Nucleic acid functionalized nanoparticles for therapeutic applications
Materials and methods for modulating cellular uptake of functionalized nanoparticles are provided. Also provided are materials and methods for modulating the effectiveness of a therapeutic agent with a functionalized nanoparticle.
1. A method of modulating effectiveness of an anticancer drug comprising the step of:
administering said anticancer drug concomitantly with an oligonucleotide-functionalized nanoparticle, wherein said oligonucleotide-functionalized nanoparticle comprises an oligonucleotide comprising a sequence that modulates the effectiveness of said anticancer drug, and wherein the nanoparticle does not comprise a targeting agent.
2. The method of claim 1 wherein cellular localization of the anticancer drug is controlled by the oligonucleotide-functionalized nanoparticle.
3. The method of claim 1 wherein the oligonucleotide sequence is a chemosensitizing antisense sequence.
4. The method of claim 3 wherein the chemosensitizing antisense sequence increases the toxicity of the anticancer drug.
5. The method of claim 1 wherein the nanoparticle is non-metallic.
6. The method of claim 1 wherein the nanoparticle is metallic.
7. The method of claim 6 wherein the nanoparticle comprises gold, silver, platinum, aluminum, palladium, copper, cobalt, indium, or nickel.
8. The method of claim 1 wherein the effectiveness of the anticancer drug is altered by at least 10%, or at least 15%, or at least 20%, or at least 25%, or at least 30%, or at least 40%, or at least 50%, or at least 60%, or at least 70%, at least 80%, at least 90%, at least 95%, at least 2-fold, at least 5-fold, at least 10-fold, at least 20-fold, at least 50-fold or more compared to effectiveness of the anticancer drug in the absence of the oligonucleotide-functionalized nanoparticle.
9. The method of claim 1 wherein the oligonucleotide is from about 5 to about 100 nucleotides in length.
10. The method of claim 1 wherein the nanoparticle is from about 5 nanometers (nm) to about 50 nm in mean diameter.
11. The method of claim 1 wherein at least 20 oligonucleotides are functionalized to the nanoparticle.
12. The method of claim 1 wherein density of oligonucleotide on the surface of the nanoparticle is from about 1.5 pmol/cm 2 to about 25 pmol/cm 2 .
13. The method of claim 1 wherein density of oligonucleotide on the surface of the nanoparticle is about 4 pmol/cm 2 .
14. The method of claim 1 wherein the oligonucleotide is attached to the nanoparticle through a spacer.
15. The method of claim 1 wherein the oligonucleotide is a DNA oligonucleotide or a RNA oligonucleotide.
16. The method of claim 1 wherein the oligonucleotide-functionalized nanoparticle is associated with the anticancer drug.