Genetically Engineered Light-Responsive In Situ Hydrogels for Immunomodulation and Multimodal Therapy in Metastatic...

Area of Science:

• Biomaterials Science
• Cancer Biology
• Drug Delivery

Background:

• Triple-negative breast cancer (TNBC) is aggressive with poor prognosis and limited treatment options.
• Conventional therapies for TNBC face challenges like low efficacy, side effects, and recurrence.
• There is a need for innovative strategies to improve TNBC treatment outcomes.

Purpose of the Study:

• To develop a novel tri-block chimeric protein hydrogel (cSELPs) for treating late-stage and metastatic TNBC.
• To integrate multiple functional motifs for enhanced therapeutic properties.
• To evaluate the efficacy and biocompatibility of the cSELP hydrogel system.

Main Methods:

• De novo design of cysteine-tagged silk-elastin-like proteins (cSELPs) with specific functional motifs.
• Formation of in situ hydrogels capable of responsive drug and immunotherapy release.
• Assessment of tumor microenvironment remodeling, immunogenic cell death, and immune activation.
• Evaluation of therapeutic efficacy against primary and metastatic TNBC in vivo.
• Analysis of biocompatibility and long-term safety.

Main Results:

• cSELP hydrogels demonstrated in situ gelation and controlled release of doxorubicin and anti-PD-L1.
• The system effectively remodeled the tumor microenvironment, converting "cold" tumors to "hot" tumors.
• Significant therapeutic efficacy was observed against both primary and metastatic TNBC.
• Excellent biocompatibility and long-term safety were maintained.

Conclusions:

• The cSELP hydrogel platform offers a promising strategy for multimodal treatment of TNBC.
• This innovative approach reshapes the tumor microenvironment and enhances therapeutic outcomes.
• The developed protein material platform shows potential for clinical translation in TNBC treatment.