Journal
ACS NANO
Volume 13, Issue 2, Pages 1469-1478Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b07141
Keywords
adoptive T-cell therapy; intratumoral microenvironment; magnetic nanoclusters; pH sensitive; solid tumor
Categories
Funding
- National Natural Science Foundation of China [81571813, 21874011, 21372028, 21422502, 81302704, 21622608]
- National Key R&D Program of China [2017YFA0207900]
- Beijing Talents Fund [2015000021223ZK20]
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Although adoptive T-cell therapy has been successful in hematological malignancy treatment, its application in solid tumors remains a great challenge. Here, using a pH-sensitive benzoic-imine bond and inverse electron-demand Diels-Alder cycloaddition, we prepared magnetic nanoclusters (NCs) armed with responsive PD-1 antibody (aP), which could then bind onto effector T cells due to their PD-1 expression. After adoptive transfer, the magnetization and superparamagnetism of NCs enabled us to magnetically recruit effector T cells and aP simultaneously to tumor sites with MRI guidance. Owing to the acidic intratumoral microenvironment, the benzoic-imine bond then hydrolyzed, leading to the release of aP. The therapeutic effects of adoptive T cells and free aP could thus be spatiotemporally coupled. As a result, we achieved inhibition of tumor growth with few side effects, demonstrating the great promise of such a chemical approach for safe and high-performance adoptive T-cell therapy against solid tumors.
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