# GM3 Nanoparticles for Sustained Delivery of Anti-Retrovirals to Lymphatic Tissues

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $637,477

## Abstract

PROJECT ABSTRACT
Despite widespread implementation of antiretroviral therapy (ART) that effectively suppresses virus replication
in the periphery, HIV persists in tissue reservoirs and accounts for the rapid plasma viral rebound in HIV-
infected individuals who have discontinued ART. It is well appreciated that secondary lymphoid tissues
represent a drug-privileged site that account for residual viral persistence in HIV-infected individuals on ART.
Hence, effective cure and eradication strategies require development of novel approaches that specifically
target lymph node-resident HIV reservoirs. An effective strategy to enhance anti-retroviral (ARV) drug
concentrations in secondary lymph nodes is to formulate ARVs in carriers such as nanoparticles that promote
transport of compounds via the lymphatics to the draining lymph nodes. Additionally, strategies that prevent
rapid clearance and maintain inhibitory concentrations of ARVs in lymph nodes for an extended time are
needed to effectively suppress persistent virus expression. Hence in this application, we are proposing to
develop GM3-containing membrane encapsulated nanoparticle-based approaches to establish long-term
tissue depots of ARVs in lymph nodes to suppress residual viral replication. The design of these nanoparticles
is based on our recent findings that demonstrate specific capture of GM3 (α2,3-linked sialic acid containing
monosialo-dihexosylganglioside) containing membrane encapsulated gold nanoparticles by CD169 expressing
primary human myeloid cells such as macrophages and dendritic cells in vitro and co-localization of GM3-gold
NPs with CD169+ cells in lymph nodes of mice. Interestingly, capture of GM3-gold NPs resulted in
sequestration and preservation within surface accessible non-lysosomal plasma membrane invaginations in
CD169+ myeloid cells. Hence, we will exploit these specific interactions between GM3-containing membrane
encapsulated nanoparticles and CD169 to achieve both selective targeting of lymph node resident-myeloid
cells and sequestration to specialized non-lysosomal compartments for formation of “drug depots” that achieve
sustained inhibitory concentrations of ARVs. Finally, we will determine the ability of these novel ARV-
containing nanocarriers to suppress virus replication in lymph nodes in a humanized mouse model of HIV-1
infection. We believe these studies are critical to development of virus-eradication strategies for eliminating
persistent HIV reservoir.

## Key facts

- **NIH application ID:** 9815955
- **Project number:** 5R01AI132111-03
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** SURYARAM GUMMULURU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $637,477
- **Award type:** 5
- **Project period:** 2017-11-08 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9815955

## Citation

> US National Institutes of Health, RePORTER application 9815955, GM3 Nanoparticles for Sustained Delivery of Anti-Retrovirals to Lymphatic Tissues (5R01AI132111-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9815955. Licensed CC0.

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