Journal
BIOMATERIALS
Volume 280, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.121272
Keywords
Single atom nanozyme; Injectable hydrogel; Adhesive hydrogel; Immunomodulation; Immunotherapy
Funding
- Key-Area Research and Development Program of Guang Dong Province [2019B010941002]
- NSFC [82072071, 82072073]
- Shenzhen Funds of the Central Government [2021SZVUP123]
- Fundamental Research Funds for the Central Universities [2682020ZT79, 2682021CX109, 2682021ZTPY019]
- Sichuan Science and Technology Program [2020YJ0009]
- Collaborative Innovation Center of Suzhou Nano Science Technology
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- 111 Project
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This study developed a bioadhesive injectable hydrogel for localized immune modulation and catalytic immunotherapy in cancer treatment. The hydrogel containing a nanozyme and immune adjuvant effectively targeted the tumor microenvironment while limiting systemic exposure and enhancing therapeutic efficacy.
Immunotherapy is a powerful way to treat cancer, however, systemic treatment-associated adverse effects remain a major concern. In this study, a bioadhesive injectable hydrogel is developed to provide localized immune niches for tumor microenvironment immunomodulation and cancer catalytic immunotherapy. First, a phenolic single atom nanozyme (SAN) was developed by in situ synthesis of Pd single atom on catechol-grafted carbon-quantum-dot (DA-CQD@Pd) templates. Then, the bioadhesive injectable hydrogel consisting of DACQD@Pd SAN and immune adjuvant CpGODN was formed through SAN-catalyzed free-radical polymerization. The SAN exhibited peroxidase-like activity to generate ROS and kill tumor cells through catalytic therapy. The hydrogel locally released CpGODN in a sustained manner, which limited the risk of systemic exposure, reducing the impact of CpGODN toxicity, and protecting CpGODN from degradation. The bioadhesive hydrogel immobilized around solid tumor to provide an immune response site after injection. When combined it with the administration of immune checkpoint inhibitor anti-PD-L1, the hydrogel realized localized immunomodulation, maximized therapeutic efficacy and prevents tumor metastasis via a catalytic immunotherapy.
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