Targeted glutathione-responsive diblock copolymer micelles for efficient zinc phthalocyanine delivery in glioblastoma photodynamic therapy
European Polymer Journal, cilt.256, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 256
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.eurpolymj.2026.115009
- Dergi Adı: European Polymer Journal
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO)
- Anahtar Kelimeler: Glioblastoma, Glutathione-responsive, Photodynamic therapy, Polymeric micelle, Poly[N-(2-hydroxypropyl)methacrylamide], Poly[oligo(ethylene glycol) methyl ether methacrylate], Zinc phthalocyanine
- Yıldız Teknik Üniversitesi Adresli: Evet
Özet
The incorporation of photodynamic therapy (PDT) into polymer-based drug delivery platforms represents a sophisticated therapeutic approach for glioblastoma, facilitating enhanced photosensitizer solubility, improved biocompatibility, and efficient tumor-specific delivery via active and passive targeting pathways. Herein, we report for the first time a glutathione-responsive and actively targeted micellar platform for PDT, in which zinc phthalocyanine (ZnPc) was covalently linked to pOEGMA-b-pHPMA diblock copolymers through redox-cleavable disulfide bonds and subsequently functionalized with Angiopep-2 for enhanced glioblastoma targeting. The pOEGMA-b-pHPMA copolymer was synthesized by RAFT polymerization employing pOEGMA as a macroRAFT agent, whereas cystamine-functionalized ZnPc was synthesized from ZnPc derivatives before micellization. Upon conjugation of ZnPc to the diblock copolymer, Angiopep-2 functionalization was performed to facilitate blood–brain barrier penetration and improve active tumor targeting efficiency in glioblastoma. Angiopep-2-functionalized and non-functionalized micelles were successfully fabricated using the nanoprecipitation technique, and their critical micelle concentrations (cmc) were determined by dynamic light scattering (DLS) spectroscopy as 0.025 and 0.012 mg/mL, respectively.According to the in vitro studies performed on U87-MG glioblastoma cells and HUVEC healthy cells, the developed micellar systems exhibited favorable biocompatibility toward healthy cells while generating significantly higher intracellular reactive oxygen species (ROS) levels in cancer cells under photodynamic irradiation compared with free ZnPc. Furthermore, the targeted micellar formulation induced enhanced photoinduced cytotoxicity against U87-MG cells, which was attributed to its improved cellular internalization efficiency.