# An innovative hemoperfusion nanotrap for sepsis treatment.

> **NIH NIH R01** · UPSTATE MEDICAL UNIVERSITY · 2020 · $380,151

## Abstract

Abstract
 Sepsis causes >250,000 deaths each year in the USA. Lipopolysaccharide (LPS), shed by gram-negative
bacteria, alone is sufficient to induce cytokine storm and sepsis. Meanwhile, many other infections and
diseases can also cause sepsis. Sepsis is complex, dynamic, and heterogeneous in both etiology and
progression, which has led to failures of almost all unimodal immune modulation therapies. The systemic
hyperinflammation in sepsis is generally induced by circulating LPS, pathogenic and damage molecules and
signaling molecules (e.g. cytokines). Therefore, physical clearance of these septic triggers and mediators from
blood is a valid approach for sepsis treatment. A polymyxin B-coated cartridge, Toraymyxin®, has been used to
remove LPS specifically by hemoperfusion (HP). Recently, a Cytosorb® cartridge packed with macroporous
resin is used to remove cytokines through nonspecific hydrophobic adsorption. Unfortunately, both products
failed in the most recent double-blind controlled clinical trials for sepsis treatment, which is likely due to the
moderate efficiency and limited adsorption profiles of both cartridges. In addition, various proinflammatory
damage molecules should also be removed for the treatment to be effective. Therefore, we hypothesize that
the efficient and simultaneous removal of both septic triggers and mediators from the circulation will
control hyperinflammation in sepsis, and thus reducing both morbidity and mortality associated with
severe sepsis and septic shock. The PI has developed a versatile telodendrimer (TD) nanoplatform for
efficient binding to LPS, cytokines, and DNA fragments via the combination of multivalent and synergistic
charge and hydrophobic interactions. Such TD nanotraps can be conjugated onto size-exclusive hydrogel
resins to target these small-sized proinflammatory molecules. These nanotrap resins are able to selectively
scavenge LPS and proinflammatory cytokines efficiently in the blood from septic mice with much higher
efficiencies than existing commercial resins. The charge and hydrophobic moieties in the nanotrap can be
easily engineered to target a specific group of inflammatory molecules to optimize sepsis treatment. Aim 1, we
will focus on synthesis and optimization of TD nanotraps with different charges and hydrophobic moieties on
hydrogel resins and characterize the selectivity and efficiency in adsorbing LPS, DAMP/PAMPs and cytokines;
Aim 2, We will conduct comprehensive in vitro studies to characterize the refined nanotrap adsorption and
understand the molecular basis in attenuating hyper-immune reactions; Aim 3, we will study the efficacy of
nanotrap HP approach in Cecal Ligation and Puncture (CLP) septic rat model and characterize the in vivo
immune reactions and pathological improvement in preventing multiple organ failure. These studies will pave
the way to translate this innovative HP nanotrap technique into the clinic to improve the survival of patients with
severe sepsis and sep...

## Key facts

- **NIH application ID:** 9974537
- **Project number:** 5R01GM130941-03
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** Juntao Luo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,151
- **Award type:** 5
- **Project period:** 2018-09-20 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974537

## Citation

> US National Institutes of Health, RePORTER application 9974537, An innovative hemoperfusion nanotrap for sepsis treatment. (5R01GM130941-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9974537. Licensed CC0.

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