Tailoring pH-ultra-sensitive oncolytic polyesters via a manageable polymer blending strategyOA
pH-ultra-sensitive oncolytic polymers hold great promise for cancer therapy due to their selective oncolytic activity in the tumor microenvironment.However,achieving well-defined structures and finely tunable pH responsiveness for these polymers remains a challenge.Herein,we developed a straightforward blending strategy using two welldefined alternating polyesters with distinct pH sensitivities to create pH-ultra-sensitive hybrid polyester nanoparticles(Hps)with precisely engineered responsiveness.By varying the mass ratio of the two components,the pK_(a)of the Hps could be continuously tuned from 6.37 to 7.04.The resulting Hps demonstrated a sharp pH-dependent membranolytic activity switch within a 0.3 pH unit window,with minimal cytotoxicity observed at pH values above the transition pH.A lead Hp formulation identified through screening exhibited potent cytotoxicity at pH 6.8,along with a favorable safety profile and significant antitumor efficacy in vivo.This blending strategy establishes a flexible and simple platform for customizing pH responsiveness of oncolytic polymers,advancing oncolytic therapy.
Chanjuan Su;Yuxuan Zeng;Shihua Zhang;Yueling Yuan;Yuxuan Gong;Huosheng Zhou;Fuxiang Wang;Jihong Wang;Menghua Xiong;Yan Bao
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Guangdong-Hong Kong Joint Laboratory for RNA Medicine,Medical Research Center,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,ChinaSchool of Biomedical Sciences and Engineering,South China University of Technology,Guangzhou International Campus,Guangzhou 511442,China National Engineering Research Center for Tissue Restoration and Reconstruction,South China University of Technology,Guangzhou 510006,China Guangdong Province Key Laboratory of Biomedical Engineering,South China University of Technology,Guangzhou 510006,China Key Laboratory of Biomedical Materials of the Ministry of Education,South China University of Technology,Guangzhou 510006,ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Guangdong-Hong Kong Joint Laboratory for RNA Medicine,Medical Research Center,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Guangdong-Hong Kong Joint Laboratory for RNA Medicine,Medical Research Center,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,China Guangdong Provincial Key Laboratory of Cancer Pathogenesis and Precision Diagnosis and Treatment,Shenshan Medical Center,Sun Yatsen Memorial Hospital,Sun Yat-sen University,Shanwei 516621,ChinaSchool of Biomedical Sciences and Engineering,South China University of Technology,Guangzhou International Campus,Guangzhou 511442,China National Engineering Research Center for Tissue Restoration and Reconstruction,South China University of Technology,Guangzhou 510006,China Guangdong Province Key Laboratory of Biomedical Engineering,South China University of Technology,Guangzhou 510006,China Key Laboratory of Biomedical Materials of the Ministry of Education,South China University of Technology,Guangzhou 510006,ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Guangdong-Hong Kong Joint Laboratory for RNA Medicine,Medical Research Center,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Guangdong-Hong Kong Joint Laboratory for RNA Medicine,Medical Research Center,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,ChinaSchool of Biomedical Sciences and Engineering,South China University of Technology,Guangzhou International Campus,Guangzhou 511442,China National Engineering Research Center for Tissue Restoration and Reconstruction,South China University of Technology,Guangzhou 510006,China Guangdong Province Key Laboratory of Biomedical Engineering,South China University of Technology,Guangzhou 510006,China Key Laboratory of Biomedical Materials of the Ministry of Education,South China University of Technology,Guangzhou 510006,ChinaSchool of Biomedical Sciences and Engineering,South China University of Technology,Guangzhou International Campus,Guangzhou 511442,China National Engineering Research Center for Tissue Restoration and Reconstruction,South China University of Technology,Guangzhou 510006,China Guangdong Province Key Laboratory of Biomedical Engineering,South China University of Technology,Guangzhou 510006,China Key Laboratory of Biomedical Materials of the Ministry of Education,South China University of Technology,Guangzhou 510006,ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Guangdong-Hong Kong Joint Laboratory for RNA Medicine,Medical Research Center,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou 510120,China
医药卫生
pH-ultra-sensitive polymeroncolytic polymerpH responsivenesscancer therapy
《Nano Research》 2026 (3)
P.685-692,8
supported by the National Natural Science Foundation of China(Nos.32522050,32371389,and 52273127)Guangdong Basic and Applied Basic Research Foundation(Nos.2023B1515020086,and 2023A1515111158)Guangdong Science and Technology Department(No.2024B1212030002)Guangdong Provincial Medical Research Fund(No.B2025269).
评论