NIH grant: DHA-loaded nanoparticles for inflammation resolution therapy (1R01HL185536-01)

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NIH grant 1R01HL185536-01: DHA-loaded nanoparticles for inflammation resolution therapy
Institute: {'code': 'HL', 'abbreviation': 'NHLBI', 'name': 'National Heart Lung and Blood Institute', 'admin_org_id': '12500068', 'admin_funding_url': ''}. PI: Zhenjia  Wang. Award: $502773.
Start: 2026-08-01T00:00:00.
DHA-loaded Nanoparticles for Inflammation Resolution Therapy
 Inflammation is an immune response to protect against tissue injury or infections, but if unresolved,
inflammation causes a wide range of diseases, such as acute lung inflammation/injury (ALI), stroke, myocardial
infarction, atherosclerosis, diabetes, and rheumatoid arthritis. Acute lung inflammation/injury (ALI) is a
dysregulated inflammation disease, and it quickly precipitates to a severe form, acute respiratory distress
syndrome (ARDS). The mortality of ARDS is unacceptably high at 30-50%, but there are no pharmacological
therapies except lung-protection ventilation and fluid-conservative management. Most therapies have been
developed to blunt the immune response using anti-inflammatory agents. However, clinical trials have shown
that those treatments do not have clear benefits and have significant undesired side effects, such as increased
host susceptibility to secondary infections.
 Inflammation resolution is a new and novel therapy mediated by endogenous specialized pro-solving lipid
mediators (SPMs) and they are mainly produced from ω-3 polyunsaturated fatty acids (PUFAs).
Docosahexaenoic acid (DHA) is a major component of PUFAs and biosynthesizes resolvins, one type of SPMs.
The well-studied resolvins RvD1 and RvD2 show the potent multifaceted actions for inflammation resolution to
mitigate inflammatory diseases. But their clinical translation is challenging because chemical synthesis of
resolvins is difficult, and immune cells (neutrophils) are required to provide lipoxygenase (LOX) to metabolize
DHA to produce resolvins. Activated (inflammatory) neutrophils are a major source of LOX. Neutrophils play a
central role in pathogenesis of ALI/ARDS, and they are sequestered in the lungs during ALI. Therefore, ALI is
an excellent disease model to evaluate our hypothesis on inflammation resolution therapies. My lab has expertise
in ALI/ARDS models and nanoparticle neutrophil targeting; thus, the proposal is feasible and would impact on
ALI therapies. There are three specific aims: Aim 1: Investigate ionizable cationic lipid-based DHA-liposomes for
improved neutrophil delivery and DHA release. Aim 2: Optimize biosynthesis of resolvins from DHA-liposomes
in vivo. Aim 3: Determine therapeutic effects of DHA-liposomes in vivo. The success of this proposal would
impact on the development of host-directed therapies to treat a wide range of inflammatory disorders and
autoimmune diseases.

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