Supramolecular Theranostic Nanomedicine for In Situ Self-Boosting Cancer Photochemotherapy

Although traditional nanomedicines have enhanced the therapeutic efficacy and improved the survival quality of cancer patients, random drug release and drug resistance are deep-rooted problems hindering their clinical application. A precise nanoplatform combing chemotherapy and photodynamic therapy (PDT) is developing as a new therapeutic strategy to overcome the above challenges. Herein, a novel supramolecular nanomedicine is ingeniously constructed for in situ self-boosting cancer photochemotherapy. Hydrophilic polyethylene glycol (PEG) chains or β-cyclodextrin (β-CD) hosts are first conjugated onto tetraphenyl porphyrin (TCPP) to improve the solubility of TCPP and decrease their π-π stacking interactions, guaranteeing a high-efficiency PDT. Then, two camptothecin (CPT) molecules are linked together via a reactive oxygen species (ROS)-responsive thioketal bond, which averts the premature burst release of CPT and realizes in situ drug release at the tumor site where PDT is performed, resulting in an enhanced chemotherapy. Benefiting from the collaboration of host-guest complexation between β-CD and CPT, multiple intermolecular hydrogen bonds of β-CD, π-π stacking interactions among CPT and TCPP as well as PEG shell protection, a prolonged blood circulation time, and a selective tumor accumulation are acquired, which facilitate the synergistic photochemotherapy and bring a pre-eminent antitumor response with a low systemic toxicity.