Dual character of surface engineering on SN38 prodrug nano-assemblies: divergent effects on in vitro and in vivo behavior

作者：Yinyin Li, Zhi-Yu Kuang, Baoyuan Zhang, Yanzhong Hao, Lingxiao Li, Jingxuan Zhang, Ya-Fan Xiao, Bowen Zhang, Xianbao Shi, Xiaohui Pu, Zhonggui He, Bingjun Sun · 发表于：Military Medical Research · 年份：2025 · DOI：10.1186/s40779-025-00648-6 · 被引用次数：2 · 研究领域：Nanoparticle-Based Drug Delivery、Nanoplatforms for cancer theranostics、Graphene and Nanomaterials Applications

BACKGROUND: Surface engineering has emerged as a promising strategy to enhance the performance of nanomedicines. In particular, the PEGylation levels for chemotherapy drug 7-Ethyl-10-hydroxycamptothecin (SN38) prodrug nanoparticles (NPs) play a crucial role in determining their stability, drug release kinetics, cytotoxicity, cellular uptake, in vivo pharmacokinetics, biodistribution, and antitumor efficacy. The study aims to investigate the surface engineering for chemotherapy drugs, providing new solutions for improving their in vivo delivery. METHODS: ; 0%, 5%, 20%, 40%, 60%, 80%, 100%, 150%, and 200% NPs) incorporated on SN38 prodrug NPs via surface engineering. Drug release was measured using high-performance liquid chromatography (HPLC), while cytotoxicity was assessed via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular uptake was accurately quantified using liquid chromatography-mass spectrometry (LC-MS). The in vivo pharmacokinetics of the NPs were evaluated in Sprague-Dawley rats, and the biodistribution and antitumor efficacy were assessed using a CT26 colon tumor-bearing BALB/c mice model. Additionally, we examined intestinal toxicity to evaluate the safety profile. RESULTS: All the different PEGylation levels of SN38 prodrug NPs exhibited high drug loading (> 25%) but distinct behaviors depending on the PEGylation level. Low PEGylation (20%) led to poor colloidal stability, reduced cellular uptake, and rapid clearance by the m...