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Modulation of Conformational Transition of Polypeptides under Slightly Acidic Environment

Chinese Journal of Chemistry 2022年第24期40卷 2981-2987,I0002页

作者： Jie Li Jiajie Zhang Qi Long Weisheng Guo Menghua Xiong Guangzhou First People's Hospital School of Biomedical Sciences and EngineeringSouth China University of TechnologyGuangzhou International CampusGuangzhouGuangdong511442 China National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhouGuangdong510006 China Translational Medicine Center Key Laboratory of Molecular TargetClinical PharmacologySchool of Pharmaceutical SciencesThe Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdong510260 China Key Laboratory of Biomedical Engineering of Guangdong Province and Innovation Center for Tissue Restoration and ReconstructionSouth China University of TechnologyGuangzhouGuangdong510006 China Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education South China University of TechnologyGuangzhouGuangdong510006 China

Controlling the conformational transition of polypeptides under slightly acidic environment is challenging.Herein,we report a class of ph-responsive helix-to-coil conformationally transitionable polypeptides(pCTPs)by simply conjugating tertiary amine groups(TAs)to polylysine.Their conformation is highly dependent on the charge state of TAs,showing a helical structure when most TAs are deprotonated and a non-helical structure when majority of TAs are protonated.The conformational transition ph can be modulated by tuning the hydrophobicity of TAs and the incorporation of hydrophobic monomers at a ph range of 7.2 to 6.0.Such pCTP showed a vesicle-to-micelle transition when their conformation transformed from helix to coil,facilitating controlled drug release.Our study provided an approach to control the conformational transition of polypeptides under slightly acidic condition.

关键词： Peptides Conformational transition Helical structures pH responsiveness Drug delivery

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Switchable nanoparticles complexing cisplatin for circumventing glutathione depletion in breast cancer chemotherapy

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Chinese Chemical Letters 2023年第5期34卷 414-419页

作者： Ming Chen Ying Xie Qian Luo Jiarui Xu Yuxin Ren Rui Liu Huihui Zhao Yuling Chen Hexuan Feng Yafei Du Jianwei Li Guiling Wang Wanliang Lu State Key Laboratory of Natural and Biomimetic Drugs Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systemsand School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Cisplatin is broad-spectrum chemotherapeutic agent that has been widely used for the treatment of a variety of malignant tumors including breast cancer.However,the cisplatin chemoresistance,which derives from the inactivation by glutathione(GSH)depletion,remains a scientific issue to solve.Here,we report a novel type of smart disulfide switchable nanoparticles complexing cisplatin(switch NPs-cisplatin)that is rationally designed,and engineered by synthesizing a hyaluronic acid disulfide bonded polyaspartic acid(HA-ss-Pasp)and complexing cisplatin.The results showed that the switch NPs-cisplatin had a nanoscale of particle size(150 nm),higher drug encapsulation efficiency(>90%),and suitable drug release profile.They demonstrated evident pH responsiveness and GSH responsiveness,and targeting effect in the resistant breast cancer cells.Furthermore,they were able to block the cisplatin depletion by GSH in the resistant cancer cells,thereby circumventing the chemoresistance.Consequently,switch NPs-cisplatin displayed a remarkable killing effect in the resistant breast cancer cells in vitro,and in the resistant breast cancer-bearing mice.In conclusion,switch NPs-cisplatin could be used as a smart formulation of cisplatin for overcoming the chemoresistance of breast cancer.The present study also offers a universal drug delivery carrier platform for highly efficient but low systemic toxic chemotherapy.

关键词： Disulfide switchable nanoparticles pH responsiveness GSH depletion Cisplatin chemoresistance Breast cancer

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