Bola-Amphiphilic Dendrimer Enhances Imatinib to Target Metastatic Ovarian Cancer via β-Catenin-HRP2 Signaling Axis

IF 8.3 2区材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY

ACS Applied Materials & Interfaces Pub Date : 2025-01-03 DOI:10.1021/acsami.4c12857

Zeyu Shi, Margarita Artemenko, Weiyu Yu, Ming Zhang, Canhui Yi, Peng Chen, Shuting Lin, Zhancun Bian, Baoping Lian, Fanzhen Meng, Jiaxuan Chen, Tom Roussel, Ying Li, Karen K. L. Chan, Philip P. C. Ip, Hung-Cheng Lai, Sally K. Y. To, Xiaoxuan Liu, Ling Peng, Alice S. T. Wong

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Abstract

Ovarian cancer is the leading cause of death among all gynecological malignancies, and drug resistance renders the current chemotherapy agents ineffective for patients with advanced metastatic tumors. We report an effective treatment strategy for targeting metastatic ovarian cancer involving a nanoformulation (Bola/IM)─bola-amphiphilic dendrimer (Bola)-encapsulated imatinib (IM)─to target the critical mediator of ovarian cancer stem cells (CSCs) CD117 (c-Kit). Bola/IM offered significantly more effective targeting of CSCs compared to IM alone, through a novel and tumor-specific β-catenin/HRP2 axis, allowing potent inhibition of cancer cell survival, stemness, and metastasis in metastatic and drug-resistant ovarian cancer cells. Promising results were also obtained in clinically relevant patient-derived ascites and organoids alongside high tumor-oriented accumulation and favorable pharmacokinetic properties in mouse models. Furthermore, Bola/IM displayed synergistic anticancer activity when combined with the first-line chemotherapeutic drug cisplatin in patient-derived xenograft mouse models without any adverse effects. Our findings support the use of Bola/IM as a nanoformulation to empower IM, providing targeted and potent treatment of metastatic ovarian cancer. Our study thus represents a significant advancement toward addressing the unmet medical need for improved therapies targeting this challenging disease.

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来源期刊

ACS Applied Materials & Interfaces 工程技术-材料科学：综合

CiteScore

16.00

自引率

6.30%

发文量

4978

审稿时长

1.8 months

期刊介绍： ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.