Smart thermo/pH responsive magnetic nanogels for the simultaneous delivery of doxorubicin and methotrexate.

Two novel dual temperature/pH-sensitive superparamagnetic nanogels were developed with the aim of simultaneously delivering two different anticancer drugs, doxorubicin (DOX) and methotrexate (MTX). The studied copolymers were characterized by (1)H NMR, SEM, and FTIR spectroscopy. Morphological investigations showed that both blank and drug-loaded nanogels had uniform shapes with a mean diameter of less than 30 nm. The drug storage/release behaviors were investigated. The nanogels showed an encapsulation efficiency of about 95% for both drugs. The cumulative in vitro release of the DOX/MTX-loaded nanogels exhibited an apparent thermo/pH-triggered controlled drug release in a sustained manner that was able to distinguish between tumor tissues. The cytotoxicity assay of a blank carrier to MCF7 and MDA-MB-231 cell lines indicated that the nanogels were suitable as drug carriers. Cell viability experiments further confirmed that the co-administration of DOX with MTX had a superior cytotoxicity to the mentioned cells compared with free dual drug- or single drug-loaded forms. Therefore, dual anticancer drug-loaded thermo/pH-sensitive nanogels have the potential to be used for cancer therapy, because they maintain a low premature drug release during blood circulation while having a rapid release upon reaching tumorous tissue.