A chloroquine-induced macrophage-preconditioning strategy for improved nanodelivery

Joy Wolfram, Sara Nizzero, Haoran Liu, Feng Li, Guodong Zhang, Zheng Li, Haifa Shen, Elvin Blanco, Mauro Ferrari

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Site-specific localization is critical for improving the therapeutic efficacy and safety of drugs. Nanoparticles have emerged as promising tools for localized drug delivery. However, over 90% of systemically injected nanocarriers typically accumulate in the liver and spleen due to resident macrophages that form the mononuclear phagocyte system. In this study, the clinically approved antimalarial agent chloroquine was shown to reduce nanoparticle uptake in macrophages by suppressing endocytosis. Pretreatment of mice with a clinically relevant dose of chloroquine substantially decreased the accumulation of liposomes and silicon particles in the mononuclear phagocyte system and improved tumoritropic and organotropic delivery. The novel use of chloroquine as a macrophage-preconditioning agent presents a straightforward approach for addressing a major barrier in nanomedicine. Moreover, this priming strategy has broad applicability for improving the biodistribution and performance of particulate delivery systems. Ultimately, this study defines a paradigm for the combined use of macrophage-modulating agents with nanotherapeutics for improved site-specific delivery.

Original languageEnglish (US)
Article number13738
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

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    Wolfram, J., Nizzero, S., Liu, H., Li, F., Zhang, G., Li, Z., Shen, H., Blanco, E., & Ferrari, M. (2017). A chloroquine-induced macrophage-preconditioning strategy for improved nanodelivery. Scientific Reports, 7(1), [13738]. https://doi.org/10.1038/s41598-017-14221-2