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Sci Rep. 2017 Oct 23;7(1):13738. doi: 10.1038/s41598-017-14221-2.

A chloroquine-induced macrophage-preconditioning strategy for improved nanodelivery.

Author information

1
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, 77030, USA. wolfram.joy@mayo.edu.
2
Department of Transplantation, Mayo Clinic, Jacksonville, FL, 32224, USA. wolfram.joy@mayo.edu.
3
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, 77030, USA.
4
Applied Physics Graduate Program, Rice University, Houston, TX, 77005, USA.
5
Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, 10065, USA.
6
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, 77030, USA. mferrari@houstonmethodist.org.
7
Department of Medicine, Weill Cornell Medicine, Weill Cornell Medicine, New York, NY, 10065, USA. mferrari@houstonmethodist.org.

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.

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