Systemic tumour suppression via the preferential accumulation of erythrocyte-anchored chemokine-encapsulating nanoparticles in lung metastases

Zongmin Zhao, Anvay Ukidve, Vinu Krishnan, Alexandra Fehnel, Daniel C. Pan, Yongsheng Gao, Jayoung Kim, Michael A. Evans, Abhirup Mandal, Junling Guo, Vladimir R. Muzykantov, Samir Mitragotri

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Eliciting immune responses against primary tumours is hampered by their immunosuppressive microenvironment and by the greater inaccessibility of deeper intratumoural cells. However, metastatic tumour cells are exposed to highly perfused and immunoactive organs, such as the lungs. Here, by taking advantage of the preferential colocalization of intravenously administered erythrocytes with metastases in the lungs, we show that treatment with chemokine-encapsulating nanoparticles that are non-covalently anchored onto the surface of injected erythrocytes results in local and systemic tumour suppression in mouse models of lung metastasis. Such erythrocyte-anchored systemic immunotherapy led to the infiltration of effector immune cells into the lungs, in situ immunization without the need for exogenous antigens, inhibition of the progression of lung metastasis, and significantly extended animal survival and systemic immunity that suppressed the growth of distant tumours after rechallenge. Erythrocyte-mediated systemic immunotherapy may represent a general and potent strategy for cancer vaccination.

Original languageEnglish
Pages (from-to)441-454
Number of pages14
JournalNature Biomedical Engineering
Volume5
Issue number5
DOIs
StatePublished - May 2021

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