Bioresponsive Self‐Reinforcing Sericin/Silk Fibroin Hydrogel for Relieving the Immune‐Related Adverse Events in Tumor Immunotherapy

Abstract

Despite the immense potential of immune checkpoint blockade (ICB) therapy in tumor treatment, its widespread clinical application is currently limited by unsatisfactory curative effect and off‐target adverse effect. Herein, an injectable sericin (SS)/silk fibroin (SF) recombinant hydrogel, termed SF‐SS‐SMC hydrogel, is developed to enable local delivery of anti‐CD47 antibody (α CD47). The hydrogel displays self‐reinforcement in high H2O2 concentration of tumor microenvironment (TME), as the SS/Fe2+ supramolecular nanocomplex (SS‐SMC) inside the hydrogel converts H2O2 to reactive oxygen species (ROS), further triggering additional crosslinking among the SF polymers. Therefore, the SF‐SS‐SMC hydrogel has an in vivo retention time longer than 21 days and acts as a reservoir for the long‐term sustained release of α CD47. More importantly, the SF‐SS‐SMC hydrogel itself efficiently regulates the remodeling of a protumor immunosuppressive TME to an antitumoral TME through switching of tumor‐associated macrophages from an anti‐inflammatory M2 phenotype to a proinflammatory M1 phenotype without additional drugs. Based on the combined effect of sustained α CD47 release and TME reprogramming, the SF‐SS‐SMC hydrogel has satisfactory immunotherapeutic effects in the treatment of local, abscopal, remitting, and metastatic tumors. Further advantages, including low cost of production, simple fabrication, and ease of use, make it promising for commercial mass production.

Glutathione-Responsive and Hydrogen Sulfide Self-Generating Nanocages Based on Self-Weaving Technology To Optimize Cancer Immunotherapy

“…SF is a commonly used natural polymer for the fabrication of micro/nanoparticles, hydrogels, sponges, and membranes. − Among these related studies, the preparation often involves the secondary structure transformation of SF from a random coil to an α-helix and β-sheet induced by desolvation, sonication, etc. This restructuring process is characterized by two distinct processes: stretching and alignment of SF molecular chains. − Stretching refers to break the original unstable structure to generate energy for a change in the molecular aggregation state .…”

Advances in Hydrogels of Drug Delivery Systems for Local Treatment of Brain Tumors

“…Implantable hydrogels serve not only to deliver chemotherapy drugs directly to the tumor but also to monitor the tumor's response in real time [47,48]. This could enable the adjustment of drug dosage based on the tumor's characteristics, thus optimizing treatment and minimizing side effects [20]. This approach to personalized medicine holds the potential to transform the therapy of brain tumors.…”

“…This paper summarizes the application of hydrogels in drug delivery systems and intelligent drug release control as shown in Figure 1. [18][19][20][21]. This article mainly summarizes the different drug delivery systems of hydrogels in the treatment of brain tumors, such as injection, spray, and implantation.…”

Advances in Hydrogels of Drug Delivery Systems for the Local Treatment of Brain Tumors

“…By summarizing the materials, characteristics, and application methods of hydrogels, they are categorized into injectable hydrogels, sprayable hydrogels, and implantable hydrogels [ 27 , 28 , 29 , 30 ]. Additionally, this article summarizes the specific applications of smart hydrogels in the treatment of brain tumors, including temperature- and pH-responsive hydrogels, photoresponsive hydrogels, and magnetic-responsive hydrogels [ 31 , 32 , 33 , 34 ]. Due to the rich water content and soft texture of brain tissue, hydrogels exhibit excellent biocompatibility and are more suitable for the unique environment of the brain [ 15 ].…”