The chimeric antigen receptor-T cells (CAR-T) therapy, as a novel personalized immunotherapy, has shown prominent clinical efficacy in the treatment of B-cell malignancies. However, the progress in solid tumors was hindered by multiple elements in the tumor immunosuppressive microenvironment. In this study, an injectable and photocurable Gelatin Methacryloyl (GelMA) hydrogel was applied to be a depot of CAR-T cells, thus forming an injectable CAR-T Gelatin Methacryloyl hydrogels Delivery (i-GMD) system. According to our results, CAR-T cells in this system could be normally amplified, sustained released, and play an anti-tumor role in vitro. When compared with local or intravenously injection of CAR-T solution, injection of i-GMD matrix around tumor demonstrated enhanced anti-tumor effect and markedly extended survival of mice. Our research outcomes indicated that this therapeutic strategy might hopefully provide a treatment for patients with unresectable tumors.

2022-11-30

Biomaterials

West China Hospital, Sichuan University

Currently, activatable photodynamic therapy (PDT) that is precisely regulated by endogenous or exogenous stimuli to selectively produce cytotoxic reactive oxygen species at the tumor site is urgently in demand. Herein, we fabricated a dual-activatable PDT nanosystem regulated by the redox tumor microenvironment and near-infrared (NIR) light-induced photothermal therapy (PTT). In this study, photosensitizer chlorin e6 (Ce6) was conjugated to hyaluronic acid (HA) via a diselenide bond to form an amphiphilic polymer (HSeC) for loading PTT agent IR780 to produce HSeC/IR nanoparticles (NPs). The photoactivity of Ce6 for PDT was “double-locked” by the aggregation-caused quenching (ACQ) effect and the fluorescence resonance energy transfer (FRET) from Ce6 to IR780 during blood circulation. After selective accumulation into tumors, HSeC/IR NPs were subsequently dissociated due to the “double-key”, which included diselenide bond dissociation under high redox conditions and IR780 degradation upon NIR laser irradiation, resulting in recovering Ce6. In vitro studies indicated that Ce6 photoactivity in HSeC/IR NPs was significantly suppressed when compared with free Ce6 or in HSeC NPs. Moreover, BALB/c mice treated with HSeC/IR NPs displayed distinctly alleviated skin damage during PDT. Synergetic cascaded PTT-PDT with superior tumor suppression was observed in SCC7 tumor-bearing mice. Therefore, the study findings could provide a promising treatment strategy for PTT-facilitated PDT with high antitumor efficacies and reduced skin phototoxicity levels.

2022-09-30

Biomaterials

West China Hospital, Sichuan University