Design of Janus-like PMMA-PEG-FA grafted fluorescent carbon dots and their nanoassemblies for leakage-free tumor theranostic application

Theranostic nanomedicines for imaging guided therapy, simultaneously monitoring the real-time response of therapy, have aroused great interest in cancer research. Here, the Janus-like poly(methyl methacrylate)- b -poly(ethylene glycol)-folic acid block -copolymer-grafted fluorescent carbon dots (CDs-PMMA-PEG-FA) were synthesized via surface-initiated atom transfer radical polymerization (SI-ATRP) of methyl methacrylate (MMA) in ethanol with the modified carbon dots (CDs-Br) as initiator, followed by the PEGylation via click chemistry. Interestingly, they could self-assemble into blank nanoassemblies with hydrodynamic diameter of about 150 nm and Doxorubicin (DOX)-loaded nanoassemblies of about 270 nm with high DOX–loading capacity of 67.2%. The DOX-loaded nanoassemblies could release >80% of DOX at pH 5.0 within 36 h, while that at pH 7.4 was only 2%, demonstrating the excellent on-off behavior on pH stimuli. A possible mechanism was proposed to explore the drug release pathway in vitro. Enhanced anti-cancer efficacy of the CDs-PMMA-PEG-FA/DOX nanoassemblies with folate receptor (FR)-mediated targeting function than the free DOX was revealed by the MTT assays, while the bare CDs-PMMA-PEG-FA nanoassemblies possessed good cytocompatibility. The cellular uptake result showed that the proposed fluorescent theranostic nanomedicines could be effectively internalized into HepG2 cells and release DOX into the cell nuclei.