Chrysin-Loaded Micelles Regulate Cell Cycle and Induce Intrinsic and Extrinsic Apoptosis in Ovarian Cancer Cells

Cakir S., Yildiz U., Yildirim T., AYDIN Ö.

Nanomaterials, cilt.15, sa.17, 2025 (SCI-Expanded, Scopus) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 15 Sayı: 17
  • Basım Tarihi: 2025
  • Doi Numarası: 10.3390/nano15171362
  • Dergi Adı: Nanomaterials
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Chemical Abstracts Core, Communication Abstracts, Food Science & Technology Abstracts, INSPEC, Metadex, Directory of Open Access Journals, Civil Engineering Abstracts
  • Anahtar Kelimeler: raft polymerization, nanoprecipitation, chrysin, cell cycle, apoptosis, ovarian cancer
  • Erciyes Üniversitesi Adresli: Evet

Özet

Effective intracellular delivery for ovarian cancer therapy remains a significant challenge. We present chrysin-loaded p(MMA-co-DMAEMA)-b-(OEGMA-co-DMA), PMOD-Chr, a nanoparticle platform precisely engineered via RAFT polymerization for advanced therapeutic delivery. This multi-functional platform features a hydrophobic p(MMA) core encapsulating chrysin (Chr), a pH-responsive p(DMAEMA) segment for endosomal escape, and a hydrophilic OEGMA (Oligo(ethylene glycol) methyl ether methacrylate) shell functionalized for enhanced cellular affinity and systemic stability. The combination of OEGMA and DMA (Dopamine methacrylamide) block facilitates passive targeting of ovarian cancer cells, enhancing internalization. Nanoparticles prepared via the nanoprecipitation method exhibited ~220 nm, demonstrating effective size modulation along with high homogeneity and spherical morphology. In A2780 and OVCAR3 ovarian cancer cells, PMOD-Chr demonstrated significantly enhanced cytotoxicity, substantially lowering the effective IC50 dose of Chr. Mechanistically, PMOD-Chr induced a potent G2/M cell cycle arrest, driven by the upregulation of the CDK1/Cyclin B1 complex. Furthermore, the formulation potently triggered programmed cell death by concurrently activating both the intrinsic apoptotic pathway, evidenced by the modulation of Bax, Bcl2, and caspase 9, and the extrinsic pathway involving caspase 8. These findings emphasize that precision engineering via RAFT polymerization enables the creation of sophisticated, multi-stage nanomedicines that effectively overcome key delivery barriers, offering a highly promising targeted strategy for ovarian cancer.