Injectable Zwitterionic Physical Hydrogel with Enhanced Chemodynamic Therapy and Tumor Microenvironment Remodeling Properties for Synergistic Anticancer Therapy

Abstract

Surgical resection is the first-line therapy for breast cancer. However, residual tumor cells and the highly immunosuppressive tumor microenvironment (TME) continue to have a serious impact on tumor recurrence and metastasis postresection. Implantation of an in situ hydrogel system postresection has shown to be an effective treatment with great clinical potential. Herein, an injectable zwitterionic hydrogel system was developed for local drug delivery with enhanced immune activation and prevention of tumor recurrence. Driven by electrostatic interactions, poly-(sulfobetaine methacrylate) (PSBMA) self-assembles into a hydrogel in saline, achieving low protein adsorption and tunable biodegradability. The chemotherapy drug doxorubicin (DOX) was loaded into copper peroxide nanoparticles (CuO 2 /DOX), which were coated with macrophage membranes to form tumor-targeting nanoparticles (M/CuO 2 /DOX). Next, M/CuO 2 /DOX and the stimulator of interferon genes (STING) agonist 2′,3′-cGAMP were coloaded into PSBMA hydrogel (Gel@M/CuO 2 /DOX/STING). The hydrophilic STING agonist was first released by diffusion from hydrogel to activate the STING pathway and upregulate interferon (IFN) signaling related genes, remodeling the immunosuppressive TME. Then, M/CuO 2 /DOX targeted the residual tumor cells, combining with DOX-induced DNA damage, immunogenic tumor cell death, and copper death. Hence, this work combines chemodynamic therapy with STING pathway activation in TME, encouraging residual tumor cell death, promoting the maturation of dendritic cells, enhancing tumor-specific CD8 + T cell infiltration, and preventing postoperative recurrence and metastasis.

NIR-Mediated Pyroelectric Catalysis for Sustained ROS/RNS Generation and Advanced Cancer Therapy In Vivo via Injectable Hydrogel

“…Injectable hydrogels have the advantages of controllable degradability, excellent biocompatibility, and biomimetic profiles . In this study, the degradation curves of BAG hydrogels were tested in water, PBS, and a cell medium of Roswell Park Memorial Institute (RPMI-1640) within 14 days (Figure C), and corresponding data indicated that BAG was stable in a hydrogel state for 14 days in vitro, which met the requirements of controllable degradation and sustained drug release for in situ tumor therapy.…”

Recent progress in biomaterials-driven ferroptosis for cancer therapy

“…This double-sensitive hydrogel is self-assembled in saline water by polysulfonamide acrylate (PSBMA) driven by electrostatic interactions and has low protein adsorption and adjustable biodegradability. 143 Based on these advantages, hydrogels have been widely used in cancer treatment in recent years. Therefore, the following application of hydrogels based on ferroptosis in cancer treatment will be discussed in detail.…”

Hydrogels as local depots for on-demand therapeutic delivery: potential therapeutic approaches for tumor metastasis

“…Injectable in situ formed hydrogel is a suitable local drug delivery alternative post-surgical cavity implant for the prevention of cancer recurrence and distant metastasis. 96–99 Overall, hydrogel-based local delivery of chemotherapy can combat tumor metastasis by eradicating tumor cells, 100 remodeling the tumor microenvironment, 101,102 such as blocking the function of cancer-associated adipocytes to inhibit adipocyte-stimulated tumor cell proliferation, cell migration, and angiogenesis, 66 and inducing immunogenic cell death 103 (Fig. 2).…”