{"title":"基于共价键的动态纳米平台,用于细胞内协同输送蛋白质药物和化疗药物,增强抗癌效果","authors":"Sai-Nan Liu, Jia-Hui Meng, Li-Yun Cui, Hua Chen, Lin-Qi Shi, Ru-Jiang Ma","doi":"10.1007/s10118-024-3090-z","DOIUrl":null,"url":null,"abstract":"<p>Efficient intracellular delivery of protein drugs is critical for protein therapy. The combination of protein drugs with chemotherapeutics represents a promising strategy in enhancing anti-cancer effect. However, co-delivery systems for efficient delivery of these two kinds of drugs are still lacking because of their different properties. Herein, we show a well-designed delivery system based on dynamic covalent bond for efficient intracellular co-delivery of ribonuclease A (RNase A) and doxorubicin (DOX). Two polymers, PEG-<i>b</i>-P(Asp-<i>co</i>-AspDA) and PAE-<i>b</i>-P(Asp-<i>co</i>-AspPBA), and two 2-acetylphenylboronic acid (2-APBA)-functionalized drugs, 2-APBA-RNase A and 2-APBA-DOX, self-assemble into mixed-shell nanoparticles (RNase A/DOX@MNPs) <i>via</i> dynamic phenylboronic acid (PBA)-catechol bond between PBA and dopamine (DA) moieties. The PBA-catechol bond endows the nanoparticles with high stability and excellent stimulus-responsive drug release behavior. Under the slight acidic environment at tumor tissue, RNase A/DOX@MNPs are positively charged, promoting their endocytosis. Upon cellular uptake into endosome, further protonation of PAE chains leads to the rupture of endosomes because of the proton sponge effect and the cleavage of PBA-catechol bond promotes the release of two drugs. In cytoplasm, the high level of GSH removed the modification of 2-APBA on drugs. The restored RNase A and DOX show a synergistic and enhanced antic-cancer effect. This system may be a promising platform for intracellular co-delivery of protein drugs and chemotherapeutics.</p>","PeriodicalId":517,"journal":{"name":"Chinese Journal of Polymer Science","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Dynamic Covalent Bonding-based Nanoplatform for Intracellular Co-Delivery of Protein Drugs and Chemotherapeutics with Enhanced Anti-Cancer Effect\",\"authors\":\"Sai-Nan Liu, Jia-Hui Meng, Li-Yun Cui, Hua Chen, Lin-Qi Shi, Ru-Jiang Ma\",\"doi\":\"10.1007/s10118-024-3090-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Efficient intracellular delivery of protein drugs is critical for protein therapy. The combination of protein drugs with chemotherapeutics represents a promising strategy in enhancing anti-cancer effect. However, co-delivery systems for efficient delivery of these two kinds of drugs are still lacking because of their different properties. Herein, we show a well-designed delivery system based on dynamic covalent bond for efficient intracellular co-delivery of ribonuclease A (RNase A) and doxorubicin (DOX). Two polymers, PEG-<i>b</i>-P(Asp-<i>co</i>-AspDA) and PAE-<i>b</i>-P(Asp-<i>co</i>-AspPBA), and two 2-acetylphenylboronic acid (2-APBA)-functionalized drugs, 2-APBA-RNase A and 2-APBA-DOX, self-assemble into mixed-shell nanoparticles (RNase A/DOX@MNPs) <i>via</i> dynamic phenylboronic acid (PBA)-catechol bond between PBA and dopamine (DA) moieties. The PBA-catechol bond endows the nanoparticles with high stability and excellent stimulus-responsive drug release behavior. Under the slight acidic environment at tumor tissue, RNase A/DOX@MNPs are positively charged, promoting their endocytosis. Upon cellular uptake into endosome, further protonation of PAE chains leads to the rupture of endosomes because of the proton sponge effect and the cleavage of PBA-catechol bond promotes the release of two drugs. In cytoplasm, the high level of GSH removed the modification of 2-APBA on drugs. The restored RNase A and DOX show a synergistic and enhanced antic-cancer effect. This system may be a promising platform for intracellular co-delivery of protein drugs and chemotherapeutics.</p>\",\"PeriodicalId\":517,\"journal\":{\"name\":\"Chinese Journal of Polymer Science\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2024-02-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chinese Journal of Polymer Science\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1007/s10118-024-3090-z\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"POLYMER SCIENCE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Journal of Polymer Science","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s10118-024-3090-z","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"POLYMER SCIENCE","Score":null,"Total":0}
A Dynamic Covalent Bonding-based Nanoplatform for Intracellular Co-Delivery of Protein Drugs and Chemotherapeutics with Enhanced Anti-Cancer Effect
Efficient intracellular delivery of protein drugs is critical for protein therapy. The combination of protein drugs with chemotherapeutics represents a promising strategy in enhancing anti-cancer effect. However, co-delivery systems for efficient delivery of these two kinds of drugs are still lacking because of their different properties. Herein, we show a well-designed delivery system based on dynamic covalent bond for efficient intracellular co-delivery of ribonuclease A (RNase A) and doxorubicin (DOX). Two polymers, PEG-b-P(Asp-co-AspDA) and PAE-b-P(Asp-co-AspPBA), and two 2-acetylphenylboronic acid (2-APBA)-functionalized drugs, 2-APBA-RNase A and 2-APBA-DOX, self-assemble into mixed-shell nanoparticles (RNase A/DOX@MNPs) via dynamic phenylboronic acid (PBA)-catechol bond between PBA and dopamine (DA) moieties. The PBA-catechol bond endows the nanoparticles with high stability and excellent stimulus-responsive drug release behavior. Under the slight acidic environment at tumor tissue, RNase A/DOX@MNPs are positively charged, promoting their endocytosis. Upon cellular uptake into endosome, further protonation of PAE chains leads to the rupture of endosomes because of the proton sponge effect and the cleavage of PBA-catechol bond promotes the release of two drugs. In cytoplasm, the high level of GSH removed the modification of 2-APBA on drugs. The restored RNase A and DOX show a synergistic and enhanced antic-cancer effect. This system may be a promising platform for intracellular co-delivery of protein drugs and chemotherapeutics.
期刊介绍:
Chinese Journal of Polymer Science (CJPS) is a monthly journal published in English and sponsored by the Chinese Chemical Society and the Institute of Chemistry, Chinese Academy of Sciences. CJPS is edited by a distinguished Editorial Board headed by Professor Qi-Feng Zhou and supported by an International Advisory Board in which many famous active polymer scientists all over the world are included. The journal was first published in 1983 under the title Polymer Communications and has the current name since 1985.
CJPS is a peer-reviewed journal dedicated to the timely publication of original research ideas and results in the field of polymer science. The issues may carry regular papers, rapid communications and notes as well as feature articles. As a leading polymer journal in China published in English, CJPS reflects the new achievements obtained in various laboratories of China, CJPS also includes papers submitted by scientists of different countries and regions outside of China, reflecting the international nature of the journal.