Engineering anti-c-MET scFv-conjugated PLGA nanoparticles for precision verteporfin delivery in lung cancer cells: a formulation study

In lung cancer, the tyrosine kinase receptor c-MET is often overexpressed, driving tumour progression and metastasis. This aberrant surface expression distinguishes the tumour cells from surrounding healthy tissue, providing an opportunity for targeted delivery of cytotoxic agents. This study aimed at designing and developing a tailor-made engineered nanoparticulate platform tuneable for the selective targeting of c-MET overexpressing cells. For this purpose, an effective conjugation method of a potent in-house developed single-chain variable fragment (3H3-HisC scFv) with PLGA-based nanoparticles (NPs) was set up for targeted delivery of the antitumor agent verteporfin (VP) to lung cancer cells (A549). The 3H3-HisC scFv was modified to allow site-directed sulfhydryl-reactive conjugation at the C-terminus, preserving its integrity and binding capacity. Comprehensive characterization confirmed the NP functionalization and drug-loading efficiency (3 µg VP/mg NPs). When tested in vitro, the nanoplatform demonstrated specific enhanced uptake into c-MET-overexpressing A549 cells after 1 h of incubation. A key advantage of this nanoplatform is its flexibility in modulating the VP release rate by adjusting the structural polymer's Mw or L:G ratio, without altering the functionalization, allowing for application-specific customization.