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Article

Indocyanine Green-Nexturastat A-PLGA Nanoparticles Combine Photothermal and Epigenetic Therapy for Melanoma

1
The Institute for Biomedical Sciences, The George Washington University, 2300 Eye Street NW, Room 561, Washington, DC 20037, USA
2
The George Washington Cancer Center, The George Washington University, 800 22nd St NW, Science and Engineering Hall, Suite 8000, Washington, DC 20052, USA
3
Center for Cancer and Immunology Research, Children’s National Health System, 111 Michigan Ave NW, Washington, DC 20010, USA
4
Department of Medicine, The George Washington University, 2150 Pennsylvania Avenue NW, Suite 8-416, Washington, DC 20037, USA
*
Author to whom correspondence should be addressed.
Nanomaterials 2020, 10(1), 161; https://doi.org/10.3390/nano10010161
Received: 8 December 2019 / Revised: 11 January 2020 / Accepted: 15 January 2020 / Published: 17 January 2020
(This article belongs to the Special Issue Immune Responses to Nanomaterials for Biomedical Applications)
In this study, we describe poly (lactic-co-glycolic) acid (PLGA)-based nanoparticles that combine photothermal therapy (PTT) with epigenetic therapy for melanoma. Specifically, we co-encapsulated indocyanine green (ICG), a PTT agent, and Nexturastat A (NextA), an epigenetic drug within PLGA nanoparticles (ICG-NextA-PLGA; INAPs). We hypothesized that combining PTT with epigenetic therapy elicits favorable cytotoxic and immunomodulatory responses that result in improved survival in melanoma-bearing mice. We utilized a nanoemulsion synthesis scheme to co-encapsulate ICG and NextA within stable and monodispersed INAPs. The INAPs exhibited concentration-dependent and near-infrared (NIR) laser power-dependent photothermal heating characteristics, and functioned as effective single-use agents for PTT of melanoma cells in vitro. The INAPs functioned as effective epigenetic therapy agents by inhibiting the expression of pan-histone deacetylase (HDAC) and HDAC6-specific activity in melanoma cells in vitro. When used for both PTT and epigenetic therapy in vitro, the INAPs increased the expression of co-stimulatory molecules and major histocompatibility complex (MHC) Class I in melanoma cells relative to controls. These advantages persisted in vivo in a syngeneic murine model of melanoma, where the combination therapy slowed tumor progression and improved median survival. These findings demonstrate the potential of INAPs as agents of PTT and epigenetic therapy for melanoma. View Full-Text
Keywords: PLGA nanoparticles; photothermal therapy; epigenetic therapy; melanoma; indocyanine green; HDAC inhibitors; Nexturastat A PLGA nanoparticles; photothermal therapy; epigenetic therapy; melanoma; indocyanine green; HDAC inhibitors; Nexturastat A
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MDPI and ACS Style

Ledezma, D.K.; Balakrishnan, P.B.; Cano-Mejia, J.; Sweeney, E.E.; Hadley, M.; Bollard, C.M.; Villagra, A.; Fernandes, R. Indocyanine Green-Nexturastat A-PLGA Nanoparticles Combine Photothermal and Epigenetic Therapy for Melanoma. Nanomaterials 2020, 10, 161. https://doi.org/10.3390/nano10010161

AMA Style

Ledezma DK, Balakrishnan PB, Cano-Mejia J, Sweeney EE, Hadley M, Bollard CM, Villagra A, Fernandes R. Indocyanine Green-Nexturastat A-PLGA Nanoparticles Combine Photothermal and Epigenetic Therapy for Melanoma. Nanomaterials. 2020; 10(1):161. https://doi.org/10.3390/nano10010161

Chicago/Turabian Style

Ledezma, Debbie K.; Balakrishnan, Preethi B.; Cano-Mejia, Juliana; Sweeney, Elizabeth E.; Hadley, Melissa; Bollard, Catherine M.; Villagra, Alejandro; Fernandes, Rohan. 2020. "Indocyanine Green-Nexturastat A-PLGA Nanoparticles Combine Photothermal and Epigenetic Therapy for Melanoma" Nanomaterials 10, no. 1: 161. https://doi.org/10.3390/nano10010161

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