Combination Chemotherapy of Lung Cancer – Co-Delivery of Docetaxel Prodrug and Cisplatin Using Aptamer-Decorated Lipid–Polymer Hybrid Nanoparticles

Abstract

Purpose

Lung cancer is the leading cause of cancer mortality worldwide. Drug resistance is the major barrier for the treatment of non-small cell lung cancer (NSCLC). The aim of this research is to develop an aptamer-decorated hybrid nanoparticle for the co-delivery of docetaxel prodrug (DTXp) and cisplatin (DDP) and to treat lung cancer.

Materials and Methods

Aptamer-conjugated lipid–polymer ligands and redox-sensitive docetaxel prodrug were synthesized. DTXp and DDP were loaded into the lipid–polymer hybrid nanoparticles (LPHNs). The targeted efficiency of aptamer-decorated, DTXp and DDP co-encapsulated LPHNs (APT-DTXp/DDP-LPHNs) was determined by performing a cell uptake assay by flow cytometry-based analysis. In vivo biodistribution and anticancer efficiency of APT-DTXp/DDP-LPHNs were evaluated on NSCLC-bearing mice xenograft.

Results

APT-DTXp/DDP-LPHNs had a particle size of 213.5 ± 5.3 nm, with a zeta potential of 15.9 ± 1.9 mV. APT-DTXp/DDP-LPHNs exhibited a significantly enhanced cytotoxicity (drug concentration causing 50% inhibition was 0.71 ± 0.09 μg/mL), synergy antitumor effect (combination index was 0.62), and profound tumor inhibition ability (tumor inhibition ratio of 81.4%) compared with the non-aptamer-decorated LPHNs and single drug-loaded LPHNs.

Conclusion

Since the synergistic effect of the drugs was found in this system, it would have great potential to inhibit lung tumor cells and in vivo tumor growth.

Keywords:

• lung cancer
• combination therapy
• docetaxel prodrug
• cisplatin
• aptamer-decorated
• lipid–polymer hybrid nanoparticles

Disclosure

Ruifeng Wu and Zhiqiang Zhang are co-first authors. The authors report no conflicts of interest in this work.