| 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/pHsensitive 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 efciency, respectively. The dual drug
release profle 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
signifcantly higher than that of free drugs, confrmed 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. |