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Abstract
Great efforts have been made to develop drug carriers with the aim of providing predictable therapeutic response. Moreover, combination therapies have become promising strategies for clinical cancer treatment with synergistic effects. The present study purposed to develop a new stimuli-responsive paramagnetic nanocarrier for the intracellular co-delivery of doxorubicin (DOX) and methotrexate (MTX) to the MCF7 cell line. A novel thermo/pH-sensitive amphiphilic paramagnetic nanocomposite comprised of hydrophobic and biodegradable PCL segments and a hydrophilic biocompatible P(NIPAAm-co-HEMA-co-MAA-co-TMSPMA) block was designed and synthesized by combining the ring opening and free radical polymerization methods. The structure and physic-chemical characterization of synthesized nanoparticles and intermediates were studied and revealed using FTIR, HNMR, CNMR, SEM, EDX, TGA, and VSM techniques. DOX and MTX on a nanocarrier achieved 95.04 and 97.29% encapsulation efficiency, respectively. The dual drug release profile revealed tumor niche-assisted release behavior (more drug release was observed at a temperature of 41 °C and pH ≤ 5.4). The antitumor ability of the DOX/MTX-loaded nanocomposite was significantly higher than that of free drugs, confirmed by MTT assay, DAPI staining, cell cycle, and real-time PCR analysis on MCF7 cell lines. Furthermore, the cytotoxicity assay of a nanocarrier to the MCF7 cell line revealed its suitability as an anticancer drug nanocarrier. The results indicated that this engineered dual anticancer drug delivery system ensures increased antitumor activity as well as decreased toxicity in comparison with the free drugs.
