Unraveling Cell-Type-Specific Targeted Delivery of Membrane-Camouflaged Nanoparticles with Plasmonic Imaging

Cell-membrane-camouflaged nanoparticles (CMC-NPs) have been increasingly exploited to develop various therapeutic tools due to their high biocompatibility and cell-type-specific tumor-targeting properties. However, the molecular mechanism of CMC-NPs for homotypic targeting remains elusive. Here, we develop a plasmonic imaging method by coating gold nanoparticles (AuNPs) with cancer cell membranes and perform plasmonic imaging of the interactions between CMC-NPs and living cells at the single-cell level. Quantitative analysis of CMC-NPs in a different clustering status reveals that the presence of cell membranes on CMC-NPs results in a 7-fold increase in homotypic cell delivery and nearly 2 orders of magnitude acceleration of the intracellular agglomeration process. Significantly, we identify that integrin α_vβ₃, a cell surface receptor abundantly expressed in tumor cells, is critical for the selective cell recognition of CMC-NPs. We thus establish a single-cell plasmonic imaging platform for probing NP–cell interactions, which sheds new light on the therapeutic applications of CMC-NPs.