Биологическая активность
The AA15 липид, an amino acid-derived ионизируемый липид, integrates a carboxylic acid-containing headgroup and biodegradable branched ester tails (R2) to enhance mRNA delivery. Optimized as AA15V LNP, it exhibits a hydrodynamic diameter of 102.3 ± 4.1 nm, low polydispersity (PDI <0.15), and slightly positive zeta potential (+4–6 mV), enabling efficient tumor-targeted delivery. With a pKa ~6.1–6.4, AA15V ensures protonation in acidic endosomes, promoting mRNA release. It achieves >85% mRNA encapsulation efficiency, critical for stable saRNA delivery. in vitro, AA15V LNP-sSE-SCTs induced sustained SE-SCT expression (69% H-2Kb+β2m+ B16F10 cells at 72 h), outperforming mRNA formulations. in vivo, a single intratumoral dose of AA15V LNP-sSE-SCTs suppressed tumor growth by 22-fold in vaccinated mice, synergizing with checkpoint inhibitors (anti-PD-1/CTLA-4) for complete regression in 28.6% of lymphoma models. Ex vivo, AA15V enabled SE-SCT expression in human glioblastoma (7.1% CD45− cells) and lung cancer samples (5.8–8.7%), underscoring clinical potential. Key data: pKa ~6.3; encapsulation: 85–89%; zeta: +4–6 mV; size: 102.3 ± 4.1 nm.
Оригинал на английском
The AA15 lipid, an amino acid-derived ionizable lipid, integrates a carboxylic acid-containing headgroup and biodegradable branched ester tails (R2) to enhance mRNA delivery. Optimized as AA15V LNP, it exhibits a hydrodynamic diameter of 102.3 ± 4.1 nm, low polydispersity (PDI <0.15), and slightly positive zeta potential (+4–6 mV), enabling efficient tumor-targeted delivery. With a pKa ~6.1–6.4, AA15V ensures protonation in acidic endosomes, promoting mRNA release. It achieves >85% mRNA encapsulation efficiency, critical for stable saRNA delivery. In vitro, AA15V LNP-sSE-SCTs induced sustained SE-SCT expression (69% H-2Kb+β2m+ B16F10 cells at 72 h), outperforming mRNA formulations. In vivo, a single intratumoral dose of AA15V LNP-sSE-SCTs suppressed tumor growth by 22-fold in vaccinated mice, synergizing with checkpoint inhibitors (anti-PD-1/CTLA-4) for complete regression in 28.6% of lymphoma models. Ex vivo, AA15V enabled SE-SCT expression in human glioblastoma (7.1% CD45− cells) and lung cancer samples (5.8–8.7%), underscoring clinical potential. Key data: pKa ~6.3; encapsulation: 85–89%; zeta: +4–6 mV; size: 102.3 ± 4.1 nm.
Химические свойства
- Брутто-формула
- C₅₉H₁₁₆O₇N₂
- Мол. масса
- 965.58 г/моль
- SMILES
- CCCCCC(CC)OC(=O)CCCCCCCCN(CCCCCO)CCCN(CCCCCCCCC(=O)OC(CC)CCCCC)CCCCCCCCC(=O)OC(CC)CCCCC
- Синонимы
- LipidAA15， Lipid-AA15
3D-структура молекулы
Вращайте мышью · Колесо — масштаб
Хранение и физические свойства
- Условия хранения
- 2 года -20°C порошок, 2 недели 4°C в ДМСО, 6 мес. -80°C в ДМСО Publication: LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment Y Xue, X Hou, Y Zhong, Y Zhang, S Du, DD Kang… - Nature Communications, 2025
Безопасность и документация
Только для научно-исследовательского применения. Не предназначено для использования у пациентов или в качестве лекарственного средства.