DLin-MC3-DMA
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Ionizable lipid for LNP and nucleic-acid delivery research.
AA-T3A-C12 is a leading anisamide-tethered lipidoid (AA-lipidoid) identified through a combinatorial library screening for targeted RNA delivery to activated fibroblasts, offering a promising approach to treat liver fibrosis.AA-T3A-C12 is a leading anisamide-tethered lipidoid (AA-lipidoid) identified through a combinatorial library screening for targeted RNA delivery to activated fibroblasts, offering a promising approach to treat liver fibrosis. It is synthesized via a one-pot, two-step modular method that combines anisamide—a ligand for sigma receptors overexpressed on activated hepatic stellate cells (HSCs)—with a T3A polyamine core and C12 epoxide tails, enabling efficient siRNA encapsulation in lipid nanoparticles (LNPs). In vitro, AA-T3A-C12 LNPs exhibit enhanced cellular uptake and gene silencing in activated fibroblasts, dependent on sigma receptor binding, as confirmed by haloperidol blockade studies, and outperform non-targeted analogs and the FDA-approved MC3 LNPs in fibroblast selectivity.In a mouse model of CCl4-induced liver fibrosis, AA-T3A-C12/siHSP47 LNP achieves approximately 65% knockdown of heat shock protein 47 (HSP47), a key fibrotic target, leading to significant reduction in collagen deposition and fibrosis alleviation, with a good safety profile and no exacerbation of liver injury.
| CAS No. | Not available |
| Chemical Name | AA-T3A-C12 |
| Synonyms | AAT3AC12, AA T3A C12 |
| SMILES | OC(CCCCCCCCCC)CN(CC(O)CCCCCCCCCC)CCCN(CCCNC(C1=CC=C(OC)C=C1)=O)CCCN(CC(O)CCCCCCCCCC)CC(O)CCCCCCCCCC |
| Formula | C65H126N4O6 |
| M.Wt | 1,059.72 |
| Purity | ELSD-HPLC>95% |
| Storage | Pure form: −20 °C, 1 year; In solvent: −80 °C, 6 months; −20 °C, 1 month. Sealed and protected from light. |
| Shipping condition | Ships from Shanghai. Pure lipid is stable during ice-pack transport. |
| Publication | Han X, Gong N, Xue L, et al. Ligand-tethered lipid nanoparticles for targeted RNA delivery to treat liver fibrosis. Nature Communications. 2023;14:75. |
| Component | mol% | Role |
|---|---|---|
| AA-T3A-C12 | 50 | Ionizable lipid |
| DSPC | 10 | Helper phospholipid |
| Cholesterol | 38.5 | Sterol |
| C14-PEG2000 | 1.5 | PEG lipid |
| Reported total | 100 | Source values retained |
| Parameter | Reported result | Source |
|---|---|---|
| Size (DLS) | 65.6 ± 1.2 nm | Supplementary Table S1 |
| PDI | 0.018 | Supplementary Table S1 |
| Encapsulation efficiency | 87.4 ± 3.8% | Supplementary Table S1 |
| Zeta potential | −1.1 ± 1.5 mV | Supplementary Table S1 |
| Apparent pKa (TNS) | 5.72 | Main article, characterization |
Main PDF p.2, Fig. 1a; p.4, Characterization; pp.9-10, LNP formulation and characterization; SI p.27, Table S1
Predominant liver localization, with no significant difference in total liver accumulation versus MC3 (p=0.443). Confocal microscopy showed more AA-T3A-C12 signal colocalized with or near alpha-SMA-positive activated HSCs than MC3.
5 micrograms/mouse IV; fibrotic male BALB/c mice; organs at 1 h; n=3 · Main PDF p.6, Fig. 5a and p.8 caption; SI p.20, Fig. S20; Source Data 'Fig 5a'!B7:K12In fibrotic mice, AA-T3A-C12/siGFP LNP did not significantly increase ALT, AST or TBIL versus the PBS disease control; cytokines were not increased by LNP regimens and no histological damage was observed in heart, spleen, lung or kidney.
This is tolerability in a CCl4 injury model under one repeated-dose regimen, not a general toxicology package. · Main PDF pp.6-8, Fig. 6c-e; SI pp.23-24, Figs. S22-S23; Source Data 'Fig 6c'!B4:F9, 'Fig 6d'!B6:F11, 'Fig 6e'!B6:F11, 'Fig S22'!B3:M9The product molecular weight is prefilled when available and remains editable. Confirm solvent compatibility and solubility before preparation.
Solvent volumes update from the molecular weight above.
| Mass | 1 mM | 5 mM | 10 mM |
|---|---|---|---|
| 10 mg | 9.4365 mL | 1.8873 mL | 943.65 μL |
| 25 mg | 23.5911 mL | 4.7182 mL | 2.3591 mL |
| 50 mg | 47.1823 mL | 9.4365 mL | 4.7182 mL |
| 100 mg | 94.3645 mL | 18.8729 mL | 9.4365 mL |
| 250 mg | 235.9114 mL | 47.1823 mL | 23.5911 mL |
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