2. Academic Validation
  3. Bola-Amphiphilic Dendrimer Enhances Imatinib to Target Metastatic Ovarian Cancer via β-Catenin-HRP2 Signaling Axis

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

  • ACS Appl Mater Interfaces. 2025 Jan 15;17(2):2884-2898. doi: 10.1021/acsami.4c12857.
Zeyu Shi 1 2,  Margarita Artemenko 1,  Weiyu Yu 1,  Ming Zhang 1,  Canhui Yi 1,  Peng Chen 3,  Shuting Lin 3,  Zhancun Bian 3 4,  Baoping Lian 3,  Fanzhen Meng 3,  Jiaxuan Chen 3 4,  Tom Roussel 4,  Ying Li 3,  Karen K L Chan 5,  Philip P C Ip 6,  Hung-Cheng Lai 7 8,  Sally K Y To 1 2,  Xiaoxuan Liu 3,  Ling Peng 4,  Alice S T Wong 1
Affiliations

Affiliations

  • 1 School of Biological Sciences, University of Hong Kong, Pokfulam, Hong Kong 999077, China.
  • 2 Laboratory for Synthetic Chemistry and Chemical Biology Limited, Pokfulam, Hong Kong 999077, China.
  • 3 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing 211198, China.
  • 4 Aix-Marseille Université, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, Equipe Labellisée Ligue Contre le Cancer, 13288 Marseille, France.
  • 5 Department of Obstetrics and Gynecology, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong 999077, China.
  • 6 Department of Pathology, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong 999077, China.
  • 7 Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • 8 Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, Taipei 23561, Taiwan.
PMID: 39752231 DOI: 10.1021/acsami.4c12857
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.

Keywords

cancer stem cells; chemoresistance; dendrimer; nanovector; ovarian cancer; targeted therapy.

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