Synthesis of hyperbranched amphiphilic polyester and theranostic nanoparticles thereof
A method of making a hyperbranched amphiphilic polyester compound includes drying under vacuum a mixture of 2-(4-hydroxybutyl)-malonic acid and p-toluene sulphonic acid as catalyst. The vacuum is then released with a dry inert gas after drying. The dried mixture is heated under the inert gas at a temperature sufficient for polymerization. The inert gas is evacuated while continuing to heat the mixture. The formed polymer is then dissolved in dimethylformamide and precipitated out by adding methanol. Modifications of the method yield nanoparticles of polyesters having properties suited for coencapsulating fluorescent dyes together with therapeutic drugs, resulting in theranostic nanoparticles, that is, nanoparticles useful in both therapeutic treatments and diagnostic methods.
1. A polymer comprising the repeating unit:
2. A polymeric nanoparticle comprising the polymer of claim 1 .
3. The polymeric nanoparticle of claim 2 , wherein the polymeric nanoparticle is biodegradable.
4. The polymeric nanoparticle of claim 2 , having one or more internal hydrophobic pockets and a hydrophilic outer surface.
5. The polymeric nanoparticle of claim 2 , having an average diameter of 115±25 nm.
6. The polymeric nanoparticle of claim 2 , being spherical in shape.
7. The polymeric nanoparticle of claim 2 , having a positive zeta potential.
8. The polymeric nanoparticle of claim 2 , further comprising a hydrophobic near-infrared fluorescent dye encapsulated therein.
9. The polymeric nanoparticle of claim 8 , wherein the dye is selected from the group consisting of DiI, DiR, DiD, and combinations thereof.
10. The polymeric nanoparticle of claim 2 , further comprising one or more therapeutic drugs encapsulated therein.
11. The polymeric nanoparticle of claim 10 , wherein the therapeutic drug comprises an anti-cancer drug.
12. The polymeric nanoparticle of claim 10 , wherein the therapeutic drug comprises azidothymidine.
13. The polymeric nanoparticle of claim 10 , wherein the therapeutic drug comprises paclitaxel.
14. The polymeric nanoparticle of claim 10 , further comprising a fluorescent dye co-encapsulated with said therapeutic drug.
15. The polymeric nanoparticle of claim 2 , further comprising a targeting ligand.
16. The polymeric nanoparticle of claim 2 , further comprising folate.
17. An aqueous suspension of the polymeric nanoparticle of claim 2 .
18. The aqueous suspension of claim 17 , further comprising a hydrophobic near-infrared fluorescent dye.
19. The aqueous suspension of claim 17 , further comprising a therapeutic drug.
20. The aqueous suspension of claim 17 , further comprising a hydrophobic near-infrared fluorescent dye and a therapeutic drug.
21. A method of functionalizing a nanoparticle, comprising:
contacting the nanoparticle of claim 10 with an azide-functionalized folic acid.