Doxorubicin and siRNA co-delivery System Based on Carbon Dots Inhibits Chemoresistance of Lung Cancer Through MRP1

Abstract

BackgroundAcquired resistance against chemotherapeutic drugs hinders the clinical efficacy of treatments in lung cancer. To circumvent the developed resistance, we aim to target critical signaling molecules related with chemoresistance through co-delivering siRNA and chemotherapeutics. The co-delivery strategy may address the unmet need to efficiently counteracting the multidrug resistance in treating lung cancer. MethodsA co-delivery nanosystem that could carry siRNA and DOX simultaneously has been studied in this work. The co-delivery is based on carbon dots was surface-modified with poly-ethylenimine (PEI), and loaded the siMRP1 and chemotherapeutics 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.ResultsThe CD-PEI was capable of loading and delivering siMRP1 and DOX to tumor and release synchronously in cells by acid-triggered manner.The expression of MRP1 in A549 and A549/ADM cells were successfully knocked down by siRNA. The silencing of MRP1 by co-delivery system could increase DOX accumulation and significantly enhance the inhibitory effect of cell viability. Moreover, the co-delivery system enhances the inhibitory effect of metastatic potential elicited by doxorubicin in A549 and A549/ADM cells.ConclusionBy suppressing MRP1, the co-delivery system can obviously increase the drug cellular accumulation and inhibit the cell proliferation, migration and invasion of lung cancer, implying its potential application to overcome chemoresistance and enhance therapeutic efficiency in clinical practices.