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Magnetically navigated nano-PROTAC ameliorates acute lung injury
Sheng Chen1,2, Enen Chen1, Jianfen Su1
1The Affiliated Panyu Central Hospital, The Fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, P. R. China.
This study introduces nano-PROTAC (EMPLANT), a novel therapy for acute lung injury (ALI). EMPLANT uses magnetic navigation to target inflamed lungs, reprogramming macrophages and significantly improving survival rates in ALI models.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Immunology
Background:
- Acute lung injury (ALI) is a severe inflammatory condition with high mortality.
- Current treatments for ALI lack efficacy, leading to poor patient outcomes.
Purpose of the Study:
- To develop and evaluate a novel nano-PROTAC system for targeted ALI therapy.
- To investigate the mechanism of macrophage reprogramming in ALI treatment.
Main Methods:
- Engineered nano-PROTAC (EMPLANT) using PLGA, magnetic nanoparticles, and TRIM24-targeted PROTAC, camouflaged with M1 macrophage-derived exosomes.
- Evaluated EMPLANT's physicochemical properties, cellular uptake, toxicity, anti-inflammatory effects, biodistribution, and therapeutic efficacy in ALI mouse models.
Main Results:
- EMPLANT demonstrated dual-targeting via magnetic navigation and inflammatory specificity.
- EMPLANT selectively accumulated in inflamed lungs, reduced injury, and prolonged survival in ALI mice.
- TRIM24 degradation upregulated STAT6, promoting M1 to M2 macrophage phenotypic switch, ameliorating ALI and increasing survival to nearly 100%.
Conclusions:
- Nano-PROTAC (EMPLANT) offers a promising therapeutic strategy for ALI by reprogramming macrophages in situ.
- This represents the first development of magnetically navigated artificial exosomes for PROTAC delivery in ALI treatment.
