Dendritic Platinum Nanoparticles Shielded by Pt‐S PEGylation as Intracellular Reactors for Bioorthogonal Uncaging Chemistry

Beyond their classical role as cytotoxics, Platinum (Pt) coordination complexes recently joined the selected group of transition metals capable of performing bioorthogonal reactions in living environments. To minimize their reactivity towards nucleophiles, which limit their catalytic performance, we investigated the use of Pt(0) with different forms, sizes and surface functionalization. We report herein the development of PEGylated Pt nanodendrites with the capacity to activate prodyes and prodrugs in cell culture and in vivo. Their dendritic morphology together with their surface shielding through Pt-S-bonded PEGylation synergistically contributed to create catalytic nanoreactors compatible with the highly-crowded and reductive environment of the cell cytoplasm, thereby facilitating in situ bioorthogonal drug uncaging in cancer cells in 2D and 3D culture, including in microfluidic systems, and xenografted in zebrafish.