Ligand-conjugated pH-sensitive polymeric micelles for the targeted delivery of gefitinib in lung cancers

Abstract

The aim of the present study was to investigate the tumor targeting potential of a mannose-conjugated pH-sensitive nanosystem for the effective delivery of gefitinib (Gnb) to lung cancers. We have successfully demonstrated the potential of mannose-tagged nanomicelles as an efficient vector to transport the anticancer drug. The micelles had nanosized particles with excellent dispersity index. The nanomicelles exhibited a pH-responsive nature with enhanced drug release in acidic pH conditions. Fluorescence and flow cytometer analysis showed a superior cellular uptake for the mannose-tagged nanomicelles. Confocal laser scanning microscopy study revealed a receptor-mediated cellular internalization process. The M-NP-Gnb showed a superior anticancer effect in A549 cancer cells and remarkably inhibited cancer cell proliferation. Furthermore, M-NP-Gnb significantly increased the proportion of cells in the apoptosis and necrosis region. Importantly, the half-life of Gnb encapsulated in nanomicelles increased by about 5-fold compared to that of free Gnb. The augmented half-life clearly indicates the maximum residence time of the drug in the systemic circulation. Consistently, M-NP-Gnb showed a 7-fold higher accumulation of drug in tumor tissues compared to that of free Gnb. Overall, PLGA/His-based nanomicelles could be a promising delivery system to increase the therapeutic efficiency of Gnb in lung cancers.