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Biodegradable polymeric nanoparticles based on amphiphilic principle:construction and application in drug delivery

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Science China Chemistry 2014年第4期57卷 461-475页

作者： ZHANG ShiYong WU Yao HE Bin luo kui GU ZhongWei National Engineering Research Center for Biomaterials Sichuan University

The use of nanotechnology in drug-delivery systems(DDS) is attractive for advanced diagnosis and treatment of cancer diseases. Biodegradable polymeric nanoparticles, for example, have promising applications as advanced drug carriers in cancer treatment. In this review, we discuss the development of drug-delivery systems based on an amphiphilic principle mainly conducted by our group for anti-cancer drug delivery. We first briefly address the synthetic chemistry for amphiphilic biodegradable polymers. In the second part, we summarize progress in the application of self-assembled polymer micelles using amphiphilic biodegradable copolymers as anti-tumor drug carriers.

关键词： biodegradable polymer miceUe amphiphilicity drug-delivery system cancer

Enhancing drug penetration in solid tumors via nanomedicine:Evaluation models,strategies and perspectives

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Bioactive Materials 2024年第2期32卷 445-472页

作者： Xiaoding Shen Dayi Pan Qiyong Gong Zhongwei Gu kui luo Department of Radiology Huaxi MR Research Center(HMRRC)Frontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China Hospital Sichuan UniversityChengdu610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen361021China

Effective tumor treatment depends on optimizing drug penetration and accumulation in tumor tissue while minimizing systemic *** has emerged as a key solution that addresses the rapid clearance of free drugs,but achieving deep drug penetration into solid tumors remains *** review discusses various strategies to enhance drug penetration,including manipulation of the tumor microenvironment,exploitation of both external and internal stimuli,pioneering nanocarrier surface engineering,and development of innovative tactics for active tumor *** outstanding strategy is organelle-affinitive transfer,which exploits the unique properties of specific tumor cell organelles and heralds a potentially transformative approach to active transcellular transfer for deep tumor *** models are essential to evaluate the efficacy of these *** patient-derived xenograft(PDX)model is gaining traction as a bridge between laboratory discovery and clinical ***,the journey from bench to bedside for nanomedicines is fraught with *** efforts should prioritize deepening our understanding of nanoparticle-tumor interactions,re-evaluating the EPR effect,and exploring novel nanoparticle transport mechanisms.

关键词： Nanomedicine Tumor penetration Penetration models Tumor microenvironment Organelle-affinitive transfer

Constant Barrier Strategies in a Two-state Markov-modulated Dual Risk Model

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Acta Mathematicae Applicatae Sinica 2011年第4期27卷 679-690页

作者： Xue-min MA kui luo Guang-ming WANG Yi-jun HU School of Mathematics and Statistics Wuhan University Wuhan 430072 China

In this paper, we consider the dividend problem in a two-state Markov-modulated dual risk model, in which the gain arrivals, gain sizes and expenses are influenced by a Markov process. A system of integro-differential equations for the expected value of the discounted dividends until ruin is derived. In the case of exponential gain sizes, the equations are solved and the best barrier is obtained via numerical example. Finally, using numerical example, we compare the best barrier and the expected discounted dividends in the two-state Markov-modulated dual risk model with those in an associated averaged compound Poisson risk model. Numerical results suggest that one could use the results of the associated averaged compound Poisson risk model to approximate those for the two-state Markov-modulated dual risk model.

关键词： Dual risk model Markov-modulated risk model barrier strategy

Cox Risk Model with Correlated Classes of Business

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Wuhan University Journal of Natural Sciences 2009年第5期14卷 378-382页

作者： luo kui WANG Guangming HU Yijun Industrial Training Centre Shenzhen Polytechnic Shenzhen 518055 Guangdong China School of Mathematics and Statistics Wuhan University Wuhan 430072 Hubei China

A correlated aggregate claim model with m dependent classes of insurance business is constructed, in which claim occurrences of m classes relate to Cox process and these claim processes are correlated. This Cox risk model with correlated classes of business is first transformed to the Cox model of n independent risk processes. Then the generalized Lundberg exponent and Lundberg inequality are obtained by the martingale approach. Finally, the explicit expression of Lundberg exponent under a special condition is derived.

关键词： Cox process Lundberg inequality ruin probability martingale

Stability and Accuracy Considerations in the Design and Implementation of Wind Turbine Power Hardware in the Loop Platform

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CSEE Journal of Power and Energy Systems 2017年第2期3卷 167-175页

作者： kui luo Wenhui Shi Yongning Chi Qiuwei Wu Weisheng Wang State Key Laboratory of Operation and Control of Renewable Energy&Storage System China Electric Power Research Institute(CEPRI)Beijing 100192China Center for Electric Power and Energy(CEE) Department of Electrical EngineeringTechnical University of Denmark(DTU)Kgs.Lyngby 2800Denmark

There is increasing interest in the evaluation of wind turbine control capabilities for providing grid *** hardware in the loop(PHIL)simulation is an advanced method that can be used for studying the interaction of hardware with the power network,as the scaled-down actual wind turbine is connected with a simulated system through an *** consideration must be made in the design of the PHIL platform to ensure that the system is stable and yields accurate *** paper presents a method for stabilizing the PHIL interface and improving the accuracy of PHIL simulation in a real-time *** method factors in both the power and voltage scaling level,and a phase compensation *** uses the reactive power control capability of the wind turbine inverter to eliminate the phase shift imposed by the feedback current *** is accomplished with no negative impact on the dynamic behavior of the wind *** PHIL simulation results demonstrate the effectiveness of the proposed stability analysis method and phase compensation *** strength of the platform is demonstrated by extending the simulation method to wind turbine control validation.

关键词： Phase compensation power hardware in the loop stability and accuracy wind turbine

GSH-sensitive polymeric prodrug: Synthesis and loading with photosensitizers as nanoscale chemo-photodynamic anti-cancer nanomedicine

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Acta Pharmaceutica Sinica B 2022年第1期12卷 424-436页

作者： Lei luo Yiming Qi Hong Zhong Shinan Jiang Hu Zhang Hao Cai Yahui Wu Zhongwei Gu Qiyong Gong kui luo Huaxi MR Research Center(HMRRC) Department of RadiologyFunctional and Molecular Imaging Key Laboratory of Sichuan ProvinceNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China College of Pharmaceutical Sciences Southwest UniversityChongqing 400716China Research Unit of Psychoradiology Chinese Academy of Medical SciencesChengdu 610041China Amgen Bioprocessing Centre Keck Graduate InstituteClaremontCA 91711USA

Precisely delivering combinational therapeutic agents has become a crucial challenge for anti-tumor treatment. In this study, a novel redox-responsive polymeric prodrug(molecular weight,MW: 93.5 k Da) was produced by reversible addition-fragmentation chain transfer(RAFT) polymerization. The amphiphilic block polymer-doxorubicin(DOX) prodrug was employed to deliver a hydrophobic photosensitizer(PS), chlorin e6(Ce6), and the as-prepared nanoscale system [NPs(Ce6)] was investigated as a chemo-photodynamic anti-cancer agent. The glutathione(GSH)-cleavable disulfide bond was inserted into the backbone of the polymer for biodegradation inside tumor cells, and DOX conjugated onto the polymer with a disulfide bond was successfully released intracellularly. NPs(Ce6) released DOX and Ce6 with their original molecular structures and degraded into segments with low MWs of 41.2 k Da in the presence of GSH. NPs(Ce6) showed a chemo-photodynamic therapeutic effect to kill 4 T1 murine breast cancer cells, which was confirmed from a collapsed cell morphology, a lifted level in the intracellular reactive oxygen species, a reduced viability and induced apoptosis. Moreover, ex vivo fluorescence images indicated that NPs(Ce6) retained in the tumor, and exhibited a remarkable in vivo anticancer efficacy. The combinational therapy showed a significantly increased tumor growth inhibition(TGI,58.53%). Therefore, the redox-responsive, amphiphilic block polymeric prodrug could have a great potential as a chemo-photodynamic anti-cancer agent.

关键词： Stimuli responsiveness Polymeric prodrug Photodynamic therapy Combinational therapy Nanomedicine

Dendron-polymer hybrid mediated anticancer drug delivery for suppression of mammary cancer

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Journal of Materials Science & Technology 2021年第4期63卷 115-123页

作者： Dayi Pan Xiuli Zheng Miao Chen Qianfeng Zhang Zhiqian Li Zhenyu Duan Qiyong Gong Zhongwei Gu Hu Zhang kui luo Huaxi MR Research Center(HMRRC) Department of RadiologyFunctional and Molecular Imaging Key Laboratory of Sichuan ProvinceNational Clinical Research Center for GeriatricsState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China Department of Orthodontics West China Hospital of StomatologySichuan UniversityChengdu610041SichuanChina Amegen Bioprocessing Centre Keck Graduate InstituteCA91711USA

Dendron-polymer-based nanoscale and stimuli-responsive drug delivery systems have shown great promise in tumor-targeting accumulation without significant *** we report a dendronized polymer-doxorubicin(DOX)hybrid(DPDH)with an improved in vivo drug delivery efficiency for cancer therapy compared with a linear polymer-DOX conjugate(LPDC).The in vitro drug release profile of DOX indicates that DPDH displays pH-responsive drug release due to cleavage of hydrazone bonds since a greater amount of DOX is released at pH 5.2 at a faster rate than at pH *** efficiently enters 4 T1 cells and releases DOX to induce cytotoxicity and *** to the dendronzied structure,DPDH has a significantly longer blood circulation time than *** substantially enhances the therapeutic efficacy to suppress tumor growth in a 4 T1 mammary cancer model than LPDC as well as free drug,evidenced from tumor growth inhibition,TUNEL assessment and histological *** of DPDH is also confirmed from hemolysis,body weight shifts during treatment and pathological *** study demonstrates the use of dendronized polymer-DOX hybrids for specific drug molecules is a promising approach for drug delivery.

关键词： cancer analysis. release

Cathepsin B-responsive and gadolinium-labeled branched glycopolymer-PTX conjugate-derived nanotheranostics for cancer treatment

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Acta Pharmaceutica Sinica B 2021年第2期11卷 544-559页

作者： Hao Cai Yufan Xiang Yujun Zeng Zhiqian Li Xiuli Zheng Qiang luo Hongyan Zhu Qiyong Gong Zhongwei Gu Yanhui Liu Hu Zhang kui luo Huaxi MR Research Center(HMRRC) Department of Neurosurgeryand Department of RadiologyFunctional and Molecular Imaging Key Laboratory of Sichuan ProvinceWest China HospitalSichuan UniversityChengdu 610041China Laboratory of Stem Cell Biology West China HospitalSichuan UniversityChengdu 610041China Amgen Bioprocessing Centre Keck Graduate InstituteClaremontCA 91711USA

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of *** carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment.A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate,conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a(Ppa)with a branched *** branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B,and PTX was simultaneously released to exert its therapeutic *** theranostic nanomedicine,branched glycopolymer-PTX-DOTA-Gd,had an extended circulation time,enhanced accumulation in tumors,and excellent biocompatibility with significantly reduced gadolinium ion(Gd3+)retention after 96 h *** imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90%were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic *** branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer.

关键词： Stimuli-responsive Drug delivery Branched glycopolymers Biodegradability Nanomedicine Theranostics

Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2194-2209页

作者： Zhilin Li Qianfeng Zhang Zhiqian Li Long Ren Dayi Pan Qiyong Gong Zhongwei Gu Hao Cai kui luo Department of Radiology Huaxi MR Research Center(HMRRC)Clinical Research Center for BreastDepartment of Breast SurgeryDepartment of Thoracic Surgery and Institute of Thoracic OncologyFrontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China Hospital Sichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Key Laboratory of Research and Development for Natural ProductsSchool of PharmacyYunnan UniversityKunming 650500China

Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their *** address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor *** this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into *** internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP ***,diABZI effectively activated the STING *** with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

关键词： Glycopolymer Polymer prodrug Immunogenic cell death Nanoassembly Epirubicin STING pathway Immuno-supportive microenvironment Immunotherapy