Investigation on a smart nanocarrier with a mesoporous magnetic core and thermo-responsive shell for co-delivery of doxorubicin and curcumin: A new approach towards combination therapy of cancer

Abstract

In this work, we report on the synthesis and characterization of a novel and smart nanocarrier with a mesoporous magnetic core and thermo-responsive shell for co-delivery of hydrophilic doxorubicin (Dox) and hydrophobic curcumin (Cur) as a combinational therapy for cancer treatment. The P(NIPAM-MAm) coated mesoporous Fe3O4 (MIO-P(NIPAM-MAm)) nanocomposite was prepared by in situ cross linked polymerization of NIPAM and MAm on the surface of pre-synthesized mesoporous Fe3O4 nanoparticles (MIO NPs) in the presence of an oxidizer and cross linker. MIO NPs were synthesised by co-precipitation method using CTAB as the sacrificial soft template. Different characterization techniques have been used to study the physicochemical properties of MIO NPs and the MIO-P(NIPAM-MAm) nanocomposite. Particle sizes of the MIO-P(NIPAM-MAm) nanocomposite estimated by TEM were found to be in between 200-500 nm. VSM results show MIO and MIO-P(NIPAM-MAm) nanocomposites to be superparamagnetic in nature. MIO-P(NIPAM-MAm) nanocomposites exhibited a lower critical solution temperature (LCST) of 41 °C, which is suitable for controlled drug delivery applications unlike pure PNIPAM based nanocarriers. The encapsulation efficiency of Dox and Cur were found to be 96% and 90% respectively. Temperature dependent release studies from MIO-P(NIPAM-MAm)-Cur-Dox indicated a slower release of drugs (both Dox and Cur) below LCST and a sustained release above LCST. Different mathematical models (such as zero order, first order, Higuchi and Korsmeyer-Peppas) were used to fit the experimental release profiles of both drugs. MTT assays on normal and HeLa cells demonstrated the non-toxic nature of the MIO-P(NIPAM-MAm) nanocomposite. The co-loaded MIO-P(NIPAM-MAm)-Cur-Dox nanocomposite exhibited higher in vitro anti-cancer activity compared to free Dox, free Cur, and a free Dox + free Cur mixture. Such a co-loaded smart delivery system could have potential for controlled and targeted drug delivery in cancer diagnosis.