nor-MC3

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.

Total lipid (µmol)

Component	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.