Doxorubicin and siRNA Co-Delivery System Based on Carbon Dots Inhibits Chemoresistance of Lung Cancer

Abstract BackgroundThe resistance to the anti-cancer agent limits the chemotherapy effect in the cancer therapy. Tumor easily develops resistance to anti-cancer drugs leading to decreased therapy efficiency of chemotherapies. Targeting signaling molecules related with chemoresistance through strategy of co-delivery siRNA and chemotherapeutics may overcome the multidrug resistance to chemotherapy. A co-delivery nanosystem that could carry siRNA and DOX simultaneously has been studied in this work. ResultsThe co-delivery is based on carbon dots was surface-modified with poly-ethylenimine (PEI), and loaded the siMRP1 and chemotherapeutics by electronstatic interactions on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI were raw materials and passivator during the reaction process that makes CD exhibit excellent optical property and the capability of loading siRNA. The CD-PEI was capable of loading and delivering siMRP1 and DOX to tumor and release synchronously in cell by pH-triggered manner using flow cytometry and confocal laser scanning microscopy analysis. MRP1 was successfully knocked down by siRNA. The silencing of MRP1 by co-delivery system could increase DOX accumulation and significantly enhance the inhibitory effect of metastatic potential elicited by doxorubicin in A549 and A549/ADM cells.ConclusionThe co-delivery systems effectively loaded and released siRNA and DOX agents to the targeted tumor, overcoming the resistant to chemotherapy. By suppressing MRP1, CD-PEI-DOX-siMRP1 can obviously increase the drug intercellular accumulation and inhibit the cell proliferation, migration and invasion, implying its potential application in enhancing therapeutic efficiency in clinical practices.