Lipid nanoparticles and uses thereof
The present invention relates to lipid-associated indocyanine green particles for enhanced functional high-resolution near-infrared fluorescence medical imaging of lymphatic vessels, lymph nodes, lymphatic abnormalities, tumors, and inflammation.
1. A composition, comprising:
(i) a lipid nanoparticle comprising a lipid membrane; and
(ii) a plurality of indocyanine green (ICG) molecules,
wherein at least 95% of said ICG molecules are embedded in said lipid membrane, wherein said nanoparticle has an average size of 50 nm to 100 nm.
2. The composition of claim 1 , wherein said lipid membrane comprises 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- methoxy-polyethylene glycol-2000 (DSPEmPEG2000).
3. The composition of claim 1 , wherein at least 99% of said ICG is embedded in said lipid membrane.
4. The composition of claim 1 , wherein substantially 100% of said ICG is embedded in said lipid membrane.
5. The composition of claim 1 , wherein said lipid nanoparticle is suspended in a biocompatible buffer that has a pH 5-8 and Osm ˜303 mOSM.
6. The composition of claim 1 , wherein said nanoparticle has an average size of 50 nm to 80 nm.
7. The composition of claim 1 , wherein said nanoparticle has a negative surface charge.
8. The composition of claim 1 , wherein said nanoparticle is stable in serum with between 90%, to 100% of its initial fluorescence retained in heat-inactivated-serum after 6 h, at 25° C.
9. The composition of claim 1 , wherein said nanoparticle has a fluorescence intensity between 4- and 5-fold higher than that of free ICG in aqueous solution.
10. The composition of claim 1 , wherein said nanoparticle has a fluorescence intensity between 4- and 100,000-fold higher than that of free ICG in aqueous solution after being stored at 4° C for between 0 and 300 days.
11. The composition of claim 1 , wherein said composition is potent at less than 0.5 mg/kg body weight ICG dose.
12. The composition of claim 1 , wherein said composition is potent at 0.01 mg/kg body weight ICG dose.
13. A method for imaging a tissue or organ in a subject, comprising: administering to a subject in need of imaging a suitable amount of the composition of claim 1 , and obtaining an image of a tissue or organ of said subject.
14. The method of claim 13 , wherein the amount of the composition equals an ICG dose of between about 0.01 mg/kg body weight to about 0.5 mg/kg body weight.
15. The method of claim 13 , wherein said tissue or organ is selected from the group consisting of: Lymphatic vessels, Secondary lymphoid tissues, Blood vessels, Endothelial lesions, Tumors, Tertiary lymphoid tissues, Liver, Bile duct, Gall bladder, Intestine, Stomach, Brain, Breast, Lung, Heart, Eye, Ovarian, Prostate.
16. The method of claim 13 , wherein the administration route for said composition is selected from the group consisting of systemic and local administrations.
17. The method of claim 16 , wherein the systemic administration comprises intravascular injection.
18. The method of claim 16 , wherein the local administration comprises subcutaneous injection, intradermal injection, submucous injection, subserous injection, intramuscular injection, oral administration, intranasal administration or intra- and peri-tumoral injection.
19. The method of claim 18 , wherein the amount of the composition at single injection site equals an ICG dose between 0.1 ng and 0.1 mg.