Neutrophil-mediated delivery of curcumin-loaded manganese-doped zeolitic imidazolate framework-8 nanozymes for pulmonary arterial hypertension - PubMed
6 hours ago
- #pulmonary-hypertension
- #drug-delivery
- #nanomedicine
- Pulmonary arterial hypertension (PAH) is a severe vascular disease with oxidative stress, inflammation, and vascular remodeling.
- Current PAH therapies only offer symptomatic relief without reversing disease progression.
- A targeted nanotherapeutic platform (NEMZC) was developed using neutrophil-mediated delivery of curcumin-loaded Mn-doped ZIF-8 nanozymes.
- NEMZC showed high drug loading (~80% encapsulation efficiency) and pH-responsive release (82% curcumin release at pH < 6.0 in 12 h).
- In vitro, NEMZC reduced α-SMA expression by 75% and increased CD31 expression by 3.3-fold, indicating strong anti-EndoMT effects.
- NEMZC shifted macrophage polarization, decreasing M1 markers (iNOS by 75%) and increasing M2 markers (CD206 by ~3.2-fold).
- In PAH mice, NEMZC reduced pulmonary arterial pressure from 57.2 mmHg to 20.7 mmHg and decreased collagen deposition by ~70%.
- NEMZC modulated the PI3K-NF-κB pathway, demonstrating dual antioxidant/anti-inflammatory action and EndoMT inhibition.
- The study suggests NEMZC as a safe, targeted, and multifunctional cell-based nanoplatform with strong clinical translation potential.