Multifunctional injectable hydrogels for three-in-one cancer therapy: Preoperative remission via mild photothermal-enhanced supramolecular chemotherapy and prevention of postoperative recurrence and adhesion

• Injectable and multifunctional hydrogel for smart pre/postoperative cancer therapy. • “Three-in-one” therapeutic strategy for simultaneously handling tumor and complications. • Synergistic antitumor effect of supramolecular chemotherapy combining mild photothermal. • Multipronged design maximized biosafety of cancer therapy for clinical application. Traditional oncotherapy, involving surgical resection supplemented with systemic chemotherapy, is often accompanied by severe adverse-effects of cytotoxic drugs, a high risk of relapse, and also many surgery-induced complications. Here, a multifunctional hydrogel therapeutic platform integrating supramolecular chemotherapy and mild photothermal therapy is designed, for “three-in-one” colorectal cancer therapy, to achieve effective tumor remission before resection by local minimally invasive administration and also to prevent postoperative tumor recurrence and abdominal adhesion. The host–guest complex of oxaliplatin@cucurbit [7] uril (OxPt@CB [7] ) and gold nanoparticles (AuNPs) are incorporated into chitosan/oxidized-konjac glucomannan (CS/OKGM) matrixes to construct a supramolecular drug-loaded nanocomposite hydrogel (NCH), which possesses excellent syringeability and self-healing properties endowed by reversible Schiff-base linkages. Preoperatively, local administration of this dual-therapy hydrogel and the spermine-displacement release of OxPt from the OxPt@CB [7] complex in tumor microenvironment minimize the systemic toxicity of anticancer agents while markedly improving the therapeutic efficacy, which is further enhanced by the synergistic effect of mild photothermy and spermine consumption. After removing the major part of the tumors, supramolecular chemotherapy alone, without photothermal assistance, still exhibits a satisfactory inhibition for cancer recurrence. Meanwhile, the CS/OKGM hydrogel carrier itself is also shown to be an excellent barrier material for effectively preventing postoperative adhesion. This hydrogel-based local therapy may represent a novel paradigm, combined with conventional surgery management, for the more desired effect of tumor therapy and simultaneously handling tumor-associated complications.