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Engineering anti-c-MET scFv-conjugated PLGA nanoparticles for precision verteporfin delivery in lung cancer cells: a
Alessia Giglio1, Enrica Chiesa1, Luisa Iamele2
1Department of Drug Sciences, University of Pavia, Pavia, Italy.
Abstract:
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.
Insights
Researchers developed a novel nanoparticle platform for lung cancer therapy. This platform selectively targets c-MET overexpressing cancer cells, enabling precise delivery of the antitumor agent verteporfin.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- The tyrosine kinase receptor c-MET is frequently overexpressed in lung cancer, promoting tumor growth and metastasis.
- This overexpression creates a targetable difference between cancer cells and healthy tissue for drug delivery.
Purpose of the Study:
- To design and develop a tunable nanoparticulate platform for selective targeting of c-MET overexpressing lung cancer cells.
- To enable targeted delivery of the antitumor agent verteporfin (VP) using this nanoplatform.
Main Methods:
- Conjugation of a single-chain variable fragment (3H3-HisC scFv) to PLGA-based nanoparticles (NPs).
- Modification of scFv for site-directed conjugation to preserve binding capacity.
- Loading nanoparticles with verteporfin (VP).
Main Results:
- Successful functionalization of NPs with 3H3-HisC scFv and efficient drug loading (3 µg VP/mg NPs).
- Demonstrated enhanced and specific uptake of the nanoplatform into c-MET-overexpressing A549 lung cancer cells in vitro.
- Showcased tunable verteporfin release rates by altering nanoparticle polymer properties.
Conclusions:
- The developed nanoplatform offers a flexible and customizable approach for targeted lung cancer therapy.
- This technology holds promise for selective delivery of cytotoxic agents to c-MET-driven tumors.
- The ability to modulate drug release provides application-specific customization for personalized medicine.
