Supramolecular assemblies with aggregation-induced emission for in situ active imaging-guided photodynamic therapy of cancer cells.

Photodynamic therapy (PDT) has attracted widespread attention as a novel non-invasive anticancer approach. However, the diminished photosensitivity and limited oxygen exposure caused by the aggregation of traditional photosensitizers greatly impair its overall therapeutic efficacy. Herein, a series of water-soluble aggregation-induced emission luminogens (AIEgens) with triphenylamine as skeleton were synthesized and exhibited bright Near-infrared (NIR) emission and strong reactive oxygen species (ROS) generation. Through host-guest complexation between the multicharged triphenylamine units on AIEgens and cucurbit[10]uril (CB[10]) host molecule, supramolecular nanoassemblies were constructed and exhibited negligible phototoxicity to normal cells due to their limited oxygen contact. In contrast, the efficient release of AIEgens from nanoassemblies through competitive binding of overexpressed peptides in cancer cells with CB[10], enabled the full exploitation of the photosensitivity of AIEgens to produce highly efficient ROS, achieving selective ablation of cancer cells. Moreover, due to the restriction of intramolecular motion (RIM) upon anchored on organelle membranes through electrostatic interactions, the cationic AIEgens with weak fluorescence in physiological environment exhibited intense fluorescence emission, thus realizing imaging-guided PDT. This work may open up an avenue for the development of simple and feasible smart responsive nanomaterials for cancer treatment using supramolecular host-guest complexation strategy.

Supramolecular DNA nanogels through host-guest interaction for targeted drug delivery.

DNA hydrogels have been demonstrated with the advantages of good stability, easy modification, and extraordinary biocompatibility, which enables their great application prospects in biosensing, tissue engineering, and biomedicine. Based on the host-guest recognition properties of cucurbit[8]uril (CB[8]), we proposed a general method for constructing functional supramolecular DNA nanogels. Guest molecules have been conjugated into the DNA building units, which could be further crosslinked with CB[8] to construct supramolecular DNA nanogels. At the same time, the aptamer has also been modified into the hydrogel network to achieve cell targeting. These supramolecular DNA nanogels have been demonstrated with a controllable size and multiple stimuli responses, in addition to the excellent biocompatibility, stability and good targeting drug transport ability. Such a host-guest based strategy will provide a molecular library as a "toolbox" for the functionalization of DNA nanogels.

Cucurbit[7]uril-Based Supramolecular DNA Nanogel for Targeted Codelivery of Chemo/Photodynamic Drugs.

Nanodrug delivery systems for the delivery of combination therapeutics have shown their exceptionally potential clinical application by facilitating better synergistic anticancer effects. Herein, we developed a universal strategy to fabricate supramolecular DNA nanogels from DNA tetrahedron skeleton and cucurbit[7]uril-based host-guest interaction for codelivery the chemo and photodynamic therapy drugs. The constructed supramolecular DNA nanogels showed the size tunability, host-guest competition and DNA enzyme responsibility. The cell uptake and MTT experiments demonstrated that the nanogel has excellent biocompatibility and specificity, and achieved the enrichment and slow release of drug in cells. Finally, the combined chemo/photodynamic therapy was realized by coloading doxorubicin hydrochloride and methylene blue. It was proven to be a better stragety to promote apoptosis of cancer cells compared to single chemotherapy or photodynamic therapy. These results suggest that our proposed supramolecular nanogels have provided an effective nanoplatform for drug delivery in the combinational therapy for cancer.