Биологическая активность
HCQ-4 is a rationally engineered ионизируемый липид derived from hydroxychloroquine (HCQ), featuring a ditetradecylamine-derived twin-C14 saturated hydrocarbon tail linked to the HCQ headgroup via a succinic acid spacer. Synthesized through a three-step route involving HCQ deprotonation, ditetradecylamine carboxylation, and EDC/DMAP-mediated amidation, this липид forms the core of optimized липид nanoparticles (LNPs) at a molar ratio of 60:10:40:0.5 (HCQ-4:DOPE:cholesterol:DMG PEG 2000 ). The structure enables dual functionality: (1) Spleen-селективный mRNA delivery (2.3-fold higher splenic vs. hepatic transfection) via 80-100 nm particle size, near-neutral charge (-3 mV), and low PEG density, facilitating immune клетка uptake; (2) Tumor microenvironment modulation through HCQ-mediated repolarization of M2 macrophages to antitumor M1 phenotype (iNOS + cells ↑2.5-fold, CD206 + cells ↓60%). This bifunctional design synergistically enhances mRNA cancer vaccine efficacy, demonstrating superior prophylactic/therapeutic antitumor activity and antimetastatic effects compared to clinical benchmarks like MC-3 LNP.
Оригинал на английском
HCQ-4 is a rationally engineered ionizable lipid derived from hydroxychloroquine (HCQ), featuring a ditetradecylamine-derived twin-C14 saturated hydrocarbon tail linked to the HCQ headgroup via a succinic acid spacer. Synthesized through a three-step route involving HCQ deprotonation, ditetradecylamine carboxylation, and EDC/DMAP-mediated amidation, this lipid forms the core of optimized lipid nanoparticles (LNPs) at a molar ratio of 60:10:40:0.5 (HCQ-4:DOPE:cholesterol:DMG PEG 2000 ). The structure enables dual functionality: (1) Spleen-selective mRNA delivery (2.3-fold higher splenic vs. hepatic transfection) via 80-100 nm particle size, near-neutral charge (-3 mV), and low PEG density, facilitating immune cell uptake; (2) Tumor microenvironment modulation through HCQ-mediated repolarization of M2 macrophages to antitumor M1 phenotype (iNOS + cells ↑2.5-fold, CD206 + cells ↓60%). This bifunctional design synergistically enhances mRNA cancer vaccine efficacy, demonstrating superior prophylactic/therapeutic antitumor activity and antimetastatic effects compared to clinical benchmarks like MC-3 LNP.
Химические свойства
- Брутто-формула
- C₅₀H₈₇O₃ClN₄
- Мол. масса
- 827.72 г/моль
- SMILES
- CCCCCCCCCCCCCCN(CCCCCCCCCCCCCC)C(=O)CCC(=O)OCCN(CC)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1
- Синонимы
- HCQ-Lipid-4，Lipid 4
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
Безопасность и документация
Только для научно-исследовательского применения. Не предназначено для использования у пациентов или в качестве лекарственного средства.