Multimodal, multifunctional polymer coated nanoparticles
View Patent ↗Disclosed are nanoparticles having a metallic core consisting essentially of superparamagnetic iron oxide; a polymeric coat surrounding said core, the coat having a matrix of polyacrylic acid and forming an outer periphery of said nanoparticle; a plurality of hydrophobic pockets formed by the polymeric coat; a plurality of carboxylic groups along an outer periphery of the polymeric coat and effective to conjugate with a predetermined targeting ligand which functionalizes the nanoparticle; a lipophylic fluorescent dye encapsulated in the plurality of hydrophobic pockets; and a drug encapsulated in the plurality of hydrophobic pockets. Associated methods of making the nanoparticles and of treatments using the nanoparticles are also disclosed.
1. A nanoparticle comprising:
a metallic core;
a polymeric coat surrounding said core and forming an outer periphery of said nanoparticle;
a plurality of hydrophobic pockets formed by the polymeric coat;
a plurality of carboxylic groups along an outer periphery of the polymeric coat and effective to conjugate with a predetermined targeting ligand which functionalizes the nanoparticle;
a lipophilic fluorescent dye encapsulated in the plurality of hydrophobic pockets; and
a drug encapsulated in the plurality of hydrophobic pockets.
2. The nanoparticle of claim 1 , wherein the metallic core comprises a metallic oxide.
3. The nanoparticle of claim 1 , wherein the metallic core comprises superparamagnetic iron oxide.
4. The nanoparticle of claim 1 , wherein said polymeric coat comprises a biodegradable polymer.
5. The nanoparticle of claim 1 , wherein said polymeric coat comprises a matrix of polyacrylic acid.
6. The nanoparticle of claim 1 , wherein said polymeric coat comprises a biodegradable polymer effective for forming a plurality of hydrophobic pockets.
7. The nanoparticle of claim 1 , wherein folate groups are conjugated to the polymeric coat.
8. The nanoparticle of claim 1 , wherein folate groups are conjugated to a plurality of carboxylic groups on the polymeric coat.
9. The nanoparticle of claim 1 , wherein azide-functionalized folate groups are conjugated to the polymeric coat.
10. The nanoparticle of claim 1 , wherein azide-functionalized folate groups are conjugated to the plurality of carboxylic groups on the polymeric coat.
11. The nanoparticle of claim 1 , wherein the lipophilic fluorescent dye is selected from the group consisting of dialkylcarbocyanine fluorescent dyes.
12. The nanoparticle of claim 1 , wherein the lipophylic fluorescent dye is selected from lipophilic dyes having a near-infrared spectrum.
13. The nanoparticle of claim 1 , wherein the lipophilic fluorescent dye is selected from DiI, DiR and 4′,6-diamidino-2-phenylindole.
14. The nanoparticle of claim 1 , wherein the drug comprises a hydrophobic or lipophilic moiety.
15. The nanoparticle of claim 1 , wherein the drug comprises a hydrophobic moiety.
16. The nanoparticle of claim 1 , wherein the drug is an anti-cancer therapeutic drug.
17. The nanoparticle of claim 1 , wherein the drug is paclitaxel.
18. The nanoparticle of claim 1 , wherein the lipophylic fluorescent dye and the drug are co-encapsulated in the plurality of hydrophobic pockets.
19. A method of treatment comprising contacting a cancerous cell with the nanoparticle of claim 1 which has been conjugated with a ligand specific for a receptor expressed by the cancerous cell and wherein the drug is an anti-cancer drug.
20. The method of claim 19 , further comprising tracking the nanoparticle by magnetic resonance imaging.
21. The method of claim 19 , further comprising tracking the nanoparticle by optical imaging relying on fluorescence.
22. A method of treatment comprising contacting a diseased cell with the nanoparticle of claim 1 which has been conjugated with a ligand specific for a receptor expressed by the diseased cell and wherein the drug is effective for treating the disease afflicting the cell.
23. The method of claim 22 , further comprising tracking the nanoparticle by magnetic resonance imaging.
24. The method of claim 22 , further comprising tracking the nanoparticle by optical imaging relying on fluorescence.
25. A water based, step-wise method of making polyacrylic acid-coated iron oxide nanoparticles of claim 1 , the method comprising:
preparing an aqueous solution of iron salts by mixing FeCl3 and FeCl2 in dilute hydrochloric acid;
preparing an alkaline solution by dissolving ammonium hydroxide in deionized water purged with nitrogen gas;
preparing a coating agent solution by dissolving polyacrylic acid in deionized water;
reacting by mixing the iron salts solution with the alkaline solution while vigorously stirring the mixture to form a dark suspension of iron oxide nanoparticles;
adding coating agent solution while stirring;
separating the iron oxide nanoparticles from the suspension;
washing the separated nanoparticles in water to minimize free polyacrylic acid and other unreacted reagents;
purifying the washed nanoparticles through a magnetic column; and
concentrating the purified nanoparticles.
26. A method of making polyacrylic acid-coated iron oxide nanoparticles of claim 1 , the method comprising:
reacting an acidic solution containing Fe+2 and Fe+3 ions with aqueous ammonium hydroxide to form a dark suspension of iron oxide nanoparticles;
mixing aqueous polyacrylic acid with the suspension of iron oxide nanoparticles while stirring for a time sufficient for the nanoparticles to become coated with the polyacrylic acid;
separating coated iron oxide nanoparticles from the mixture; and
washing and concentrating the separated nanoparticles.