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Multi-drug resistance (MDR) is the major hindrance towards the successful treatment of malignant lung cancer. The aim of this study was to develop a novel nanoparticle co-loaded with docetaxel (DTX) and si-colon cancer-associated transcript-2 (siCCAT2) (NP-DTX/siCCAT2) for overcoming the DTX-resistant non-small cell lung cancer (NSCLC). The NP-DTX/siCCAT2, developed by DTX-conjugated poly (D,L-lactic-co-glycolic acid) (PLGA) copolymers, has an average size of  t  87.26 nm. Further modification of Transferrin (Tf) peptides on the surface of NP-DTX/siCCAT2 did not significantly change the particle size with an average diameter of 96.81 nm. The present study demonstrated that TfNP-DTX/siCCAT2 has excellent tumour targeting ability and resulted in an enhanced anti-tumour effect both  in vitro  and  in vivo  experiments. Not unexpectedly, a more excellent anti-tumour effect of NP-DTX/siCCAT2 was obtained than the NP-DTX because the silencing of CCAT2 levels in lung cancer cells resulted in down-regulated expressions of P-glycoprotein (P-gp) and multidrug-resistance-associated proteins 1 (MRP1). Further investigation revealed that inhibition of CCAT2 expression dramatically increased the activity of miR-204-3p and thereby signally suppressed the IGFBP2/AKT/Bcl2 pathway.

Tumour targeted polymer nanoparticles co-loaded with docetaxel and siCCAT2 for combination therapy of lung cancer