Journal
ADVANCED MATERIALS
Volume 31, Issue 10, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201802228
Keywords
checkpoint blockade; immunotherapy; nanoparticles; radiotherapy; tumor hypoxia relief
Categories
Funding
- National Basic Research Programs of China (973 Program) [2016YFA0201200]
- National Natural Science Foundation of China [51525203, 51761145041]
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions
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External radiotherapy is extensively used in clinic to destruct tumors by locally applied ionizing-radiation beams. However, the efficacy of radiotherapy is usually limited by tumor hypoxia-associated radiation resistance. Moreover, as a local treatment technique, radiotherapy can hardly control tumor metastases, the major cause of cancer death. Herein, core-shell nanoparticles based poly(lactic-co-glycolic) acid (PLGA) are fabricate, by encapsulating water-soluble catalase (Cat), an enzyme that can decompose H2O2 to generate O-2, inside the inner core, and loading hydrophobic imiquimod (R837), a Toll-like-receptor-7 agonist, within the PLGA shell. The formed PLGA-R837@Cat nanoparticles can greatly enhance radiotherapy efficacy by relieving the tumor hypoxia and modulating the immune-suppressive tumor microenvironment. The tumor-associated antigens generated postradiotherapy-induced immunogenic cell death in the presence of such R837-loaded adjuvant nanoparticles will induce strong antitumor immune responses, which together with cytotoxic T-lymphocyte associated protein 4 (CTLA-4) checkpoint blockade will be able to effectively inhibit tumor metastases by a strong abscopal effect. Moreover, a long term immunological memory effect to protect mice from tumor rechallenging is observed post such treatment. This work thus presents a unique nanomedicine approach as a next-generation radiotherapy strategy to enable synergistic whole-body therapeutic responses after local treatment, greatly promising for clinical translation.
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