Dual-Crosslinked Dynamic Hydrogel Incorporating {Mo154} with pH and NIR Responsiveness for Chemo-Photothermal Therapy

Polyoxometalates are an emerging class of molecular clusters, with well-defined structures and chemical compositions that are produced through simple, low-cost, and highly reproducible methods. In particular, the wheel-shaped cluster {Mo-154} is a promising photothermal agent due to its intervalence charge transfer transitions. However, its toxicity hinders its systemic administration, being the development of a localized delivery system still incipient. Herein, an injectable and self-healing hydrogel of easy preparation and administration is developed, incorporating both {Mo-154} and doxorubicin for synergistic photothermal and chemotherapy applications. The hydrogel is composed of benzylaldehyde functionalized polyethylene glycol, poly(N-isopropylacrylamide) functionalized chitosan and {Mo-154}. The gelation occurs within 60 s at room temperature, and the dual crosslinking by Schiff base and electrostatic interactions generates a dynamic network, which enables self-healing after injection. Moreover, the hydrogel delivers chemotherapeutic drugs, with a release triggered by dual near infra-red (NIR) radiation and pH changes. This stimuli-responsive release system along with the photothermal conversion ability of the hydrogel allows the simultaneous combination of photothermal and chemotherapy. This synergic system efficiently ablates the cancer tumor in vivo with no systemic toxicity. Overall, this work paves the way for the development of novel {Mo-154}-based systems, incorporated in self-healing and injectable hydrogels for dual chemo-photothermal therapy.

Automated summary

Polyoxometalates, specifically the {Mo-154} wheel-shaped cluster, show promise as photothermal agents, but toxicity limits systemic administration. This study introduces an injectable and self-healing hydrogel incorporating {Mo-154} and doxorubicin for synergistic photothermal and chemotherapy applications. The hydrogel's dual crosslinking allows for self-healing after injection, while a stimuli-responsive release system enables precise delivery of chemotherapeutic drugs triggered by dual near infrared radiation and pH changes for effective cancer tumor ablation with no systemic toxicity.