C18 NC-TNP
DC60537
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Literature evidence · DC67520
Formulation & Performance
Detailed composition, particle sizes, cell expression and mouse biodistribution from Cheng et al. (2025) and its SI.
The source identifies nor-MC3 in SI Figure S1. The 2026 RSC paper is a separate related reference; results for nor-KC2 are not assigned to nor-MC3.
Formulation components and molecular-weight conversion
| Component | DC Chemicals product | Molecular weight | Molar ratio | Mass at 1 µmol total lipid (mg) |
|---|---|---|---|---|
| nor-MC3 | DC67520 | 614.06 | 20 | 0.120997 |
| Egg sphingomyelin (ESM) | Not uniquely mapped | Not established | 40 | Not calculable from disclosed data |
| Cholesterol | DCD-041 | 386.65 | 40 | 0.152374 |
| DMG-PEG2000 / PEG-DMG | DC40169 | 2507 | 1.5 | 0.037049 |
The selected study condition is R(B/I)=4. Ratios 20:40:40:1.5 are relative molar parts and sum to 101.5, not 100%. The calculator normalizes parts. ESM is a mixture with no single assigned MW here. DMG-PEG2000 uses the DC Chemicals catalog convention of 2507. Study NanoLuc N/P=6; not a mass ratio.
Component mass calculator
Not all inputs are assigned to a single verified study formulation; unassigned fields are blank. Enter your own values to calculate a research scenario. Molecular weights and ratios are editable. Results are calculated, not measured study data. No N/P or RNA dose is inferred.
| Component | MW | Molar ratio | Mass (mg) | Mass % |
|---|---|---|---|---|
| nor-MC3 | ||||
| Egg sphingomyelin (ESM) | ||||
| Cholesterol | ||||
| DMG-PEG2000 / PEG-DMG |
Composition series and particle size
| R(B/I) | nor-MC3:ESM:Chol:PEG-DMG | Number mean nm | Z-average nm | PDI |
|---|---|---|---|---|
| 9 | 10:45:45:1.5 | 53.0 ± 1.3 | 77.4 ± 0.8 | 0.10 ± 0.01 |
| 4 | 20:40:40:1.5 | 45.4 ± 2.2 | 64.4 ± 0.2 | 0.09 ± 0.01 |
| 2.3 | 30:35:35:1.5 | 41.4 ± 1.9 | 61.7 ± 0.4 | 0.12 ± 0.01 |
| 1.5 | 40:30:30:1.5 | 40.2 ± 0.6 | 60.8 ± 0.6 | 0.14 ± 0.02 |
| 1 | 50:25:25:1.5 | 42.8 ± 0.7 | 63.5 ± 0.4 | 0.12 ± 0.01 |
| 0.67 | 60:20:20:1.5 | 49.2 ± 0.6 | 63.4 ± 0.2 | 0.05 ± 0.01 |
| 0.43 | 70:15:15:1.5 | 66.4 ± 1.6 | 90.4 ± 0.7 | 0.09 ± 0.01 |
SI Table S1 and accompanying DLS panels, p. 2; mean ± SD, n=3. NanoLuc mRNA; N/P=6 throughout. Number mean and Z-average are not interchangeable.
Cell-based evidence and formulation comparator
| Condition | Finding | Source |
|---|---|---|
| Huh7 cells; NanoLuc mRNA | Expression compared across the R(B/I) series; liposomal compositions retained transfection competency. | 24 h, 0.1-1 microgram mRNA/mL; main Fig. 1F, n=6, mean ± SEM. |
| Comparator | MC3:DSPC:cholesterol:PEG-DMG, 50:10:38.5:1.5. | SI Table S1: number mean 36.7 ± 0.5 nm; Z-average 53.9 ± 0.2 nm; PDI 0.13 ± 0.01. |
| Interpretation | The comparison changes lipid identity and helper-lipid composition together. | It does not isolate an intrinsic potency advantage of nor-MC3 over MC3. |
Mouse reporter expression and particle biodistribution
| Endpoint | Reported result | Context |
|---|---|---|
| Reporter expression | Approximately 50-fold greater spleen and 150-fold greater inguinal lymph-node luminescence than the comparator. | Female CD-1 mice; 0.5 mg/kg NanoLuc mRNA IV; tissue analysis 24 h; main Fig. 2C / SI Fig. S4. |
| Circulation | Approximately 15-fold longer circulation half-life. | Radiolabelled LNP study; main Fig. 2D-E / SI Figs. S7-S9. Radiotracer accumulation is distinct from functional expression. |
| Tissue-level expression | mCherry signal colocalized with macrophage staining in spleen and inguinal lymph node. | 0.5 mg/kg IV, 24 h; SI Figs. S12-S13. Qualitative localization, not a universal cell transfection percentage. |
Stability and biological interpretation
| Finding | Evidence boundary |
|---|---|
| 63-week formulated-LNP study at 4°C | SI Fig. S2 compares size, encapsulation, RNA integrity and cell-free translation. It is not a shelf-life study of neat nor-MC3. |
| Protein adsorption | The liposomal formulation adsorbed less total plasma protein than the comparator; main Fig. 3. Mechanistic association does not by itself prove clinical benefit. |
| Tolerability | The paper discusses expected tolerability using lipid-dose and liposome precedents. This is not a dedicated nor-MC3 repeated-dose toxicology study. No blanket nontoxic statement is assigned. |
Original study figures
Original cell and mouse figures in the publisher article — Original source figures.
References and source locations
- Cheng MHY et al. Liposomal lipid nanoparticles for extrahepatic delivery of mRNA. Nature Communications 16, 4135 (2025). DOI: 10.1038/s41467-025-58523-w.
- Supporting Information: Table S1 and Figures S2-S13.
- Related reference: Arnold D et al. nor-MC3 and nor-KC2: cationic ionizable lipids for the delivery of therapeutic nucleic acids. RSC Pharmaceutics 3, 654-658 (2026). DOI: 10.1039/D5PM00350D.
| CAS No. | Not available |
| Chemical Name | nor-MC3 |
| Synonyms | norMC3， nor MC3 |
| SMILES | CCCCC/C=C\C/C=C\CCCCCCCC(CCCCCCC/C=C\C/C=C\CCCCC)OC(=O)CCCN(C)C |
| Formula | C41H75O2N |
| M.Wt | 614.06 |
| Purity | >95% by ELSD-HPLC |
| 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 |
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