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Issue 28, 2020
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A tumor acidity activatable and Ca2+-assisted immuno-nanoagent enhances breast cancer therapy and suppresses cancer recurrence

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Abstract

Breast cancer recurrence is the greatest contributor to patient death. As the immune system has a long-term immune memory effect, immunotherapy has great potential for preventing cancer recurrence. However, cancer immunotherapy is often limited due to T cell activation being blocked by insufficient tumor immunogenicity and the complex immunosuppressive tumor microenvironment. Here we show a tumor acidity activatable and Ca2+-assisted immuno-nanoagent to synergistically promote T cell activation and enhance cancer immunotherapy. When the immuno-nanoagent reaches the acidic tumor microenvironment, the CaCO3 matrix disintegrates to release immune stimulants (CpG ODNs and IDOi) and Ca2+. CpG ODNs are responsible for triggering dendritic cell maturation to increase the immunogenicity for activation of T cells. And IDOi can inhibit the oxidative catabolism of tryptophan to kynurenine for preventing T-cell anergy and apoptosis. Due to the complexity of the immunosuppressive microenvironment, it is difficult to restore T cell activation by inhibiting only one pathway. Fortunately, the released Ca2+ can promote the activation and proliferation of T cells with the support of the immune stimulants. In vivo experiments demonstrate that our Ca2+-assisted immuno-nanoagent can significantly suppress tumor progression and protect mice from tumor rechallenge due to the long-term memory effect. This immunotherapeutic strategy may provide more possibilities for clinical applications such as treating cancer and preventing relapse.

Graphical abstract: A tumor acidity activatable and Ca2+-assisted immuno-nanoagent enhances breast cancer therapy and suppresses cancer recurrence

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Supplementary files

Article information


Submitted
16 Jan 2020
Accepted
22 Jun 2020
First published
29 Jun 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 7429-7437
Article type
Edge Article

A tumor acidity activatable and Ca2+-assisted immuno-nanoagent enhances breast cancer therapy and suppresses cancer recurrence

Y. Li, S. Gong, W. Pan, Y. Chen, B. Liu, N. Li and B. Tang, Chem. Sci., 2020, 11, 7429 DOI: 10.1039/D0SC00293C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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