Nanomedicine emerged 20 years ago promising selective drug delivery, but few nanomedicines have reached patients. Their screening is usually done in 2D cell cultures, which are far from 3D reality. Organ-on-a-chip (OOAC) technology offers models closer to the disease, but it is complex and hard to parallelize, so it is not high-throughput. DNA-PAINT microscopy, thanks to its programmability and high multiplexing capacity, could solve this problem: short oligonucleotide sequences make it possible to barcode hundreds or thousands of nanoparticles (NPs) and analyze them simultaneously in a one-pot assay that reports which NP it is and where it is located. This project combines super-resolution microscopy and OOAC to screen anti-cancer nanomedicines in a single step. NP libraries will be prepared by varying size, geometry, and ligands, and evaluated in a breast-cancer-on-a-chip model including a tumor spheroid, stromal cells, and tumor ECM. This will provide multiparametric information on distribution, extravasation, selectivity, and efficacy, supporting a more rational design of nanomedicines.

Ayuda MCIN/AEI/10.13039/501100011033 Unión Europea «Next Generation EU»/PRTR financiada por: