Peptidic Monodisperse PEG “Comb” as Multifunctional “Add‐On” Module for Imaging‐Traceable and Thermo‐Responsive Theranostics

Monodisperse polyethylene glycols–modified (M‐PEGylated) biomaterials exhibit high structural accuracy, biocompatibility, and fine‐tunable physicochemical properties. To develop “smart” drug delivery systems in a controllable and convenient manner, a peptidic M‐PEG “comb” with fluorinated L ‐lysine side chains and a fluorescent N ‐terminal is conveniently prepared as a 19 F magnetic resonance imaging ( 19 F MRI) and fluorescence dual‐imaging traceable and thermo‐responsive “add‐on” module for liposomal theranostics in cancer therapy. The peptidic M‐PEG “comb” has high biocompatibility, thermo‐responsivity with a sharp lower critical solution temperature, an aggregation‐induced emission fluorescence, and high 19 F MRI sensitivity. As a highly branched amphiphile, it self‐assembles and firmly anchors on the doxorubicin‐loaded liposomal nanoparticles, which M‐PEGylates the liposomes and facilitates the thermo‐responsive drug release and drug tracking with dual‐imaging technologies. In a rodent xenograft model of human liver cancer HepG2 cells, the M‐PEGylated liposomes exhibit long in vivo half time, low toxicity, high tumor accumulation, “hot spot” 19 F MRI, and therapeutic efficacy. With accurately programmable chemical structure, fine‐tunable physicochemical and biological properties to meet the demands of diagnosis, drug delivery, and therapy, the M‐PEG “comb” is promising as a versatile “add‐on” module for rapid and convenient formulation of various “smart” theranostics.