Engineered nanosponges mitigate peripheral stress-induced neuroinflammation and restore cognitive function
- 1Duke University
Abstract
Systemic inflammation is increasingly recognized as a key driver of neuroinflammation and cognitive dysfunction, particularly in the aging population. Yet, therapeutic interventions that broadly attenuate circulating inflammatory mediators without suppressing host immunity remain limited. Here, we report the development of taurine functionalized hyaluronic acid nanosponges (HA Tau) that blunt systemic inflammatory cascades to protect against downstream neurocognitive impairment. Using molecular docking calculations and experimental validations, we show that taurine functionalization enhances multivalent interactions with diverse cytokines, enabling broad-spectrum sequestration of inflammatory proteins from both murine and human plasma while preserving the intrinsic hypochlorous acid neutralizing ability of taurine. In aged mice undergoing orthopedic surgery, systemic administration of HA Tau nanosponges lowered the levels of circulating inflammatory mediators, preserved blood brain barrier integrity, and attenuated glial cell activation. These effects were accompanied by improved hippocampal neuronal activity and spatial working memory in mice. By dampening peripheral inflammatory surges, the nanosponges limit peripheral-to-central inflammatory signaling without directly targeting the central nervous system. Collectively, these findings demonstrate systemic inflammatory modulation could be an effective strategy for mitigating peripheral insult-induced neuroinflammation and cognitive decline, and position HA Tau nanosponges as a versatile biomaterial platform for treating inflammation-driven disorders.
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BibTeX
@misc{perikamana2026engineered,
title = {{Engineered nanosponges mitigate peripheral stress-induced neuroinflammation and restore cognitive function}},
author = {S. Madhurakkat Perikamana and B. Maity and R. Dargis and R. Kikani and H. A. Rather and P. Brown and G. Cho and H. Newman and L. Duncan and G. Arya and S. Varghese},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.16.752213},
url = {https://www.biorxiv.org/content/10.64898/2026.09.16.752213v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Engineered nanosponges mitigate peripheral stress-induced neuroinflammation and restore cognitive function
AU - S. Madhurakkat Perikamana
AU - B. Maity
AU - R. Dargis
AU - R. Kikani
AU - H. A. Rather
AU - P. Brown
AU - G. Cho
AU - H. Newman
AU - L. Duncan
AU - G. Arya
AU - S. Varghese
PY - 2026
DA - 2026/09/16
PB - bioRxiv
DO - 10.64898/2026.09.16.752213
UR - https://www.biorxiv.org/content/10.64898/2026.09.16.752213v1
AB - Systemic inflammation is increasingly recognized as a key driver of neuroinflammation and cognitive dysfunction, particularly in the aging population. Yet, therapeutic interventions that broadly attenuate circulating inflammatory mediators without suppressing host immunity remain limited. Here, we report the development of taurine functionalized hyaluronic acid nanosponges (HA Tau) that blunt systemic inflammatory cascades to protect against downstream neurocognitive impairment. Using molecular docking calculations and experimental validations, we show that taurine functionalization enhances multivalent interactions with diverse cytokines, enabling broad-spectrum sequestration of inflammatory proteins from both murine and human plasma while preserving the intrinsic hypochlorous acid neutralizing ability of taurine. In aged mice undergoing orthopedic surgery, systemic administration of HA Tau nanosponges lowered the levels of circulating inflammatory mediators, preserved blood brain barrier integrity, and attenuated glial cell activation. These effects were accompanied by improved hippocampal neuronal activity and spatial working memory in mice. By dampening peripheral inflammatory surges, the nanosponges limit peripheral-to-central inflammatory signaling without directly targeting the central nervous system. Collectively, these findings demonstrate systemic inflammatory modulation could be an effective strategy for mitigating peripheral insult-induced neuroinflammation and cognitive decline, and position HA Tau nanosponges as a versatile biomaterial platform for treating inflammation-driven disorders.
ER -