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Department of Medicine, The George Washington University, 2300 I Street NW, Washington, DC 20037, USA

The George Washington Cancer Center, The George Washington University, Science & Engineering Hall, Ste 8300, Washington, DC 20052, USA

‡Authors contributed equally

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Carissa S Holmberg^‡

https://orcid.org/0000-0001-5577-9910

The Institute for Biomedical Sciences, The George Washington University, 2300 I Street NW, Ross Hall, Room 561, Washington, DC 20037, USA

Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, 2300 I Street NW, Washington, DC 20037, USA

‡Authors contributed equally

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Debbie K Ledezma

https://orcid.org/0000-0001-7922-3773

Department of Medicine, The George Washington University, 2300 I Street NW, Washington, DC 20037, USA

The George Washington Cancer Center, The George Washington University, Science & Engineering Hall, Ste 8300, Washington, DC 20052, USA

The Institute for Biomedical Sciences, The George Washington University, 2300 I Street NW, Ross Hall, Room 561, Washington, DC 20037, USA

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Alberto Bosque

*Author for correspondence: Tel.: +1 202 994 9696;

E-mail Address: abosque@gwu.edu

https://orcid.org/0000-0002-8800-2160

The Institute for Biomedical Sciences, The George Washington University, 2300 I Street NW, Ross Hall, Room 561, Washington, DC 20037, USA

Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, 2300 I Street NW, Washington, DC 20037, USA

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Rohan Fernandes

**Author for correspondence: Tel.: +1 202 994 0899;

E-mail Address: rfernandes@gwu.edu

https://orcid.org/0000-0001-9439-4626

Department of Medicine, The George Washington University, 2300 I Street NW, Washington, DC 20037, USA

The George Washington Cancer Center, The George Washington University, Science & Engineering Hall, Ste 8300, Washington, DC 20052, USA

The Institute for Biomedical Sciences, The George Washington University, 2300 I Street NW, Ross Hall, Room 561, Washington, DC 20037, USA

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Published Online:3 Feb 2023https://doi.org/10.2217/nnm-2022-0311

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Abstract

Aim: To investigate Prussian blue nanoparticles (PBNPs) coated with the synthetic analog of dsRNA polyinosinic-polycytidylic acid (polyIC) for their ability to function as HIV latency reversing agents. Methods: A layer-by-layer method was used to synthesize polyIC-coated PBNPs (polyIC-PBNPs). PolyIC-PBNPs were stable and monodisperse, maintained the native absorbance properties of both polyIC and PBNPs and were obtained with high nanoparticle collection yield and polyIC attachment efficiencies. Results: PolyIC-PBNPs were more effective in reactivating latent HIV than free polyIC in a cell model of HIV latency. Furthermore, polyIC-PBNPs were more effective in promoting immune activation than free polyIC in CD4 and CD8 T cells. Conclusion: PBNPs function as efficient carriers of nucleic acids to directly reverse HIV latency and enhance immune activation.

Plain language summary

HIV is a virus that attacks and weakens the immune system. If left untreated, HIV infection leads to AIDS. To combat this, administration of antiretroviral therapy allows HIV to be controlled, and an infected individual may live a normal life. However, there is no cure for HIV because the virus persists within hidden reservoirs of latently infected cells that remain undetected by the immune system. A cure strategy currently under investigation in the field utilizes a latency reversing agent (LRA) to reactivate latent HIV with the goal of promoting a response from the immune system. To achieve this goal, this study used a nanoparticle-based method to administer LRAs. More specifically, the authors synthesized Prussian blue nanoparticles (PBNPs) coated with the LRA polyinosinic-polycytidylic acid (polyIC), a synthetic analog of dsRNA. This study demonstrates that when administered in the form of nanoparticles, polyIC-coated PBNPs generate both enhanced reactivation of HIV and immune activation when compared with free polyIC. These results indicate a promising potential for using PBNPs to deliver LRAs such as polyIC to enhance current and future HIV cure strategies.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 17, No. 29

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History

Received 8 December 2022

Accepted 12 January 2022

Published online 3 February 2023

Published in print December 2022

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Keywords

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/nnm-2022-0311

Author contributions

PB Balakrishnan: conceptualization, data curation, formal analysis, investigation, methodology, visualization, writing – review and editing. CS Holmberg: conceptualization, data curation, formal analysis, investigation, methodology, visualization, writing – review and editing. DK Ledezma: investigation, methodology, writing – review and editing. A Bosque: conceptualization, funding acquisition, supervision, validation, writing – original draft, writing – review and editing. R Fernandes: conceptualization, funding acquisition, supervision, validation, writing – original draft, writing – review and editing.

Acknowledgments

The authors would also like to acknowledge imaging support provided by The George Washington University Nanofabrication and Imaging Center (C Brantner).

Financial & competing interests disclosure

Research reported in this publication was supported in part by the George Washington Cancer Center and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R33AI136102 to R Fernandes. This work was also partially supported by the NIH under grant R01-AI124722 to A Bosque. CS Holmberg was supported by an NIH NIAID-funded grant, number T32 AI158105. This research was facilitated by the services and resources provided by the District of Columbia Center for AIDS Research, an NIH-funded program (AI117970), which is supported by the following NIH cofounding and participating institutes and centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, NIDDK, NIMHD, NIDCR, NINR, FIC and OAR. The content is the sole responsibility of the authors and does not represent the official views of the NIH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The research described in this study utilizes human peripheral blood mononuclear cells isolated from blood obtained from deidentified HIV-negative volunteers 17 years and older from the Gulf Coast Regional Blood Center (TX, USA). The authors do not have access to any identifying patient information (e.g., name, Social Security number, medical record number, pathology accession number or any other code) that would permit samples used in this study to be linked to individually identifiable living individuals. Hence, the studies followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

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PolyIC-coated Prussian blue nanoparticles as a dual-mode HIV latency reversing agent

Abstract

Plain language summary

References