PLA-based magnetic nanoparticles armed with thermo/pH responsive polymers for combination cancer chemotherapy

Abstract

A novel thermo/pH sensitive amphiphilic copolymer of Fe3O4@PLA-g-P(NIPAAm-co-HEMA-co-MAA-co-TMSPMA) magnetic nanoparticles comprised of hydrophobic and biodegradable PLA block and hydrophilic P (NIPAAm-co-HEMA-co-MAA-co-TMSPMA) segment was designed and synthesized by combination of ring opening and free radical polymerization methods. The structure and physic-chemical characterization of synthesized nanoparticles were studied and revealed by FTIR, 1HNMR, 13CNMR, SEM, EDX, TEM, DLS-Zeta, XRD, TGA and VSM techniques. Two cationic and anionic anti-cancer drugs of doxorubicin (DOX) and methotrexate (MTX) were loaded simultaneously to nanocomposite for combination cancer chemotherapy proposes. Nanoparticles showed spherical core-shell structure with particle size below 100 nm confirmed with SEM, TEM, DLS and XRD techniques. Encapsulation efficiency of DOX and MTX on nanocarrier was 95.04% and 97.29%, respectively. Dual drug release profile revealed tumor niche assisted release behaviour. Cytotoxicity studies revealed the non-toxicity of novel developed nanocomposite here to MCF-7 cell lines. Antitumor property of DOX/MTX-loaded nanocomposite was significantly higher than free drugs confirmed by MTT assay, DAPI staining, cell cycle, and real-time PCR analysis on MCF7 cell lines. The results of this study showed that this engineered nanocomposite could be effectively used in the targeted delivery of DOX and MTX to the cancerous tissues and for further in vivo uses.