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Development of TIMP1 magnetic nanoformulation for regulation of synaptic plasticity in HIV-1 infection

Authors Atluri V, Jayant RD, Pilakka-Kanthikeel S, Garcia G, Samikkannu T, Yndart A, Kaushik A, Nair M

Received 12 March 2016

Accepted for publication 15 May 2016

Published 31 August 2016 Volume 2016:11 Pages 4287—4298

DOI https://doi.org/10.2147/IJN.S108329

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 3

Editor who approved publication: Professor Carlos Rinaldi


Venkata Subba Rao Atluri* Rahul Dev Jayant* Sudheesh Pilakka-Kanthikeel, Gabriella Garcia, Thangavel Samikkannu, Adriana Yndart, Ajeet Kaushik, Madhavan Nair

Center for Personalized Nanomedicine, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA

*These authors contributed equally to this work

Abstract: Although the introduction of antiretroviral therapy has reduced the prevalence of severe forms of neurocognitive disorders, human immunodeficiency virus (HIV)-1-associated neurocognitive disorders were observed in 50% of HIV-infected patients globally. The blood–brain barrier is known to be impermeable to most of antiretroviral drugs. Successful delivery of antiretroviral drugs into the brain may induce an inflammatory response, which may further induce neurotoxicity. Therefore, alternate options to antiretroviral drugs for decreasing the HIV infection and neurotoxicity may help in reducing neurocognitive impairments observed in HIV-infected patients. In this study, we explored the role of magnetic nanoparticle (MNP)-bound tissue inhibitor of metalloproteinase-1 (TIMP1) protein in reducing HIV infection levels, oxidative stress, and recovering spine density in HIV-infected SK-N-MC neuroblastoma cells. We did not observe any neuronal cytotoxicity with either the free TIMP1 or MNP-bound TIMP1 used in our study. We observed significantly reduced HIV infection in both solution phase and in MNP-bound TIMP1-exposed neuronal cells. Furthermore, we also observed significantly reduced reactive oxygen species production in both the test groups compared to the neuronal cells infected with HIV alone. To observe the effect of both soluble-phase TIMP1 and MNP-bound TIMP1 on spine density in HIV-infected neuronal cells, confocal microscopy was used. We observed significant recovery of spine density in both the test groups when compared to the cells infected with HIV alone, indicting the neuroprotective effect of TIMP1. Therefore, our results suggest that the MNP-bound TIMP1 delivery method across the blood–brain barrier can be used for reducing HIV infectivity in brain tissue and neuronal toxicity in HIV-infected patients.

Keywords: HIV, neurocognitive disorders, TIMP1, magnetic nanoparticles, blood–brain barrier, neuroprotection

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