Heat-Confined Tumor-Docking Reversible Thermogel Potentiates Systemic Antitumor Immune Response During Near-Infrared Photothermal Ablation in Triple-Negative Breast Cancer.

Autor: Revuri V; Department of Green Bioengineering, Korea National University of Transportation, Chungju, 27469, Republic of Korea., Rajendrakumar SK; Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea., Park MS; Department of Hematology-Oncology, Chonnam National University Medical School, Gwangju, 61469, South Korea., Mohapatra A; Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea., Uthaman S; Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea., Mondal J; Department of Green Bioengineering, Korea National University of Transportation, Chungju, 27469, Republic of Korea., Bae WK; Department of Hematology-Oncology, Chonnam National University Medical School, Gwangju, 61469, South Korea., Park IK; Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju, 61469, Republic of Korea., Lee YK; Department of Green Bioengineering, Korea National University of Transportation, Chungju, 27469, Republic of Korea.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2021 Nov; Vol. 10 (21), pp. e2100907. Date of Electronic Publication: 2021 Sep 20.
DOI: 10.1002/adhm.202100907
Abstrakt: Triple-negative breast cancer (TNBC) features immunologically "cold" tumor microenvironments with limited cytotoxic T lymphocyte (CTL) infiltration. Although ablation therapies have demonstrated modulation of "cold" TNBC tumors to inflamed "hot" tumors, recruitment of myeloid derived suppressor cells (MDSCs) at the tumors post ablation therapies prevents the infiltration of CTLs and challenge the antitumor potentials of T-cell therapies. Here, a thermal ablation immunotherapy strategy is developed to prevent the immune suppressive effects of MDSCs during photothermal ablation and induce a durable systemic antitumor immunity to eradicate TNBC tumors. An injectable pluronic F127/hyaluronic acid (HA)-based hydrogel embedded with manganese dioxide (BM) nanoparticles and TLR7 agonist resiquimod (R848) (BAGEL-R848), is synthesized to induce in situ laser-assisted gelation of the hydrogel and achieve desired ablation temperatures at a low laser-exposure time. Upon 808-nm laser irradiation, a significant reduction in the tumor burden is observed in BAGEL-R848-injected 4T1 tumor-bearing mice. The ablation induced immunogenic cell death and sustained release of R848 from BAGEL-R848 promotes dendritic cell maturation and reduced MDSCs localization in tumors. In addition, inflammatory M1 macrophages and CD8+IFN+ CTL are enriched in distant tumors in bilateral 4T1 tumor model, preventing metastatic tumor growth and signifying the potential of BAGEL-R848 to treat TNBC.
(© 2021 Wiley-VCH GmbH.)
Databáze: MEDLINE
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