硼替佐米（BTZ）由于溶解度低、体内稳定性差和非特异性毒性，其治疗效果往往受到限制。在此，首先合成了一种儿茶酚功能化的聚乙二醇（mPEG-CA），然后通过形成动态硼酸酯键，很容易地使用mPEG-CA与BTZ缀合，得到聚乙二醇化的BTZ前药（mPEG-CA-BTZ） pH控制分解和药物释放的能力。详细研究了 mPEG-CA-BTZ 纳米颗粒的结构和形态、理化特性、载药量和释放以及体外细胞毒性。结果表明，mPEG-CA-BTZ不仅可以在生理pH条件（pH 7.4）下自组装成尺寸均匀、分散稳定的纳米结构，而且可以响应肿瘤酸性微环境，通过酸触发实现pH控制的BTZ释放硼酸酯键的断裂，mPEG-CA-BTZ 的分解，从而分解 mPEG-CA-BTZ 纳米颗粒。 mPEG-CA-BTZ 纳米颗粒有望作为 BTZ 药物制剂的有前途的纳米平台具有巨大潜力，以提高治疗效果并减少 BTZ 的副作用。考虑到容易获得且生物相容的赋形剂和简单的制备过程，本文设计的策略提供了一种简便且有前景的方法，将聚乙二醇化和 pH 敏感性的功能协同整合到含硼酸的小分子药物中。© 2024 Wiley‐VCH GmbH。

The therapeutic efficacy of bortezomib (BTZ) is often limited due to low solubility, poor stability in vivo and nonspecific toxicity. Herein, a kind of catechol-functionalized polyethylene glycol (mPEG-CA) is first synthesized and then mPEG-CA is readily used to conjugate with BTZ by the formation of dynamic boronate bonds to obtain PEGlyated BTZ prodrug (mPEG-CA-BTZ) with the ability of pH-controlled disassembly and drug release. The structure and morphology, physicochemical characteristics, drug loading, and release as well as in vitro cytotoxicity of mPEG-CA-BTZ nanoparticles are investigated in detail. The results demonstrated that mPEG-CA-BTZ can not only self-assemble into nanostructures with uniform size and stable dispersion in physiological pH condition (pH 7.4) but also respond to the tumor acid microenvironment and achieve pH-controlled BTZ release by acid-triggered cleavage of boronate bonds, decomposition of mPEG-CA-BTZ and thus disassembly of mPEG-CA-BTZ nanoparticles. mPEG-CA-BTZ nanoparticles are expected to have great potential as a promising nanoplatform for pharmaceutical formulations of BTZ to increase therapeutic efficacy and decrease side effects of BTZ. Considering the easily available and biocompatible excipients and simple preparation process, the strategy designed herein provides a facile and promising approach to synergistically integrate the function of PEGylation and pH-sensitiveness into boronic acid-containing small molecule pharmaceutical agents.© 2024 Wiley‐VCH GmbH.