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Research Article

PLGA nanodepots co-encapsulating prostratin and anti-CD25 enhance primary natural killer cell antiviral and antitumor function

Elizabeth E. Sweeney1,§, Preethi B. Balakrishnan1,§, Allison B. Powell2, Allan Bowen1, Indra Sarabia3, Rachel A. Burga1, R. Brad Jones4, Alberto Bosque3, C. Russell Y. Cruz1,2, Rohan Fernandes1,5( )
The George Washington Cancer Center, The George Washington University, Washington, DC 20052, USA
Center for Cancer and Immunology Research, Children’s National Health System, Washington, DC 20010, USA
Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington, DC 20052, USA
Infectious Disease Division, Weill Cornell Medical College, New York, NY 10065, USA
Department of Medicine, The George Washington University, Washington, DC 20052, USA

§ Elizabeth E. Sweeney and Preethi B. Balakrishnan contributed equally to this work.

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Abstract

Natural killer (NK) cells are attractive effector cells of the innate immune system against human immunodeficiency virus (HIV) and cancer. However, NK cell therapies are limited by the fact that target cells evade NK cells, for example, in latent reservoirs (in HIV) or through upregulation of inhibitory signals (in cancer). To address this limitation, we describe a biodegradable nanoparticle-based "priming" approach to enhance the cytotoxic efficacy of peripheral blood mononuclear cell-derived NK cells. We present poly(lactic-co-glycolic acid) (PLGA) nanodepots (NDs) that co-encapsulate prostratin, a latency-reversing agent, and anti-CD25 (aCD25), a cell surface binding antibody, to enhance primary NK cell function against HIV and cancer. We utilize a nanoemulsion synthesis scheme to encapsulate both prostratin and aCD25 within the PLGA NDs (termed Pro-aCD25-NDs). Physicochemical characterization studies of the NDs demonstrated that our synthesis scheme resulted in stable and monodisperse Pro-aCD25-NDs. The NDs successfully released both active prostratin and anti-CD25, and with controllable release kinetics. When Pro-aCD25-NDs were administered in an in vitro model of latent HIV and acute T cell leukemia using J-Lat 10.6 cells, the NDs were observed to prime J-Lat cells resulting in significantly increased NK cell-mediated cytotoxicity compared to free prostratin plus anti-CD25, and other controls. These findings demonstrate the feasibility of using our Pro-aCD25-NDs to prime target cells for enhancing the cytotoxicity of NK cells as antiviral or antitumor agents.

Keywords

poly(lactic-co-glycolic acid) (PLGA) nanodepotsnatural killer (NK) cellshuman immunodeficiency virus (HIV)cancerlatency-reversing agentantibody

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Nano Research
Volume 13 Issue 3,
March 2020
Pages 736-744
DOI: 10.1007/s12274-020-2684-1
Cite this article:
Sweeney EE, Balakrishnan PB, Powell AB, et al. PLGA nanodepots co-encapsulating prostratin and anti-CD25 enhance primary natural killer cell antiviral and antitumor function. Nano Research, 2020, 13(3): 736-744. https://doi.org/10.1007/s12274-020-2684-1
Topics:
Antibodies Cell death Cell membranes CellsViruses

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Received: 18 September 2019
Revised: 07 January 2020
Accepted: 17 January 2020
Published: 21 February 2020
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020
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