tLyP-1 peptide-modified MnO₂ co-delivering si-SLC16A1 and temozolomide synergistically suppresses glioblastoma via hypoxia modulation and metabolic stress - PubMed
7 hours ago
- #glioblastoma
- #hypoxia-modulation
- #nanoparticles
- Development of tLyP-1-modified MnO₂ nanoparticles (tLyP-NPs) for co-delivery of temozolomide (TMZ) and SLC16A1 siRNA to treat glioblastoma (GBM).
- tLyP-NPs generate oxygen via H₂O₂ decomposition, alleviating tumor hypoxia and enhancing MRI imaging through Mn²⁺ release.
- In vitro studies showed high siRNA loading, pH-responsive drug release, effective SLC16A1 silencing, and reduced glioma cell viability.
- tLyP-1 modification improved blood-brain barrier (BBB) penetration and glioma targeting, increasing cellular uptake in co-culture models.
- In orthotopic GBM rat models, tLyP-NPs demonstrated superior tumor accumulation, prolonged MRI contrast, and enhanced therapeutic efficacy.
- SLC16A1 silencing led to lactate accumulation, suppressed HCAR1/PI3K/AKT signaling, and promoted apoptosis in vitro and in vivo.
- Histological analysis confirmed tumor necrosis, increased apoptosis, reduced proliferation, and alleviated hypoxia.
- Survival analysis showed prolonged survival without systemic toxicity, highlighting tLyP-NPs as a promising multifunctional nanoplatform.