硼替佐米的高乙二醇纳米果剂的轻松策略，具有提高的稳定性，增强的生物相容性，pH对照的拆卸和释放
A Facile Strategy for PEGylated Nanoprodrug of Bortezomib with Improved Stability, Enhanced Biocompatibility, pH-Controlled Disassembly, and Release
影响因子:4.10000
分区:医学4区 / 高分子科学3区 生化与分子生物学4区 材料科学：生物材料4区
发表日期:2025 Feb
作者:
Naikuan Fu, Yinan Zeng, Jing Zhang, Peng Zhang, Hong Zhang, Shicheng Yang, Jianhua Zhang
摘要
硼替佐米（BTZ）的治疗功效通常由于溶解度较低，体内稳定性较差和非特异性毒性而受到限制。 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.详细研究了MPEG-CA-CA-BTZ纳米颗粒的结构和形态，物理化学特征，药物载荷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条件下自我组装成具有均匀尺寸和稳定分散的纳米结构（pH 7.4）（pH 7.4），而且还对肿瘤酸微环境做出反应，并实现pH传导的BTZ，并通过酸触发的btz释放，从而通过mmpeg-ca-btply的ca键触发了酸触发的裂解，从而释放了Mpeg-ca-btbly的裂解。纳米颗粒。预计MPEG-CA-BTZ纳米颗粒具有巨大的潜力，作为BTZ药物制剂的有希望的纳米植物，以提高治疗功效并降低BTZ的副作用。考虑到易于获得且具有生物相容性的赋形剂和简单的制备过程，此处设计的策略提供了一种简便而有希望的方法，可以协同将Pegylation和PH-敏感性的功能整合到含硼酸的小分子药物药物中。
Abstract
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.