Fluorinated Cyclodextrin Supramolecular Nanoassembly Enables Oxygen-Enriched and Targeted Photodynamic Therapy

Photodynamic therapy has become a promising treatment modality against many diseases, but its dilemma―the intrinsic hypoxia of solid tumors and the high oxygen dependence for generation of cytotoxic species―has seriously hampered its practical translation. Herein a binary supramolecular nanocarrier, which is composed of fluorocarbon chain-appended β-cyclodextrin as an oxygen carrier and adamantane-grafted hyaluronic acid as a cell-targeting agent, can deliver different types of photosensitizers by multiple noncovalent interactions. Superior to the alkylated counterpart, the fluorinated amphiphilic β-cyclodextrin can spontaneously form a nanoparticulate assembly and exhibit high oxygen-enrichment performance. The obtained nanoassembly can alleviate hypoxia in the tumor microenvironment and enhance the efficacy of photodynamic therapy. Remarkable phototoxicity and minimal dark toxicity are observed in the cancer cells, and meanwhile, preferential accumulation and significant cancer ablation are realized in the tumor-bearing mice. To be envisioned, this supramolecular assembly capable of efficiently carrying oxygen can be explored as a universal platform for precise phototherapeutics.