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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

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Fluorescent Organohydrogel with Thermal-Induced Color Change for Anti-counterfeiting

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Chinese Journal of Chemistry 2022年第3期40卷 337-342页

作者： Xiaoxia Le Hui Shang Shirong Gu Guangqiang Yin Fuqing Shan Danyang Li Tao Chen 无 Key Laboratory of Marine Materials and Related Technologies Zhejiang Key Laboratory of Marine Materials and Protective TechnologiesNingbo Institute of Material Technology and EngineeringChinese Academy of SciencesNingboZhejiang 315201China School of Chemical Sciences University of Chinese Academy of SciencesBeijing 100049China Department of Orthopedics Lihuili Hospital of Ningbo Medical CenterNingboZhejiang 315048China

Smart fluorescent patterns enable dynamic color variation under external stimuli,showing a much higher security level in the field of anti-counterfeiting.However,there is still lacking of a simple and convenient way to achieve dynamic fluorescence changes.Herein,a fluorescent organohydrogel made up of a poly(N,/N-dimethylacrylamide-co-isopropylacrylamide)(p(DMA-NIPAM))hydrogel network and a polyflauryl methacrylate)(PLMA)organogel network was fabricated via a two-step interpenetrating technique.The former network bears naphthalimide moieties(DEAN,green fluorescent monomer)and the later contains 6-acrylamidopicolinic acid(6APA,fluorescent ligand),leading to emitting green fluorescence.When Eu^(3+) was introduced and coordinated with 6APA,the organohydrogel displays red fluorescence,which can further emit yellow after applying thermal stimulus.Furthermore,by adjusting the proportion of comonomers,various organohydrogels can be obtained,which can be programmed and act as an effective platform for the encryption and decryption of secret information.

关键词： Dyes/pigments Fluorescence Gels Information encryption stimuli responsiveness

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Ultra-stable and multistimuli-responsive nanoparticles coated with zwitterionic pillar[n]arene for enhanced cellular uptake

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Chinese Chemical Letters 2021年第3期32卷 1025-1028页

作者： Yupeng Jiao Shang Lan Da Ma Department of Chemistry Fudan UniversityShanghai 200433China

Nanoparticle surface property is crucial for circulation stability,cellullar uptake and other biological characteristics.Zwitte rionic pillar[n]arenes(ZPns)we re used to coat gold nanopa rticles(GNPs)via hostguest interaction.The resulting GNPs demonstrated higher stability in blood serum compared to polyethylene glycol(PEG)-coated GNPs.ZPn-coated GNPs were responsive to UV-irradiation,competitive displacement and acidic pH.UV-irradiation or competitive displacement could lead to the removal of ZPn coating to expose GNPs,which enhanced cell uptake efficiency by 5.9-and 7.4-fold,respectively.

关键词： Host-guest systems stimuli responsiveness Zwitterionic ligands Gold nanoparticles Cellular uptake

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