Bone-targeted stimuli-responsive polymeric nanocarriers for osteosarcoma treatment


Mutlu I., Gencoglu-Katmerlikaya T., ATASOY S., DAĞ A.

JOURNAL OF MACROMOLECULAR SCIENCE PART A-PURE AND APPLIED CHEMISTRY, cilt.62, sa.12, ss.1238-1250, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 62 Sayı: 12
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1080/10601325.2025.2571964
  • Dergi Adı: JOURNAL OF MACROMOLECULAR SCIENCE PART A-PURE AND APPLIED CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, Aerospace Database, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, Communication Abstracts, Compendex, Metadex, Civil Engineering Abstracts
  • Sayfa Sayıları: ss.1238-1250
  • Anahtar Kelimeler: Alendronate, bone-targeted, doxorubicin, dual drug delivery, osteosarcoma, pH sensitive
  • Bezmiâlem Vakıf Üniversitesi Adresli: Evet

Özet

Osteosarcoma, a highly aggressive bone tumor commonly diagnosed in adolescence, has major treatment challenges due to metastasis and chemoresistance. This study presents the development of bone-targeted, pH-sensitive polymeric dual drug delivery systems based on a triblock copolymer, P(BPMA-b-OEGMEMA-b-FPMA), synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. After deprotection of the BPMA segments, the chemotherapeutic agent doxorubicin (Dox) and/or the bone-targeting drug alendronate (Aln) were loaded onto the polymer, resulting in self-assembled nanomicelles. Dynamic light scattering (DLS) analysis showed that the hydrodynamic diameters of the Dox-loaded (M1), Aln-loaded (M2), and dual drug-loaded (M3) micelles were approximately 100.00 +/- 6.34 nm, 97.70 +/- 4.39 nm, and 89.86 +/- 4.77 nm, respectively, with narrow size distributions. In vitro cytotoxicity assays demonstrated that the dual-loaded micelles (M3) exhibited significantly higher selective toxicity against SAOS-2 osteosarcoma cells compared to free drugs, while maintaining low toxicity toward healthy HUVEC endothelial cells. Cellular uptake studies confirmed enhanced internalization of the bone-targeted nanocarriers by SAOS-2 cells. These findings highlight the potential of this novel polymeric system to improve therapeutic outcomes by effectively targeting bone tumor cells and minimizing side effects through controlled and selective drug delivery.