Lipid Selection Shapes LNP Performance

Lipid composition and ratios are critical determinants of LNP performance, influencing cellular uptake, endosomal escape, biodistribution and tissue targeting. Selecting the right lipid components can therefore play a key role in optimising RNA delivery for your research application.

Explore selected lipids for passive organ targeting, enhanced cellular delivery and active tumor targeting beyond the liver, the predominant destination of many systemically administered LNPs.

 

Find the right lipid for your targeting strategy

Select your targeting approach and biological destination to explore relevant lipid options.

1
Targeting strategy

What is your objective?

2
Organ

Where do you want to target?

Suggested options

Lipids for lung targeting

5 options

Passive targeting

Organ Lipid Evidence & targeting profile
Lung 113-N16B BP-44506 Shown to specifically target the lungs in mice following i.v. injection, mainly targeting endothelial cells and, to a lesser extent, macrophages and epithelial cells. Qiu et al., PNAS, 2022
306-N16B BP-40862 Shown to specifically target the lung in vivo following i.v. administration, with predominant targeting of endothelial cells.
CP-LC-1073 Developed to specifically target the lungs in mice following i.v. injection. Certest data – reference to be added
Lipid 35 Demonstrated high lung specificity, with little to no luciferase expression detected in the liver. Naidu et al., 2025 View publication →
DOTAP Inclusion of this cationic lipid in LNPs has been used to promote lung targeting as part of the SORT strategy. Cheng et al., Nature Nanotechnology, 2020
Spleen 18PA 1,2-distearoyl-sn-glycero-3-phosphate Inclusion of this lipid has been used to promote spleen targeting as part of the SORT strategy. Cheng et al., Nature Nanotechnology, 2020
CP-LC-1405 Developed to specifically target the spleen. Certest data – reference to be added
Brain NT1-O12B Demonstrated the ability to cross the blood–brain barrier and reach the brain in vivo following i.v. administration. Ma et al., Science Advances, 2020
NT1-O14B Demonstrated the ability to cross the blood–brain barrier and reach the brain in vivo following i.v. administration. Ma et al., Science Advances, 2020

Enhanced delivery

Lipid Function
DSPE-PEG-R8 Cell-penetrating peptide conjugates used to improve cellular uptake and transfection efficiency.
DSPE-PEG-TAT

Active targeting

Tumour targeting
Lipid Target receptor
DSPE-PEG-cRGD / iRGD Integrins, often overexpressed in different types of cancer.
DSPE-PEG-Folate Folate receptors
DSPE-PEG-T7 Transferrin receptors
DSPE-PEG-GE11 EGFR

*This selection is not exhaustive. Additional lipid options are available depending on your delivery strategy and research application. Contact us.

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Lipid composition can influence LNP biodistribution

While ionizable lipids play a central role in RNA delivery, other LNP components can also influence tissue targeting and biodistribution. For example, changes in PEG-lipids, phospholipids and cholesterol derivatives have been reported to alter LNP distribution across organs.

DSG-PEG has been associated with increased spleen uptake (Liu et al., Molecular Therapy – Nucleic Acids, 2025), while DPPC has been reported to enhance lung targeting (Sun et al., 2026) and DSPC to support spleen targeting (Suzuki et al., Journal of Controlled Release, 2025). Replacing cholesterol with DC-cholesterol can also substantially alter LNP biodistribution (Goo et al., Journal of Controlled Release, 2026).

Careful selection of lipid components and their relative proportions is therefore important when designing an LNP formulation for a specific delivery objective.

*Non-exhaustive list. For any other options, please contact us.

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