Design of an Injectable Magnetic Hydrogel Based on the Tumor Microenvironment for Multimodal Synergistic Cancer Therapy

Conventional tumor chemotherapy is limited by its low therapeutic efficacy and side effects, which severely hold back its further application. Drug delivery systems (DDSs) based on nanomaterials have attracted wide interest in cancer treatment; especially, the system can realize efficient synergistic therapies. Here, we designed a smart hydrogel drug delivery system with multiple responses to enhance the tumor treatment effect. By cross-linking oxidized hydroxypropyl cellulose with carboxymethyl chitosan, an injectable hydrogel was obtained, into which artesunate (ART), ferroferric oxide (Fe3O4) nanoparticles, and black phosphorus nanosheets (BPs) were preloaded. This DDS has multiple functions including magnetic targeting, pH sensitivity, chemodynamic therapy, and photothermal response. This nanoparticle-composited hydrogel not only preserved excellent rheological properties but also allowed for an accurate stable drug release at tumor sites and synergistic effects of multiple therapies. The in vitro and in vivo experiments revealed that this DDS could efficiently eliminate the HepG2 tumor with good biocompatibility. Taken together, this study clarifies the possible antitumor mechanism of this ART-loaded nanoparticle-composited hydrogel and provides a new strategy for synergistic photothermal- chemo-chemodynamic therapy.

Automated summary

Conventional tumor chemotherapy is limited by low efficacy and side effects. Nanomaterial-based drug delivery systems have gained interest for cancer treatment, especially for efficient synergistic therapies. In this study, a smart hydrogel drug delivery system was designed with multiple responses to enhance tumor treatment. The system showed excellent rheological properties, accurate stable drug release at tumor sites, and synergistic effects of multiple therapies. In vitro and in vivo experiments demonstrated efficient tumor elimination and good biocompatibility. This study clarifies the antitumor mechanism and provides a new strategy for synergistic photothermal- chemo-chemodynamic therapy.