Co-delivery of Gefitinib and chloroquine by chitosan nanoparticles for overcoming the drug acquired resistance

BACKGROUND Acquired drug resistance is becoming common during cancer chemotherapy and leads to treatment failure in clinic. To conquer acquired drug resistance, nanotechnology has been employed to deliver drug. In this paper, we prepared chitosan nanoparticles (CS NPs) capable of entrapping Gefitinib and chloroquine (CQ) for multiple drugs combinational therapy. RESULTS The results showed that Gefitinib/CQ-NPs were characterized of small particle size about 80.8 ± 9.7 nm and positive zeta potential about 21.3 ± 1.56 mV, and drug controlled to release slowly on a biphasic pattern. Compared with free Gefitinib and Gefitinib loaded NPs, Gefitinib and CQ co-delivery by CS nanoparticles showed the higher inhibition rates and enhanced cell apoptosis. Through western blot analysis, we found that Gefitinib could promote LC3 expression, which is the marker of autophagosomes. So, the acquired drug resistance may be associated with autophagy. CQ as an inhibitor of autophagolysosomes formation could overcome autophagy in the resistant cells. CONCLUSIONS These findings demonstrated that chitosan nanoparticles entrapping Gefitinib and chloroquine have the potential to overcome acquired resistance and improve cancer treatment efficacy, especially towards resistant strains. Graphical abstract: Cellular distribution of NPs after incubating QGY (a) and QGY/Gefitinib cells (b) with rhodamine B-labeled NPs.