Journal of medicinal chemistry · 2025
10-Hydroxycamptothecin-Loaded Hollow Mesoporous Polydopamine Modified with ANGPT2-Specific Peptide for Gastric Cancer-Targeted Therapy.
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Tian Haidong, Lin LanLan, Guo Huijun, Liu Jiadi, Gan Rong, Zhang Qiyue, Xu Duling, Li Hongyan
Аннотация
The side effects of hydroxycamptothecin (HCPT) limit its clinical application in antitumor. The surface of hollow mesoporous polydopamine (HMPDA) was modified with the ANGPT2-specific peptide GSFIHSVPRH (GSF), followed by loading HCPT and indocyanine green (ICG) to form a drug-delivery system (ICG-GSF-HMPDA@HCPT). The morphology, particle size, HCPT loading capacity, and HCPT-release properties were characterized. The biocompatibility and antitumor efficacy of the delivery system were validated through in vitro and in vivo experiments. Micropositron emission tomography (PET)/computed tomography (CT) imaging showed that 68Ga-labeled GSF accumulated in the xenograft, and the targeting of GSF toward gastric cancer was confirmed. ICG-GSF-HMPDA@HCPT inhibited cell viability, colony formation, cell invasion, and migration of HGC-27 cells and showed a better suppression of xenograft development than HMPDA@HCPT. Furthermore, blood biochemical assays showed that ICG-GSF-HMPDA@HCPT exhibited favorable biosafety. Thus, the HCPT-loaded HMPDA modified with the ANGPT2-specific peptide was successfully constructed and served as a potent delivery for GC-targeted therapy.