Development of doxorubicin-loaded chitosan-heparin nanoparticles with selective anticancer efficacy against gastric cancer cells in vitro through regulation of intrinsic apoptosis pathway

Chitosan-heparin nanoparticles (CS-HP NPs) can be used as potential nano-based platforms for development of drug delivery carriers. In this article, doxorubicin (Dox)@CS-HP NPs were synthesized and their physicochemical characteristics were assessed. Afterwards, their anticancer effects against gastric cancer (AGS) cells were assessed by MTT, LDH, ROS, and qPCR assays, whereas peripheral blood mononuclear cells (PBMCs) were used as control normal cells. It was observed that blank CS-HP NPs and Dox@CS-HP NPs showed average hydrodynamic sizes and zeta potential values of 72.95 +/- 9.67 nm (PDI: 0.197), 79.68 +/- 13.11 nm (PDI: 0.227) and 23. 68 +/- 3.69 mV, 19.37 +/- 2.38 mV, respectively and Dox loading capacity (LC) in the CS-HP NPs was 7.3 +/- 1.29% with an entrapment efficacy (EE) of 91.37 +/- 5.27%. It was also seen that lowering the pH to within the range of cancer cells (pH 6.5) and gastric cells (pH 1.5) stimulated substantial release of the drug from Dox@CS-HP NPs relative to physiological pH. The IC50 values of Dox and Dox@CS-HP NPs were observed to be 23.37, 26.14 mu g/ml and 8.57, 4.21 mu g/ml in the case of PBMCs and AGS cells, respectively. It was also showed that Dox@CS-HP NPs increased the LDH release, intracellular reactive oxygen species (ROS), mRNA levels of Bax/Bcl-2, caspase-9, and caspase-3, while did not change the expression of caspase-8 at mRNA level, indicating that Dox@CS-HP NPs activates the intrinsic apoptotic pathway. In general, it can be concluded that Dox@CS-HP NPs can induces selective anticancer effects on AGS cells. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.