Lipid 2231
Recommended because it shares a closely related research category or delivery context. Formulation and performance are product- and study-specific.
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Components are supplied separately; this is not a premixed LNP. RNA/cargo, buffer and formulation service are not included.
PL-40 is a cardiolipin-mimetic ionizable lipid engineered for high-efficiency, antibody-free mRNA delivery to T cells. PL 40 LNPs exhibit a mean particle size of 120 nm, zeta potential of -5.19 mV, and >80% mRNA encapsulation efficiency, with excellent plasma stability (≤5% size change after 6h in serum). Cryo-TEM reveals polyhedral nanoparticles with phase-separated domains, while SAXS confirms tight mRNA packing (d-spacing: ~3 nm vs. 6.64 nm in conventional LNPs). AFM demonstrates exceptional rigidity (high bending modulus), enabling T cell-selective uptake via actin-mediated endocytosis (>2× higher than ALC0315 LNPs).In primary human T cells, PL40 LNPs achieve >90% transfection at 0.5 μg mRNA dose and sustain >100× higher luciferase expression than benchmark lipids. When delivering circular RNA, they extend protein expression >5 days with superior spleen tropism (spleen:liver ratio = 2.63). Crucially, they reprogram T cells into functional CAR-Ts in vivo without antibody conjugation, evading exhaustion markers (no Tim-3/PD-1 upregulation). Therapeutically, PL40-based uPAR-targeted CAR mRNA reduces liver fibrosis (collagen↓50%, ALT↓50%) and rheumatoid arthritis severity (clinical scores↓60%) by clearing senescent cells. Humanized anti-uPAR CARs delivered via PL40 show near-complete cytotoxicity (>95%) against uPAR+ cells, underscoring clinical translatability.
| CAS No. | Not available |
| Chemical Name | Lipid PL40 |
| Synonyms | Lipid-PL40, PL 40, PL-40, CAMP lipid PL40 |
| SMILES | CCCCCCCCC(CC)OC(=O)CCCCCCCOP(=O)(NCCCN1CCN(CCCNP(=O)(OCCCCCCCC(=O)OC(CC)CCCCCCCC)OCCCCCCCC(=O)OC(CC)CCCCCCCC)CC1)OCCCCCCCC(=O)OC(CC)CCCCCCCC |
| Formula | C86H170N4O14P2 |
| M.Wt | 1,546.27 |
| 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 | Zhang Z, Ma B, Li B, et al. Cardiolipin-mimic lipid nanoparticles without antibody modification delivered senolytic in vivo CAR-T therapy for inflamm-aging. Cell Reports Medicine. 2025;6:102209. |
| Component | mol% | Role |
|---|---|---|
| PL40 | Not reported | Ionizable lipid |
| DOPE | Not reported | Helper phospholipid |
| Cholesterol | Not reported | Sterol |
| DMG-PEG2000 | Not reported | PEG lipid |
| Reported total | Not reported | Source values retained |
More than 80% of primary human T cells were GFP-positive at tested doses of at least 0.5 micrograms mRNA per 100,000 cells.
GFP mRNA; 40 h; n=3 · Main Figure 2C and Supplementary Figure S1DDisplayed GFP-positive fractions for circular versus linear mouse-uPAR CAR mRNA were 99.7% versus 86.5% on day 1, 97.4% versus 7.5% on day 2, 94.3% versus 5.0% on day 3 and 17.1% versus 4.6% on day 5.
PL40; 0.5 micrograms mRNA per 100,000 mouse T cells · Main Figure 4D, article pp. 8-9 / PDF pp. 9-10Circular mouse-uPAR CAR mRNA/PL40 reduced serum ALT, senescence-associated beta-galactosidase staining, collagen coverage and hepatic uPAR relative to PBS in the reported CCl4 model.
30 micrograms mRNA per mouse, IV every four days for four doses; endpoint day 15 · Main Figure 5 and Supplementary Figure S13Six IV doses reduced the final clinical score and paw thickness and improved histologic endpoints relative to untreated or vehicle groups in the reported mouse model.
30 micrograms mRNA per mouse, IV every four days for six doses from day 28 · Main Figure 6 and Supplementary Figure S18After a single 1.5 mg/kg IV dose, the study reported no major liver or spleen histologic injury and no significant ALT, AST, BUN or creatinine flags through day 11; some hematology indices fluctuated during the first three days but were described as within normal ranges.
C57BL/6 mice; n=3 per time point; short-term single-dose study · Main text p. 14 and Supplementary Figure S21The 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 | 6.4672 mL | 1.2934 mL | 646.72 μL |
| 25 mg | 16.1679 mL | 3.2336 mL | 1.6168 mL |
| 50 mg | 32.3359 mL | 6.4672 mL | 3.2336 mL |
| 100 mg | 64.6718 mL | 12.9344 mL | 6.4672 mL |
| 250 mg | 161.6794 mL | 32.3359 mL | 16.1679 mL |
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