Programmable nanoparticle functionalization for in vivo targeting

The emerging demand for programmable functionalization of existing base nanocarriers necessitates development of an efficient approach for cargo loading that avoids nanoparticle redesign for each individual application. Herein, we demonstrate in vivo a postformulation strategy for lipidic nanocarrier functionalization with the use of a linker peptide, which rapidly and stably integrates cargos into lipidic membranes of nanocarriers after simple mixing through a self‐assembling process. We exemplified this strategy by generating a VCAM‐1‐targeted perfluorocarbon nanoparticle for in vivo targeting in atherosclerosis (ApoE‐deficient) and breast cancer (STAT‐1‐deficient) models. In the atherosclerotic model, a 4.1‐fold augmentation in binding to affected aortas was observed for targeted vs. nontargeted nanoparticles (P