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In Situ Formed Nanocomposite Hydrogel Improve Local Delivery of Antiangiogenic Agents and Immune Checkpoint Inhibitor
Jing Li1, Cuixia Zheng2, Lei Zhang3
1Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 191599, China.
Abstract:
Immune checkpoint blockade targeting the programmed cell death protein-1 (PD-1)/ligand (PD-L1) axis has emerged as a promising therapeutic strategy for cervical carcinoma. However, its clinical application remains limited by the immunosuppressive tumor microenvironment (TME) and poor targeting efficiency, particularly in solid tumors. To address these challenges, a nanocomposite hydrogel system (Apa/BPNPs@Gel) is developed by encapsulating PD-L1 inhibitor BMS202 nanoparticles coated with polyvinyl alcohol (BPNPs) into a polyvinyl alcohol/alginate hybrid hydrogel. This in situ formed hydrogel exhibits favorable biocompatibility and reactive oxygen species-dependent sequential drug release. Initially, the antiangiogenic agent apatinib (Apa) is released to alleviate tumor hypoxia through vascular normalization and enhance PD-L1 suppression, priming the TME for subsequent anti-PD(L)1 therapy. The hydrogel framework extends the residence time of BMS202 (a skeleton component), improving therapeutic efficacy. Notably, in preclinical cervical carcinoma models, Apa/BPNPs@Gel mediated combination therapy significantly inhibited tumor growth and prolonged survival by activating tumor-suppressed CD8+ T cells. Hence, this locally administrable hydrogel offers a versatile platform to modulate the immunosuppressive TME and enhance immunotherapeutic outcomes.
Insights
A novel hydrogel system delivers apatinib and a PD-L1 inhibitor to combat cervical cancer. This combination therapy effectively suppresses the immunosuppressive tumor microenvironment, inhibiting tumor growth and enhancing survival by activating CD8+ T cells.
Area of Science:
- Oncology
- Immunotherapy
- Biomaterials
Background:
- Immune checkpoint inhibitors targeting the programmed cell death protein-1 (PD-1)/ligand (PD-L1) axis show promise for cervical carcinoma.
- Clinical efficacy is limited by the immunosuppressive tumor microenvironment (TME) and poor targeting efficiency in solid tumors.
Purpose of the Study:
- To develop a nanocomposite hydrogel system (Apa/BPNPs@Gel) for localized delivery of an anti-angiogenic agent (apatinib) and a PD-L1 inhibitor (BMS202).
- To evaluate the efficacy of this combination therapy in preclinical cervical carcinoma models by modulating the TME and enhancing anti-PD(L)1 therapy.
Main Methods:
- Fabrication of a hybrid hydrogel encapsulating apatinib and BMS202-loaded nanoparticles.
- In situ hydrogel formation with biocompatibility and reactive oxygen species-dependent sequential drug release.
- Assessment of combination therapy effects on tumor growth, survival, and T cell activation in cervical cancer models.
Main Results:
- The Apa/BPNPs@Gel system demonstrated biocompatibility and controlled drug release.
- Sequential release of apatinib alleviated tumor hypoxia and PD-L1 expression, priming the TME.
- Combination therapy significantly inhibited tumor growth and prolonged survival by activating tumor-suppressed CD8+ T cells.
Conclusions:
- The locally administrable hydrogel platform effectively modulates the immunosuppressive TME in cervical cancer.
- This approach enhances immunotherapeutic outcomes by combining anti-angiogenesis and PD-L1 blockade.
- The developed hydrogel system offers a versatile strategy for improving cancer immunotherapy.
