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Multifunctional biodegradable nanoplatform based on oxaliplatin prodrug cross-linked mesoporous polydopamine for enhancing cancer synergetic therapy

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Chinese Chemical Letters 2024年第1期35卷 379-384页

作者： Ping Sun Zimu Li Dan Zhang Wenfeng Zeng Yi Zheng Lin Mei hongzhong chen Nansha Gao Xiaowei Zeng School of Pharmaceutical Sciences(Shenzhen) Sun Yat-sen UniversityShenzhen 518107China Central Laboratory University of Chinese Academy of Sciences-Shenzhen HospitalShenzhen 518106China Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300192China

Due to the limitations of conventional chemotherapy including side effects,poor prognosis,and drug resistance,there is an urgent need for the development of a novel multi-functional combined therapy strategy.Dopamine-modified oxaliplatin prodrug(OXA-DA)was successfully synthesized in this study to ameliorate the organ distribution of oxaliplatin for improving the drug efficacy and reducing toxic side effects,and OXA-DA was applied to develop a porous oxaliplatin cross-linked polydopamine nanoparticle for loading siPD-L1 to construct multifunctional nanoplatform.The multifunctional nanoplatform was modified with poly(2-ethyl-2-oxazoline)(PEOz),which occurred charge reversal in the tumor microenvironment,and exerted the lysosomal escape effect in tumor cells to improve the bioavailability of small interfering RNA targeting programmed cell death-ligand 1(siPD-L1).The pH-responsive charge reversal,photothermal,biodegradation,lysosomal escape ability,PD-L1 protein degradation,toxicity properties and multiple antitumor effects were comprehensively evaluated in vitro and in vivo experiments.The findings indicated that OXA-DA-siPD-L1@PDA-PEOz excellently induced tumor cell necrosis and apoptosis as a result of the synergistic effect of chemo-photothermal therapy,and upregulated CD8+T cells produced interferon-γ(IFN-γ)to further attack the tumor cells.In conclusion,the novel nanoplatform-mediated chemo/photothermal/immunotherapy has promising clinical applications in the treatment of malignant tumors.

关键词： Oxaliplatin prodrug Mesoporous polydopamine Charge reversal Synergetic therapy Cancer nanotechnology

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Polymeric microneedle-mediated sustained release systems: Design strategies and promising applications for drug delivery

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Asian Journal of Pharmaceutical Sciences 2022年第1期17卷 70-86页

作者： Li Yang Yao Yang hongzhong chen Lin Mei Xiaowei Zeng Institute of Pharmaceutics School of Pharmaceutical Sciences(Shenzhen)Sun Yat-sen UniversityShenzhen 518107China Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China

Parenteral sustained release drug formulations, acting as preferable platforms for longterm exposure therapy, have been wildly used in clinical practice. However, most of these delivery systems must be given by hypodermic injection. Therefore, issues including needle-phobic, needle-stick injuries and inappropriate reuse of needles would hamper the further applications of these delivery platforms. Microneedles (MNs) as a potential alternative system for hypodermic needles can benefit from minimally invasive and self-administration. Recently, polymeric microneedle-mediated sustained release systems (MN@SRS) have opened up a new way for treatment of many diseases. Here, we reviewed the recent researches in MN@SRS for transdermal delivery, and summed up its typical design strategies and applications in various diseases therapy, particularly focusing on the applications in contraception, infection, cancer, diabetes, and subcutaneous disease. An overview of the present clinical translation difficulties and future outlook of MN@SRS was also provided.

关键词： Transdermal drug delivery Microneedles Sustained release Long-term exposure therapy

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Polyphenol-based hydrogels: Pyramid evolution from crosslinked structures to biomedical applications and the reverse design

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Bioactive Materials 2022年第11期7卷 49-70页

作者： Zimu Li Zhidong chen hongzhong chen Kebing chen Wei Tao Xiao-kun Ouyang Lin Mei Xiaowei Zeng Institute of Pharmaceutics School of Pharmaceutical Sciences(Shenzhen)Sun Yat-sen UniversityShenzhen518107China Department of Spine Surgery Center for Orthopaedic SurgeryThe Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhou510655China Center for Nanomedicine Brigham and Women’s HospitalHarvard Medical SchoolBostonMA02115United States School of Food and Pharmacy Zhejiang Ocean UniversityZhoushan316022China

As a kind of nature-derived bioactive materials, polyphenol-based hydrogels possess many unique and outstanding properties such as adhesion, toughness, and self-healing due to their specific crosslinking structures, which have been widely used in biomedical fields including wound healing, antitumor, treatment of motor system injury, digestive system disease, oculopathy, and bioelectronics. In this review, starting with the classi-fication of common polyphenol-based hydrogels, the pyramid evolution process of polyphenol-based hydrogels from crosslinking structures to derived properties and then to biomedical applications is elaborated, as well as the efficient reverse design considerations of polyphenol-based hydrogel systems are proposed. Finally, the existing problems and development prospects of these hydrogel materials are discussed. It is hoped that the unique perspective of the review can promote further innovation and breakthroughs of polyphenol-based hydrogels in the future.

关键词： Biomaterials Adhesive hydrogels Polyphenol Disease treatment Reverse design

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Actively separated microneedle patch for sustained-release of growth hormone to treat growth hormone deficiency

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Acta Pharmaceutica Sinica B 2023年第1期13卷 344-358页

作者： Li Yang Qingyun Liu Xinhui Wang Nansha Gao Xiuzhen Li hongzhong chen Lin Mei Xiaowei Zeng Institute of Pharmaceutics School of Pharmaceutical Sciences(Shenzhen)Sun Yat-sen UniversityShenzhen 518107China Department of Genetics and Endocrinology Guangzhou Women and Children's Medical CenterGuangzhou 510623China Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical SciencesPeking Union Medical CollegeTianjin 300192China

Growth hormone deficiency(GHD)has become a serious healthcare burden,and presents a huge impact on the physical and mental health of patients.Here,we developed an actively separated microneedle patch(PAA/NaHCO_(3)^(-)Silk MN)based on silk protein for sustained release of recombinant human growth hormone(rhGH).Silk protein,as a friendly carrier material for proteins,could be constructed in mild full-water conditions and ensure the activity of rhGH.After manually pressing PAA/NaHCO_(3)^(-)Silk MN patch to skin for 1 min,active separation is achieved by absorbing the interstitial fluid(ISF)to trigger HCO_(3)^(-)in the active backing layer to produce carbon dioxide gas(CO_(2)).In rats,the MN patch could maintain the sustained release of rhGH for more than 7 days,and produce similar effects as daily subcutaneous(S.C.)injections of rhGH in promoting height and weight with well tolerated.Moreover,the PAA/NaHCO_(3)^(-)Silk MN patch with the potential of painless self-administration,does not require cold chain transportation and storage possess great economic benefits.Overall,the PAA/NaHCO_(3)^(-)Silk MN patch can significantly improve patient compliance and increase the availability of drugs,meet current unmet clinical needs,improve clinical treatment effects of GHD patients.

关键词： Microneedle Silk protein Self-administration Sustained-release Actively separated Growth hormone deficiency Growth hormone Long-acting GH

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An Intelligent IEQ Monitoring and Feedback System:Development and Applications

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Engineering 2022年第11期18卷 218-231页

作者： Yang Geng Zhongchen Zhang Juan Yu hongzhong chen Hao Zhou Borong Lin Weimin Zhuang School of Architecture Tsinghua UniversityBeijing 100084China Key Laboratory of Eco Planning and Green Building Ministry of EducationTsinghua UniversityBeijing 100084China Beijing Key Laboratory of Indoor Air Quality Evaluation and Control Tsinghua UniversityBeijing 100084China Architectural Design and Research Institute of Tsinghua University Beijing 100084China Beijing Tsinghua Tongheng Urban Planning and Design Institute Beijing 100085China

Indoor environmental quality(IEQ)significantly affects human health and wellbeing.Therefore,continuous IEQ monitoring and feedback is of great concern in both the industrial and academic communities.However,most existing studies only focus on developing sensors that cost-effectively promote IEQ measurement while ignoring interactions between the human side and IEQ monitoring.In this study,an intelligent IEQ monitoring and feedback system-the Intelligent Built Enviroment(IBEM)-is developed.Firstly,the IBEM hardware instrument integrates air temperature,relative humidity,CO_(2),particulate matter with an aerodynamic diameter no greater than _(2.5)μm(PM_(2.5)),and illuminance sensors within a small device.The accuracy of this integrated device was tested through a co-location experiment with reference sensors;the device exhibited a strong correlation with the reference sensors,with a slight deviation(R^(2)>0.97 and slopes between 1.01 and 1.05).Secondly,a wireless data transmission module,a cloud storage module,and graphical user interfaces(i.e.,a web platform and mobile interface)were built to establish a pathway for dataflow and interactive feedback with the occupants of the indoor environments.Thus,the IEQ parameters can be continuously monitored with a high spatiotemporal resolution,interactive feedback can be induced,and synchronous data collection on occupant satisfaction and objective environmental parameters can be realized.IBEM has been widely applied in 131 buildings in 18cities/areas in China,with 1188 sample locations.Among these applications,we report on the targeted IEQ diagnoses of two individual buildings and the exploration of relationships between subjective and objective IEQ data in detail here.This work demonstrates the great value of IBEM in both industrial and academic research.

关键词： Indoor environmental quality(IEQ) Sensors Continuous monitoring Graphical user interface Interactive feedback

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αExtractor: a system for automatic extraction of chemical information from biomedical literature

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Science China(Life Sciences) 2024年第3期67卷 618-621页

作者： Jiacheng Xiong Xiaohong Liu Zhaojun Li hongzhong Xiao Guangchao Wang Zhenjiang Niu Chaoyuan Fei Feisheng Zhong Gang Wang Wei Zhang Zunyun Fu Zhiguo Liu Kaixian chen Hualiang Jiang Mingyue Zheng Drug Discovery and Design Center State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China AI Department Suzhou Alphama Biotechnology Co.Ltd.Suzhou 215125China College of Computer and Information Engineering Dezhou UniversityDezhou 253023China

Dear Editor,Great progress has been made using artificial intelligence(AI) techniques in learning knowledge from biomedical databases in recent years, revolutionizing the study of many fields, such as protein structure prediction and protein design(Madani et al., 2023). However, there is massive biomedical knowledge not curated in the form of structured data but hidden in primary scientific literature.

关键词： has such knowledge

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Rapidly separating dissolving microneedles with sustained-release colchicine and stabilized uricase for simplified long-term gout management

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Acta Pharmaceutica Sinica B 2023年第8期13卷 3454-3470页

作者： Yao Yang Zimu Li Ping Huang Jiachan Lin Jinyuan Li Kexin Shi Jiahui Lin Jingwen Hu Zhuoxian Zhao Yongkang Yu hongzhong chen Xiaowei Zeng Lin Mei Institute of Pharmaceutics School of Pharmaceutical Sciences(Shenzhen)Sun Yat-sen UniversityShenzhen 518107China State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yatsen University Cancer CenterGuangzhou 510060China Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical SciencesPeking Union Medical CollegeTianjin300192China

Despite growing prevalence and incidence,the management of gout remains suboptimal.The intermittent nature of the gout makes the long-term urate-lowering therapy(ULT)particularly important for gout management.However,patients are reluctant to take medication day after day to manage incurable occasional gout flares,and suffer from possible long-term toxicity.Therefore,a safe and easy-tooperate drug delivery system with simple preparation for the long-term management of gout is very necessary.Here,a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal.This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention.Furthermore,its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models.Besides,the drug co-delivery system could help avoid long-term daily oral colchicine,a drug with a narrow therapeutic index.This system also avoids mass injection of uricase by improving its stability,enhancing the clinical application value of uricase.In general,this two-drug system reduces the dosage of uricase and colchicine and improves the patient’s compliance,which has a strong clinical translation.

关键词： Microneedles Colchicine Sustained-release Uricase Liposome Transdermal administration Gout management Long-term urate-lowering therapy

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计及电力不平衡风险的配电网分区协同规划

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电力自动化设备 2024年第7期44卷 86-93页

作者：李宏仲陈熙峰上海电力大学电气工程学院上海200090

在实现“双碳”目标的过程中,大量分布式可再生能源随机接入配电网。由于分布式电源出力的波动性,配电网可能出现弃电、切负荷等电力不平衡的情况。提出一种计及电力不平衡风险的配电网分区协同规划方法。构建一种基于非参数估计方法的... 详细信息

在实现“双碳”目标的过程中,大量分布式可再生能源随机接入配电网。由于分布式电源出力的波动性,配电网可能出现弃电、切负荷等电力不平衡的情况。提出一种计及电力不平衡风险的配电网分区协同规划方法。构建一种基于非参数估计方法的时序源荷特性仿射模型,以描述源荷特性的时序波动性和不确定性,并利用Wasserstein距离指标进行聚类,减少时序预测误差概率分布的数量;采用A*算法计算在电力廊道受限条件下负荷点之间的距离,并构建负荷点间距离矩阵和功率特性匹配度矩阵,以划分馈线区块;提出电力不平衡风险价值的计算方法,量化灵活性资源水平与电力不平衡风险间的关系;基于此,构建配电网双层协同规划模型,上层以线路和储能装置投资费用最低为目标,下层以配电网运行成本和电力不平衡风险成本最低为目标。以西北某地区实际配电网为案例,验证所提方法的有效性和优越性。

关键词：源荷特性馈线区块源网荷储不确定性配电网规划

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An efficient method of evaluating large scale urban residential skylight environment and an empirical study of Beijing main area

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Building Simulation 2021年第4期14卷 871-883页

作者： Taofang Yu hongzhong chen Ziwei Li Qiushi He Borong Lin Department of Urban Planning School of ArchitectureTsinghua UniversityBeijing100084China Department of Building Science School of ArchitectureTsinghua UniversityBeijing100084China College of Architecture&Urban Planning Beijing University of TechnologyBeijing100124China

A good skylight environment in urban residential areas is an important component of a healthy city,and has always been highly valued.With the rapid development of new-type urbanization,the density of buildings continues to increase,and megacities have entered the stage of stock transformation.An effective method for evaluating the skylight environment of large-scale urban residential areas is urgently needed.However,there is still a lack of empirical research methods and cases of large-scale residential skylight environment.In this regard,this article takes the megacity Beijing as the research object,and proposes an efficient analysis method of residential skylight environment that integrates multiple real-world data at city scale.In terms of data,it collects and integrates 3D data of urban-scale building space and residential boundary data;in terms of algorithm,Sky View Factor(SVF)is used as the evaluation index of residential skylight environment,and an efficient analysis method of urban-scale skylight environment based on cloud parallel simulation is realized.Through analysis,it is found that:(1)the average SVF value of Beijing residential area is 61%,which means that its skylight quality is in general level;(2)the skylight environment of Beijing residential area is distributed in a circle,and there are 4 types of skylight environment quality residential areas;(3)The skylight environment of Beijing residential area is relatively weakly related to the distance from the residential area to the city center and the average height of the residential buildings,and is closely related to the plot volume ratio,the residential building density and the shading from surrounding buildings.The highlight of this study lies in the empirical research on the skylight environment of mega-city residential areas that incorporates multiple real data for the first time,which can promote the study of skylight environment on a city scale and provide a reference for the updating of Beijing’s residential daylight environment.

关键词： urban skylight environment Sky View Factor Open Street Map Buildings Beijing residential areas

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A preference-based multi-objective building performance optimization method for early design stage

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Building Simulation 2021年第3期14卷 477-494页

作者： Borong Lin hongzhong chen Yanchen Liu Qiushi He Ziwei Li Department of Building Science Tsinghua UniversityBeijing 100084China College of Civil Engineering Guangzhou UniversityGuangzhou 510006China College of Architecture&Urban Planning Beijing University of TechnologyBeijing 100124China

A large number of cases show that the multi-objective optimization method can significantly improve building performance.The method for multi-objective building performance optimization(BPO)design has achieved rapid development in recent years.However,the BPO method still needs to be improved.Specifically,weak interaction between the optimization process and the decision-making process results in low optimization efficiency,which limits the widespread application of the optimization method in early design stage.In this paper,a new interactive BPO mode is explored to strengthen the interaction between the optimization process and decisionmaking process,and a preference-based multi-objective BPO method is proposed to account for designers'decision preferences during the optimization process,making the objective more controllable,improving the optimization efficiency and ensuring the diversity of solutions.Firstly,this paper illustrates the proposed method in detail,defines the concept of performance preference,expounds the flow of the preference-based multi-objective optimization algorithm,and proposes three indicators to evaluate the algorithm,which includes convergence speed,preference satisfaction rate,and diversity measurement.Secondly,through testing and comparison,it is found that the proposed preference-based algorithm has advantages over the non-preference optimization algorithm(represented by the NSGA-II algorithm).The proposed method leads to faster convergence and higher preference satisfaction,so it is more suitable for the BPO process in the early design stage.Specially,the proposed method can achieve 100%preference satisfaction rate with only 2400 simulations,while the non-preference method can only achieve 20%preference satisfaction rate after 5800 simulations.In this paper,a preference-based multi-objective BPO method is proposed to make the optimization process closely interact with the decision-making process and make the design preferences be accounted during the BPO process,thereby improving the

关键词： building performance optimization(BPO) preference oriented design Pareto-front early design stage

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