Abstract
Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers diagnosed worldwide, yet managing it is still challenging. The epidermal growth factor receptor (EGFR) exhibits aberrant signalling in a wide range of human cancers, and it is reported to overexpress in most NSCLC cases. The monoclonal antibody [Cetuximab (Cet)] was conjugated onto the surface of the poly (lactide-co-glycolide) (PLGA) nanoparticles which were loaded with docetaxel (DTX) for the development of targeted therapy against lung cancer. This site-specific delivery system exhibited an enhanced cellular uptake in lung cancer cells which overexpress EGFR (A549 and NCI-H23). The nanoparticles also showed better therapeutic effectiveness against NSCLC cells, as evidenced by reduced IC50 values, cell cycle arrest at the G2/M phase, and increased apoptosis. The improved efficacy and in vivo tolerance of Cet-DTX NPs were demonstrated in benzo(a)pyrene (BaP)-induced lung cancer mice model. Histopathological analysis showed that intravenous injection of Cet-DTX NP to mice carrying lung cancer greatly reduced tumour development and proliferation. Comparing Cet-DTX NP to free drug and unconjugated nanoparticles, it also had negligible side effects and improved survival rates. Therefore, Cet-DTX NPs present a promising active targeting carrier for lung tumour-NSCLC-selective treatment.
Graphical Abstract
Acknowledgements
The authors thank Dr. Hemant R. Badwaik and Barnali M. Sinha for their technical assistance.
Disclosure statement
No potential conflict of interest was reported by the authors.
Authors’ contributions
Leena Kumari and Biswajit Mukherjee contributed to funding acquisition, study conception and design, manuscript drafting, and critical revision; Leena Kumari, Iman Ehsan, Arunima Mondal, and Ashique Al Hoque contributed to the analysis and interpretation of data; Pritha Choudhury, Arunima Sengupta, Ramkrishna Sen, and Prasanta Ghosh contributed in experiments, drafting and revising the work; Leena Kumari contributed in agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.