南开大学马如江团队报道了一种基于动态共价键的纳米平台，用于细胞内共递送具有增强抗癌作用的蛋白质药物和化疗药物。相关研究成果于2024年2月29日发表于国际一流学术期刊《中国高分子科学杂志》。

蛋白质药物细胞内高效递送对于蛋白质治疗至关重要。蛋白质药物与化学治疗药物的结合是提高抗癌效果的一种很有前途的策略。然而，由于这两种药物的不同性质，用于有效递送它们的共递送系统仍然缺乏。

该文中，研究人员展示了一种基于动态共价键的精心设计的递送系统，用于核糖核酸酶a（RNase a）和阿霉素（DOX）的有效细胞内共递送。两种聚合物，PEG-b-P（Asp-co-AspDA）和PAE-b-P（Asp-co-AspPBA），以及两种2-乙酰基苯基硼酸（2-APBA）功能化药物，2-APBA-RNase A和2-APBA-DOX，通过PBA和多巴胺（DA）部分之间的动态苯基硼酸（PBA）-邻苯二酚键自组装成混合壳纳米颗粒（RNase A/DOX@MNPs)。

PBA-邻苯二酚键赋予纳米颗粒高稳定性和优异的刺激响应性药物释放行为。在肿瘤组织的微酸性环境下，RNase A/DOX@MNPs带正电荷，促进其内吞作用。在细胞摄取到内体中时，由于质子海绵效应，PAE链的进一步质子化导致内体破裂，并且PBA-邻苯二酚键的断裂促进了两种药物的释放。在细胞质中，高水平的GSH去除了2-APBA对药物的修饰。恢复的RNase A和DOX显示出协同作用和增强的抗癌作用。

该系统可能是蛋白质药物和化疗药物的细胞内共递送的一个有前途的平台。

附：英文原文

Title: A Dynamic Covalent Bonding-based Nanoplatform for Intracellular Co-Delivery of Protein Drugs and Chemotherapeutics with Enhanced Anti-Cancer Effect

Author: Sai-Nan Liu, Jia-Hui Meng, Li-Yun Cui, Hua Chen, Lin-Qi Shi, Ru-Jiang Ma

Issue&Volume: 2024-02-29

Abstract: 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.

DOI: 10.1007/s10118-024-3090-z

Source: https://www.cjps.org/en/article/doi/10.1007/s10118-024-3090-z/