Biodegradable 3D Injectable Amino Acid Hydrogels Delivering Immune Adjuvant for Enhancing Immunotherapy in Colon...

Area of Science:

• Biomaterials Science
• Immunology
• Cancer Therapy

Background:

• Toll-like receptor agonists (R837) show promise in cancer immunotherapy but can cause severe side effects.
• Subcutaneous injection of drug delivery systems may improve R837 efficacy and safety.
• Biodegradable hydrogel scaffolds offer controlled drug release and localized delivery.

Purpose of the Study:

• To develop a biodegradable 3D injectable hydrogel scaffold (R837@Gel) for controlled subcutaneous delivery of R837.
• To evaluate the efficacy of R837@Gel in enhancing T-cell responses and combination therapy with PD-1 inhibitors.
• To assess the safety profile and degradation characteristics of the amino acid hydrogel scaffold.

Main Methods:

• Construction of biodegradable 3D injectable amino acid hydrogels using Fmoc-Phe and Phe2 substrates via catalase effect.
• Encapsulation of R837 within the hydrogel scaffold to create R837@Gel for subcutaneous injection.
• Assessment of R837 release kinetics, CD4+ and CD8+ T-cell responses, scaffold degradation, and in vivo efficacy with PD-1 blockade.

Main Results:

• R837@Gel demonstrated controlled release of R837 and provided 3D support after subcutaneous injection.
• Significant enhancement of CD4+ and CD8+ T-cell responses was observed (p < 0.001).
• The hydrogel scaffold showed a favorable safety profile, successful degradation, and improved efficacy of PD-1 blockade.

Conclusions:

• Biodegradable 3D injectable amino acid hydrogels effectively control R837 release, enhancing antitumor immunotherapy and mitigating systemic toxicity.
• R837@Gel combined with immune checkpoint blockade represents a potent strategy for cancer immunotherapy.
• Subdermal implants offer a promising approach for reduced dosing frequency and improved patient compliance in cancer treatment.