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Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers

Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 49-68页

作者： xumei ouyang Yu Liu Ke Zheng Zhiqing Pang Shaojun Peng Zhuhai Institute of Translational Medicine Zhuhai Precision Medical CenterZhuhai People’s Hospital(Zhuhai Hospital Affiliated with Jinan University)Zhuhai 519000China Key Laboratory of Smart Drug Delivery Ministry of EducationDepartment of PharmaceuticsSchool of PharmacyFudan UniversityShanghai 201203China School of Materials Science and Engineering Dongguan University of TechnologyDongguan 523808China

Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment.Polyethylene glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological environment.However,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications.Zwitterionic polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility.Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues.More impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications.The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical translation.Herein,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlyingmechanisms.Finally,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.

关键词： Zwitterionic polymer Nano drug delivery system Biological barrier Targeting delivery Disease treatment

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Rapid sterilisation and diabetic cutaneous regeneration using cascade bio-heterojunctions through glucose oxidase-primed therapy

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Bioactive Materials 2023年第7期25卷 748-765页

作者： Yi Deng xumei ouyang Jiyu Sun Xiuyuan Shi Yunfei Li Yau Kei Chan Weizhong Yang Shaojun Peng College of Biomedical Engineering School of Chemical EngineeringSichuan UniversityChengdu610065China State Key Laboratory of Polymer Materials Engineering Sichuan UniversityChengdu610065China Zhuhai Institute of Translational Medicine Zhuhai People’s Hospital(Zhuhai Hospital Affiliated with Jinan University)ZhuhaiGuangdong519000China State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu610041China Department of Materials Imperial College LondonSW72AZLondonUnited Kingdom Department of Biomedical Engineering The City College of the City University of New YorkNew YorkUnited States Department of Mechanical Engineering The University of Hong KongHong KongChina Department of Ophthalmology The University of Hong KongHong KongChina

The cutaneous wound in diabetic patients frequently encounters intractable pathogenic infections due to the hyperglycemia micromilieu which is conducive to bacterial growth and multiplication.Despite the extensive clinical use of antibiotics to treat bacterial infections,the emergence of drug-resistant and super pathogens as well as the potential side effects of antibiotics have elicited alarming challenges to public health.To address this daunting concern,we devise and develop a photo-activated cascade bio-heterojunctions(C-bio-HJs)for rapid sterilization and diabetic cutaneous regeneration.In the designed C-bio-HJs,photo-generated electron-hole pairs of graphite-phase carbon nitride(g-C_(3)N_(4))are effectively separated with the marriage of molybdenum disulfide(MoS_(2)),which achieves the augmented photodynamic antibacterial effect.Moreover,glucose oxidase(GOx)tethered on the bio-HJs catalyzes glucose into hydrogen peroxide(H_(2)O_(2))in diabetic wounds for starvation therapy.Furthermore,Mo4+enables the catalysis of H_(2)O_(2)into a highly effective hydroxyl radical(⋅OH)for chemodynamic-photothermal combined antibacterial therapy.Both in vitro and in vivo results authenticate the cascading antibacterial properties and skin regeneration-promoting effects of the C-bio-HJs,which provide a facile strategy to combat diabetic wound healing through the synergistic GOx-primed dynamic therapies.

关键词： Antibacterial therapy Bio-heterojunction g-C_(3)N_(4) Rapid sterilization Tissue regeneration

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基于间充质干细胞的小分子化学药物肿瘤靶向递送系统研究进展

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浙江大学学报（医学版） 2018年第5期47卷 525-533页

作者：王晓玲欧阳旭梅孙晓译浙江大学城市学院医学院药学系浙江杭州310015 浙江大学药学院浙江杭州310058

近年来,大量研究通过细胞内化或细胞膜结合的方式将生物大分子或小分子化学药物负载于间充质干细胞(MSC)上,利用其天然的肿瘤归巢特性实现药物的靶向递送,继而通过在靶部位药物的释放或基因表达,达到肿瘤治疗的目的。基因修饰MSC的研究... 详细信息

近年来,大量研究通过细胞内化或细胞膜结合的方式将生物大分子或小分子化学药物负载于间充质干细胞(MSC)上,利用其天然的肿瘤归巢特性实现药物的靶向递送,继而通过在靶部位药物的释放或基因表达,达到肿瘤治疗的目的。基因修饰MSC的研究较为成熟,而递送小分子化学药物的研究起步较晚。本文从MSC肿瘤迁移机制、细胞注射后体内分布特点入手,总结了MSC在小分子化学药物肿瘤靶向递送中的研究;同时介绍了MSC与原型药物、载药纳米粒构建的复合系统的载药、释药过程,展望了该系统遇到的挑战和应用前景。

关键词：肿瘤间质干细胞/细胞学纳米球抗肿瘤药药物释放系统综述

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