glutathione-responsive biodegradability could operate synergistically with the therapeutic interaction between doxorubicin and iron and induce tumour cell death through complementary ferroptosis and apoptosis. The nanoplatform also has a superparamagnetic framework that could serve to guide and monitor treatment under T2-weighted magnetic resonance imaging. CONCLUSION This rationally designed nanoplatform is expected to integrate cancer diagnosis, treatment, and monitoring and provide a novel clinical antitumour therapeutic strategy.
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Affiliation(s)
- Qiao-Mei Zhou
- Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang Province, People's Republic of China
| | - Yuan-Fei Lu
- Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang Province, People's Republic of China
| | - Jia-Ping Zhou
- Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang Province, People's Republic of China
| | - Xiao-Yan Yang
- Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang Province, People's Republic of China
| | - Xiao-Jie Wang
- Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang Province, People's Republic of China
| | - Jie-Ni Yu
- Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang Province, People's Republic of China
| | - Yong-Zhong Du
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang Province, People's Republic of China.
| | - Ri-Sheng Yu
- Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang Province, People's Republic of China.
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Zhang H, Pan X, Wu Q, Guo J, Wang C, Liu H. Manganese carbonate nanoparticles-mediated mitochondrial dysfunction for enhanced sonodynamic therapy. EXPLORATION (BEIJING, CHINA) 2021; 1:20210010. [PMID: 37323218 PMCID: PMC10190974 DOI: 10.1002/exp.20210010] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 08/04/2021] [Indexed: 06/13/2023]
Abstract
Sonodynamic therapy (SDT) has attracted widespread attention due to its non-invasiveness and deep tissue penetration. However, the development of efficient sonodynamic nanoplatforms to improve the therapeutic efficiency is still one of the main challenges of current research. In this work, a new type of sonosensitizer prepared by a simple method, manganese carbonate nanoparticles (MnCO3 NPs), is used for enhanced SDT. MnCO3 NPs could generate large amounts of 1O2 and •OH under ultrasound irradiation. At the same time, CO2 and Mn ions could be released in a weak acid environment due to the excellent degradability of MnCO3 NPs. The CO2 bubbles caused cell necrosis by ultrasonic cavitation and used for ultrasound imaging. And Mn ions activated the mitochondrial cell apoptosis pathway. In vivo experiments proved that this sonosensitizer with mitochondrial regulatory capacity showed high tumor inhibition rates for enhanced sonodynamic tumor therapy.
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Affiliation(s)
- Haoyuan Zhang
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Organic–Inorganic Composites, Beijing Laboratory of Biomedical Materials, Bionanomaterials & Translational Engineering Laboratory, Beijing Key Laboratory of BioprocessBeijing University of Chemical TechnologyBeijingP. R. China
| | - Xueting Pan
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Organic–Inorganic Composites, Beijing Laboratory of Biomedical Materials, Bionanomaterials & Translational Engineering Laboratory, Beijing Key Laboratory of BioprocessBeijing University of Chemical TechnologyBeijingP. R. China
| | - Qingyuan Wu
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Organic–Inorganic Composites, Beijing Laboratory of Biomedical Materials, Bionanomaterials & Translational Engineering Laboratory, Beijing Key Laboratory of BioprocessBeijing University of Chemical TechnologyBeijingP. R. China
| | - Juan Guo
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Organic–Inorganic Composites, Beijing Laboratory of Biomedical Materials, Bionanomaterials & Translational Engineering Laboratory, Beijing Key Laboratory of BioprocessBeijing University of Chemical TechnologyBeijingP. R. China
| | - Chaohui Wang
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Organic–Inorganic Composites, Beijing Laboratory of Biomedical Materials, Bionanomaterials & Translational Engineering Laboratory, Beijing Key Laboratory of BioprocessBeijing University of Chemical TechnologyBeijingP. R. China
| | - Huiyu Liu
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Organic–Inorganic Composites, Beijing Laboratory of Biomedical Materials, Bionanomaterials & Translational Engineering Laboratory, Beijing Key Laboratory of BioprocessBeijing University of Chemical TechnologyBeijingP. R. China
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