Super homotypic targeting by exosome surface engineering

Homotypic targeting is the inherent ability of cells for preferential interaction with cells of similar or identical types, a phenomenon commonly seen in cell adhesion, tissue formation, and immune responses. Unfortunately, its full potential remains largely untapped. Here we introduce an approach to drastically boost the homotypic targeting capabilities of cells via exosomes (nanoscale extracellular vesicles secreted by cells). By engineering exosome surfaces with lanthanides, we amplify specific cell-exosome interactions by more than 25-fold, significantly accelerating the selective capture of exosomes by cells of the same lineage. This substantial enhancement in cellular homophilicity opens up an entirely new class of applications, two of which we showcase here with unprecedented performance: using cells to detect specific exosomes and using exosomes to detect specific cells. The concept of “super homotypic targeting” offers enormous potential to transform cancer diagnostics, immunotherapy, targeted drug delivery, tissue engineering, and vaccine development. ### Competing Interest Statement H.-S.W., Y.L., T.D., S.S., and K.G. are inventors on a patent covering the exosome detection method. K.G. is an inventor on a patent covering the VIFFI imaging flow cytometer. N.N. and K.G. are shareholders of CYBO. M.S. and K.G. are shareholders of FlyWorks, Inc.