Supramolecular Nanomedicine Constructed from Cucurbit[8]uril-Based Amphiphilic Brush Copolymer for Cancer Therapy

An amphiphilic supramolecular brush copolymer CB[8]D(PEG-Np center dot PTPE) was constructed on the basis of a novel host guest molecular recognition model formed by cucurbit[8]uril (CB[8]), 4,4'-bipyridinium derivative, and PEGylated naphthol (PEG-Np). In aqueous solution, the resultant supramolecular brush copolymer self-assembled into supramolecular nanoparticles (SNPs), by which the anticancer drug doxorubicin (DOX) was encapsulated in the hydrophobic core, establishing an artful Forster resonance energy transfer system with dual fluorescence quenched. With the help of intracellular reducing agents and low pH environment, the SNPs disassembled and the loaded drug molecules were released, realizing in situ visualization of the drug release via the location and magnitude of the energy transfer-dependent fluorescence variation. The cytotoxicity evaluation indicated DOX-loaded SNPs effectively inhibited cell proliferation against HeLa cells. Animal experiments demonstrated that these DOX-loaded SNPs highly accumulated in tumor tissues through the enhanced permeability and retention effect and also had a long blood circulation time. These multifunctional supramolecular nanoparticles possessing self-imaging and controllable drug release ability exhibited great potential in cancer therapy.