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Context: Paclitaxel (PTX) and carboplatin (CBP) are widely used for the combined chemotherapy of non-small cell lung cancer (NSCLC). However, the development of multidrug resistance of cancer cells, as well as systemic toxic side effects resulting from nonspecific localization of anticancer drugs to non-tumor areas are major obstacles to the success of chemotherapy in treating cancers. Objective: This study aimed to engineer a prodrug-based nano-drug delivery system for co-encapsulate hydrophilic (CBP) and hydrophobic anti-tumor drugs (PTX). This system was expected to resolve the multidrug resistance cause by single drug, and the dual-drug-loaded liposome was also planned to specifically target the cancer cells without obvious influence on normal cells and tissues. Methods: In this paper, PLGA-PEG-CBP was synthesized by the conjugation between the carboxylic group of PLGA-PEG-COOH and the amino group of CBP. Then, self-assembled nanoparticles for combination delivery of PTX and PLGA-PEG-CBP (PTX/CBP NPs) were prepared by solvent displacement technique. Thein vitroandin vivoanti-tumor efficacy was assessed in NCL-H460 human non-small cell lung carcinoma cell line. Results: PTX/CBP NPs achieved the highest cytotoxic effect among all formulationsin vitro, as compared with single drug delivery NPs.In vivoinvestigation on NSCLC animal models showed that co-delivery of PTX and CBP possessed high tumor-targeting capacity and strong anti-tumor activity. Conclusions: The PTX/CBP NPs constructed in this research offers an effective strategy for targeted combinational lung cancer therapy. [ABSTRACT FROM AUTHOR]