NIR irradiation-controlled drug release utilizing injectable hydrogels containing gold-labeled liposomes for the treatment of melanoma cancer

Abstract Drug-based chemotherapy is associated with serious side effects. We developed a chemotherapeutic system comprising a chitosan hydrogel (CH-HG) containing gold cluster-labeled liposomal doxorubicin (DOX) (CH-HG-GLDOX) as an injectable drug depot system. CH-HG-GLDOX can be directly injected into tumor tissue without a surgical procedure, allowing this system to act as a reservoir for liposomal DOX. CH-HG-GLDOX enhanced the retention time of DOX in tumor tissue and controlled its release in response to near-infrared (NIR) irradiation, resulting in significant inhibition of tumor growth and reduced DOX-related toxicity. The combined effect of CH-HG-GLDOX and poly (D,L-lactide-co-glycolic acid) nanoparticle-based vaccines increased cytotoxic CD8+ T cell immunity, leading to enhanced synergistic therapeutic efficacy. CH-HG-GLDOX provides an advanced therapeutic approach for local drug delivery and controlled release of DOX, resulting in reduced toxicity. Here, we suggest a combination strategy for chemo- and immunotherapies, as well as in nanomedicine applications. Statement of Significance We developed an injectable hydrogel containing gold cluster-labeled liposomes for sustained drug release at the tumor site. Moreover, we demonstrated the combined therapeutic efficacy of a hydrogel system and a nanoparticle-based immunotherapeutic vaccine for melanoma cancer. Thus, we show a potential combination approach for chemo- and immunotherapies for cancer treatment.