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Entrapping multifunctional dendritic nanoparticles into a hydrogel for local therapeutic delivery and synergetic immunochemotherapy

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Nano Research 2018年第11期11卷 6062-6073页

作者： Lei jiang Yang Ding Xialin Xue Sensen Zhou Cheng Li Xiaoke Zhang xiqun jiang State Key Laboratory of Natural Medicines Department of Pharmaceutics China Pharmaceutical University Nanjing 210009 China MOE Key Laboratory of High Performance Polymer Materials and Technology and Department of Polymer Science & EngineeringCollege of Chemistry & Chemical Engineering Nanjing University Nanjing 210093 China

Developing multifunctional nanoparticles to support new therapy models is a promising and challenging task to address the current dilemma on antitumor treatment. Herein, we incorporated multifunctional dendritic nanoparticles into a poly(D,L-lactide-co-glycolide)-poly(ethylene glycol)-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers thermosensitive injectable hydrogel matrix to construct a localized drug delivery system for combining chemotherapy and immunotherapy. The multifunctional dendritic nanoparticles were designed with following expectations: i, Dendritic scaffolds provide a hydrophobic interior to load the anticancer drug, doxorubicin (DOX), for chemotherapy; and ii, dendritic scaffolds are used to build arginine-rich molecules to provide the inducible nitric oxide synthase (iNOS) substrate, L-Arg, to M1 macrophages, which can produce the cytotoxic substance nitric oxide (NO) and subsequently induce tumor cell destruction through immunotherapy. It is noteworthy that the dendritic nanoparticles-in-hydrogel delivery system is able to gel at physiological temperature and serves as a warehouse for the sustained release of the drug. Ultimately, this system showed great efficacy in treating 4T1 cells-xenografted BALB/C mice (86.62% tumor growth inhibition). Therefore, this localized drug delivery system combining chemotherapy and immunotherapy provides a novel approach for cancer therapy.

关键词： multifunctional dendritic nanoparticles peptide dendrimer cancer therapy combined chemotherapy and immunotherapy

Emerging Designs of Aggregation-Induced Emission Agents for Enhanced Phototherapy Applications

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CCS Chemistry 2022年第2期4卷 401-419页

作者： Rui Qu Xu Zhen xiqun jiang MOE Key Laboratory of High Performance Polymer Materials and Technology Department of Polymer Science&EngineeringCollege of Chemistry&Chemical EngineeringNanjing UniversityNanjing 210093

Phototherapy,including photodynamic therapy(PDT)and photothermal therapy(PTT),that employs phototherapeutic agents to generate cytotoxic reactive oxygen species(ROS)or hyperthermia,is a promising approach for disease ***,conventional organic phototherapeutic agents suffer poor photostability and aggregation-caused quenching(ACQ)in the aggregate state,restricting their therapeutic ***-induced emission(AIE)agents can solve these issues with strong emission in the aggregate state and reverse designation to generate *** review summarizes the recent advances in the development of AIE phototherapy agents for enhanced PDT and PTT performances in biomedical ***,design strategies of AIE agents that adjust the intersystem crossing process or intramolecular charge transfer to boost ROS generation or regulate ROS types are *** AIE agents with ROS generation ability for biomedical applications including antitumor and antibacterial performances are then ***,designs and examples of AIE agents that enhance PTT performances through molecular motions are ***,the current challenges and perspectives of AIE agents in the phototherapy field are discussed.

关键词： aggregation-induced emission structural designing phototherapy photodynamic therapy photothermal therapy

Furan-modified thiadiazolo quinoxaline as an electron acceptor for constructing second near-infrared aggregation-induced emission fluorophores for beyond 1300 nm fluorescence/photoacoustic imaging and photothermal therapy

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Aggregate 2024年第2期5卷 345-356页

作者： Mengke Liang Luyu Liu Ying Sun Jia Li Ling’e Zhang xiqun jiang Wei Wu Department of Polymer Science&Engineering State Key Laboratory of Analytical Chemistry for Life ScienceCollege of Chemistry&Chemical EngineeringNanjing UniversityNanjingP.R.China

Creation of new fluorophores is important for understanding the structure-property relationship,by which the required optical properties are likely to be ***,through theory calculation,it is found that furan-modified thiadiazolo quinoxaline acting as an electron acceptor can endow donor-acceptor-donor(D-A-D)type second near-infrared(NIR-Ⅱ)fluorophores with longer emission wavelength than the other thiadiazolo quinoxaline-based acceptors containing pyridine,pyrrole,thiophene,and phenyl groups,*** the basis of this theoretical prediction,a D-A-D type NIR-Ⅱ fluorophore with 6,7-di(furan-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline(DFTQ)as the acceptor and dithieno[3,2-b:2′,3′-d]pyrrole(DTP)as the donor is designed and synthesized,and the aggregation-induced emission(AIE)function is further achieved by introducing the AIE units of tetraphenylethylene(TPE)and triphenylamine(TPA),respectively,totally forming three NIR-Ⅱ fluorophores DFTQ-DTP,DFTQ-DTPE,and *** biological applications,the fluorophores are encapsulated by amphiphilic DSPE-PEG2000 to generate water-dispersible nanoparticles(NPs).Almost the whole emission of each of the NPs falls into the NIR-Ⅱ spectral range,with part emission beyond 1300 *** using DFTQ-DTPA NPs as the contrast and photothermal therapy(PTT)agent,high-resolution in vivo fluorescence imaging is achieved in the greater than 1300 nm window,and their good performance in photoacoustic imaging and high tumor PTT efficacy in tumor-bearing mice are also *** together,this work mainly provides a strong electron acceptor for constructing longemitting fluorophores,and by using the electron acceptor,a AIE fluorophore with desirable quantum yield(QY)and photothermal conversion efficienciy(PCE)is synthesized and demonstrated to be promising in fluorescence/photoacoustic imaging and PTT.

关键词： aggregation-induced emission fluorescence imaging photoacoustic imaging photothermal therapy second near-infrared fluorophores

Synthesis of novel gelatin/poly(acrylic acid) nanorods via the self-assembly of nanospheres

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Science China Chemistry 2011年第2期54卷 392-396页

作者： DING Dan WANG Jing CHEN Ying WU Wei jiang xiqun Laboratory of Mesoscopic Chemistry and Department of Polymer Science & Engineering College of Chemistry & Chemical Engineering Nanjing University Nanjing 210093 China

In this work, gelatin-poly（acrylic acid）（GEL-PAA） nanospheres with diameter of around 35 nm were prepared using a polymermonomer （gelatin-AA） pair reaction system. These nanospheres can self-assemble into nanorods in aqueous solution at 4 ℃. Based on the observation that the intermediate state of the formation of the nanorods and the facts that the self-assembly can only occur at relatively low temperature and the gelatin molecules on the outermost layer of the GEL-PAA nanospheres can be renatured to triple helix conformation, it can be rationally inferred that the hydrogen bonding and electrostatic interactions between the gelatin molecules with the triple helix structure induce the one-dimensional self-assembly of the nanospheres into nanorods.

关键词： gelatin nanorods triple helical conformation one-dimensional self-assembly

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Preparation of porous chitosan-poly(acrylic acid)-calcium phosphate hybrid nanoparticles via mineralization

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Chinese Science Bulletin 2009年第10期54卷 3127-3136页

作者： CHEN ChangJing DENG Yu YAN ErYun HU Yong jiang xiqun Nanjing National Laboratory of Microstructures Department of Material Science and Engineering Nanjing University Nanjing 210093 China Laboratory of Mesoscopic Chemistry and Department of Polymer Science & Engineering College of Chemistry & Chemical Engi- neering Nanjing University Nanjing 210093 China Center for Materials Analysis Nanjing University Nanjing 210093 China

In this work, the preparation of chitosan-poly(acrylic acid)-calcium phosphate hybrid nanoparticles (CS-PAA-CaP NP) based on the mineralization of calcium phosphate (CaP) on the surface of chito-san-poly (acrylic acid) nanoparticles (CS-PAA NPs) was reported. CS-PAA-CaP NPs were achieved by directly adding ammonia to the aqueous solution of CS-PAA nanoparticles or by thermal decomposi-tion of urea in the aqueous solution of CS-PAA nanoparticles, resulting in the mineralization of CaP on the surface of CS-PAA NPs. Through these two routes, especially using urea as a pH-regulator, the precipitation of CS-PAA NPs, a common occurrence in basic environment, was avoided. The size, morphology and ingredient of CS-PAA-CaP hybrid nanoparticles were characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), scanning electron microscope (SEM), thermogravimetry analysis (TGA) and X-ray diffractometer (XRD). When urea was used as the pH regulator to facilitate the mineralization during the thermal urea decomposition procedure, regular CS-PAA-CaP hybrid nanoparticles with a porosity-structural CaP shells and 400―600 nm size were obtained. TGA result revealed that the hybrid NPs contained approximately 23% inorganic component, which was consistent with the ratio of starting materials. The XRD spectra of hybrid nanoparticles in-dicated that dicalcium phosphate (DCP: CaHPO4) crystal was a dominant component of mineralization. The porous structure of the CS-PAA-CaP hybrid NPs might be greatly useful in pharmaceutical and other medical applications.

关键词：纳米粒子丙烯酸壳聚糖磷酸钙多孔制备混合矿化

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Dendrimer-based nanoparticles in cancer chemotherapy and gene therapy

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Science China Materials 2018年第11期61卷 1404-1419页

作者： Lei jiang Sensen Zhou Xiaoke Zhang Wei Wu xiqun jiang MOE Key Laboratory of High Performance Polymer Materials and Technology and Department of Polymer Science ＆ EngineeringCollege of Chemistry ＆ Chemical EngineeringNanjing UniversityNanjing 210093China State Key Laboratory of Natural Medicines Department of PharmaceuticsChina Pharmaceutical UniversityNanjing 210009China

This review discusses recent studies on dendrimer-based nanoparticles in cancer chemotherapy and gene therapy. In order to achieve the high efficacy and low side effects of chemotherapy and gene therapy, it is essential to combine the unique features of dendrimers and the specific tumor microenvironment to target delivery and control release of therapeutic agents to tumor tissues and cells. Strategies to design the dendrimer-based delivery system in this review include non-modified dendrimers, dendrimer conjugates, assembled amphiphilic dendrimers, nanohybrid dendrimer carriers and dendrimers with inherent activity. In addition, specific functional groups on these dendrimers as stimuli-responsive system for targeting delivery and controlled release of therapeutic agents are discussed.

关键词： dendrimer-based nanoparticles cancer chemotherapy gene therapy

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乏氧光学影像探针的设计与应用

高等学校化学学报 2022年第12期43卷 185-196页

作者：李成周森森蒋锡群南京大学化学化工学院高分子科学与工程系江苏省纳米技术重点实验室南京210023

氧气在生命活动中具有重要意义,为需氧生物提供了重要的能量来源,氧气供应不足会导致组织乏氧.乏氧往往与炎症、慢性伤口及肿瘤等多种疾病密切相关,而组织氧浓度是评估机体健康的重要依据.光学成像在空间分辨率、灵敏性和成本方面的巨... 详细信息

氧气在生命活动中具有重要意义,为需氧生物提供了重要的能量来源,氧气供应不足会导致组织乏氧.乏氧往往与炎症、慢性伤口及肿瘤等多种疾病密切相关,而组织氧浓度是评估机体健康的重要依据.光学成像在空间分辨率、灵敏性和成本方面的巨大优势使其成为炎症、癌症、脑部疾病和手术导航的重要影像诊断工具.本文介绍了数种乏氧响应的光学探针的合成策略,并展示了不同的乏氧光学探针在肿瘤检测、炎症监测、伤口氧含量监测、治疗响应监测和食品包装检测等方面的应用,最后探讨了乏氧光学成像的应用前景.

关键词：乏氧磷光探针荧光探针

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高分子钆配合物磁共振造影剂的研究进展

离子交换与吸附 2010年第3期26卷 280-288页

作者：谢晨郭舰武伟蒋锡群南京大学化学化工学院

近年来,高分子磁共振造影剂因其弛豫效率高、体内驻留时间长、器官选择性好和毒副作用小等优点而倍受关注。本文综述用于磁共振造影剂的高分子钆配合物的最新研究进展。讨论了将官能化的配合物与线性、树状聚合物及生物大分子结合制备... 详细信息

近年来,高分子磁共振造影剂因其弛豫效率高、体内驻留时间长、器官选择性好和毒副作用小等优点而倍受关注。本文综述用于磁共振造影剂的高分子钆配合物的最新研究进展。讨论了将官能化的配合物与线性、树状聚合物及生物大分子结合制备高分子钆配合物的合成方法,并介绍了高分子钆配合物磁共振造影剂的性能、应用和发展前景。

关键词：磁共振造影剂钆配合物弛豫性能

Precise nanomedicine for intelligent therapy of cancer

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Science China Chemistry 2018年第12期61卷 1503-1552页

作者： Huabing Chen Zhanjun Gu Hongwei An Chunying Chen Jie Chen Ran Cui Siqin Chen Weihai Chen Xuesi Chen Xiaoyuan Chen Zhuo Chen Baoquan Ding Qian Dong Qin Fan Ting Fu Dayong Hou Qiao jiang Hengte Ke xiqun jiang Gang Liu Suping Li Tianyu Li Zhuang Liu Guangjun Nie Muhammad Ovais Daiwen Pang Nasha Qiu Youqing Shen Huayu Tian Chao Wang Hao Wang Ziqi Wang Huaping Xu jiang-Fei Xu Xiangliang Yang Shuang Zhu Xianchuang Zheng Xianzheng Zhang Yanbing Zhao Weihong Tan Xi Zhang Yuliang Zhao State Key Laboratoiy of Radiation Medicine and Protection Jiangsu Key Laboratoiy of Neuropsychiatric Diseases College of Pharmaceutical Sciences Soochow University Suzhou 215123 China Key Laboratoiy of Biomedical Polymers of Ministry of Education Department of Chemistiy Wuhan University Wuhan 430072 China Laboratoiy of Molecular Imaging and Nanomedicine National Institute of Biomedical Imaging and Bioengineering National Institutes of Health Bethesda MD 20892 USA Molecular Science and Biomedicine Laboratoiy State Key Laboratory of Chemo/Bio-Sensing and Chemometrics College of Chemistiy and Chemical Engineering Aptamer Engineering Center of Hunan Province Hunan University Changsha 410082 China jiangsu Key Laboratoiy for Carbon-Based Functional Materials & Devices Institute of Functional Nano & Soft Materials Soochow University Suzhou 215123 China Department of Polymer Science and Engineering College cf Chemistry and Chemical Engineering Nanjing University Nanjing 210093 China State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine School of Public Health Xiamen University Xiamen 361102 China Department of Chemistiy Tsinghua University Beijing 100084 China National Engineering Research Center for Nanomedicine College of Life Science and Technology Huazhong University of Science and Technology Wuhan 430074 China Department of Chemistiy and Department of Physiology and Functional Genomics Center for Research at Bio/nano Interface Health Cancer Center UF Genetics Institute and McKnight Brain Institute University of Florida Gainesville FL 32611-7200 USA institute of High Energy Physics Chinese Academy of Sciences Beijing 100049 China CAS Key Laboratoiy for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 China University of Chinese Academy of Sciences Beijing 100049 China Key Labo

Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.

关键词： nanomedicine nanoparticles cancer therapy cancer imaging intelligent therapy