Enhanced cell apoptosis triggered by a multi modal mesoporous amphiphilic drug delivery system

Abstract

Mesoporous magnetic nanoparticles (MMNPs) have been synthesized through a facile soft chemical route and are conjugated with multiple therapeutic agents. These MMNPs have the ability to contain and deliver both hydrophilic and hydrophobic drugs simultaneously with the mediation of an AC magnetic field (ACMF). Furthermore, the synthesis and characterization of doxorubicin hydrochloride:paclitaxel (DOX:TXL) and doxorubicin hydrochloride:cisplatin (DOX:Cis-Pt) conjugates are demonstrated. MMNPs show an excellent loading efficiency of ∼96:83% (DOX:TXL) and ∼93:83% (DOX:Cis-Pt) along with a loading capacity of ∼0.002:0.002 mg mg−1 (DOX:TXL) and ∼0.002:0.002 mg mg−1 (DOX:Cis-Pt), respectively. Over a period of 180 h, a sustained release of drugs is observed and shows a better efficiency at pH 4.3 (∼85:63%-DOX:TXL and ∼86:73%-DOX:Cis-Pt) compared to that under physiological pH conditions (∼28:22%-DOX:TXL and ∼26:22%-DOX:Cis-Pt). The MMNPs can release ∼37:22% (DOX:TXL) and ∼34:25% (DOX:Cis-Pt) within 30 min when triggered by an ACMF (at ∼43 °C). The in vitro cytotoxic effect, the ROS generation level and cell cycle distribution analysis of DOX:TXL-MMNPs and DOX:Cis-Pt-MMNPs treated MDA-MB231, MCF-7 and PC3 cancer cells are demonstrated. Enhanced cell apoptosis is observed by thermo-chemotherapy which includes application of an ACMF for 15 min. Specifically, DOX:TXL-MMNPs are more effective than DOX:Cis-Pt-MMNPs towards the PC3 cell line. The internalization of multiple drug loaded MMNPs by cells and their morphological changes due to thermo-chemotherapy are confirmed through confocal microscopy. From the present results, it is observed that the DOX:TXL and DOX:Cis-Pt conjugated MMNPs, under an ACMF, can readily minimize drug resistance. This has significantly enhanced the cell apoptosis of target cancer cells.