10-Hydroxycamptothecin-Loaded Hollow Mesoporous Polydopamine Modified with ANGPT2-Specific Peptide for Gastric Cancer-Targeted Therapy

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2025-09-15 DOI:10.1021/acs.jmedchem.5c01330

Haidong Tian, , , LanLan Lin, , , Huijun Guo, , , Jiadi Liu, , , Rong Gan, , , Qiyue Zhang, , , Duling Xu, , and , Hongyan Li*,

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引用次数: 0

Abstract

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.

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angpt2特异性肽修饰10-羟基喜树碱中空介孔聚多巴胺用于胃癌靶向治疗

羟基喜树碱（HCPT）的毒副作用限制了其抗肿瘤的临床应用。用angpt2特异性肽GSFIHSVPRH （GSF）修饰中空介孔聚多巴胺（HMPDA）表面，然后装载HCPT和吲哚菁绿（ICG）形成给药系统（ICG-GSF-HMPDA@HCPT）。表征了材料的形貌、粒径、HCPT负载能力和HCPT释放性能。体外和体内实验验证了该递送系统的生物相容性和抗肿瘤功效。微正电子发射断层扫描(PET)/计算机断层扫描（CT）显示，68ga标记的GSF在异种移植物中积累，证实了GSF对胃癌的靶向作用。ICG-GSF-HMPDA@HCPT抑制了HGC-27细胞的活力、集落形成、细胞侵袭和迁移，对异种移植物发育的抑制效果优于HMPDA@HCPT。此外，血液生化分析表明ICG-GSF-HMPDA@HCPT具有良好的生物安全性。因此，用angpt2特异性肽修饰的hcpt负载HMPDA被成功构建，并作为gc靶向治疗的有效递送。

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来源期刊

Journal of Medicinal Chemistry 医学-医药化学

CiteScore

4.00

自引率

11.00%

发文量

804

审稿时长

1.9 months

期刊介绍： The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.