Journal
ADVANCED MATERIALS
Volume 34, Issue 3, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202106520
Keywords
IDO1 inhibition; metabolic tumor microenvironment modulation; reinforced radiotherapy; tumor acidity neutralization
Categories
Funding
- National Natural Science Foundation of China [51802209, 22077093, 52032008]
- Ministry of Science and Technology (MOST) of China [2016YFA0201200]
- Natural Science Foundation of Jiangsu Province [BK20180848]
- Jiangsu Social Development Project [BE2019658]
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- 111 Program from the Ministry of Education of China
Ask authors/readers for more resources
The pH-responsive nanomedicine prepared in this study has shown promising results in enhancing the therapeutic efficacy of radiotherapy against tumors by neutralizing tumor acidity and inhibiting IDO1, resulting in robust antitumor immunity and suppression of tumor metastasis and recurrence.
Radiotherapy is widely exploited for the treatment of a large range of cancers in clinic, but its therapeutic effectiveness is seriously crippled by the tumor immunosuppression, mainly driven by the altered metabolism of cancer cells. Here, a pH-responsive nanomedicine is prepared by coating calcium carbonate (CaCO3) nanoparticles with 4-phenylimidazole (4PI), an inhibitor against indoleamine 2,3-dioxygenase 1 (IDO-1), together with zinc ions via the coordination reaction, aiming at reinforcing the treatment outcome of radiotherapy. The obtained pH-responsive nanomedicine, coined as acidity-IDO1-modulation nanoparticles (AIM NPs), is able to instantly neutralize protons, and release 4PI to suppress the IDO1-mediated production of kynurenine (Kyn) upon tumor accumulation. As a result, treatment with AIM NPs can remarkably enhance the therapeutic efficacy of radiotherapy against both murine CT26 and 4T1 tumors by eliciting potent antitumor immunity. Furthermore, it is shown that such combination treatment can effectively suppress the growth of untreated distant tumors via the abscopal effect, and result in immune memory responses to reject rechallenged tumors. This work highlights a novel strategy of simultaneous tumor acidity neutralization and IDO1 inhibition to potentiate radiotherapy, with great promises to suppress tumor metastasis and recurrence by eliciting robust antitumor immunity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available