Molecularly targeted gemcitabine-loaded nanoparticulate system towards the treatment of EGFR overexpressing lung cancer

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Xian-Bao Wang, Hai-Yan Zhou

Abstract

Molecularly targeted therapy emerged as a novel therapeutic strategy in the treatment of multiple cancers. In the present study, we have developed gemcitabine (GEM)-loaded cetuximab (CET) surface modified poly(lactic) acid (PLA) nanoparticles (NP) (CET-GEM/PLA NP) to target to epidermal growth factor receptor (EGFR) overexpressing non-small cell lung cancer (A549) cells. The resultant CET-GEM/PLA NP showed a very uniform particle size of∼120 nm and spherical morphology. It exhibited a pH-dependent controlled release pattern. A sustained release of drug in the physiological conditions and faster release in tumor pH will greatly improve the chemotherapeutic efficiency of therapeutic system. Higher or enhanced cellular uptake of CET-GEM/PLA NP in A549 cancer cells clearly indicates the EGFR-mediated receptor based active targeting. Nearly, a two-fold increase in fluorescent intensity was observed for CET-GEM/PLA NP comparing to that of non-targeted NP in the cancer cells. EGFR-mediated internalization of the targeted NP was further confirmed by the confocal microscopy. MTT assay clearly showed the enhanced cell killing effect of CET-conjugated NP due to the selective delivery of GEM to the EGFR over expressing cancer cells. Finall...Continue Reading

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Citations

May 27, 2016·Analytical and Bioanalytical Chemistry·Gabriele Dadalt SoutoHugh James Byrne
Oct 25, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zheng TaoHaitao Ma
Feb 6, 2017·Journal of Drug Targeting·Asadullah MadniAhmad Raza
Nov 14, 2018·Expert Opinion on Drug Delivery·Nasser AlhajjPaolo Colombo
Oct 26, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Özge ErSanti Nonell
Sep 28, 2021·International Journal of Pharmaceutics·Phuoc Vinh NguyenEmilie Allard-Vannier

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