Cancer cell targeting using nanoparticles
The present invention generally relates to polymers and macromolecules, in particular, to polymers useful in particles such as nanoparticles. One aspect of the invention is directed to a method of developing nanoparticles with desired properties. In one set of embodiments, the method includes producing libraries of nanoparticles having highly controlled properties, which can be formed by mixing together two or more macromolecules in different ratios. One or more of the macromolecules may be a polymeric conjugate of a moiety to a biocompatible polymer. In some cases, the nanoparticle may contain a drug. Other aspects of the invention are directed to methods using nanoparticle libraries.
1. A method of treating a solid tumor cancer in a subject in need thereof comprising systemically administering a therapeutically effective amount of nanoparticles comprising:
a chemotherapeutic agent;
a diblock copolymer of poly (ethylene)glycol and polylactic acid; and
a ligand conjugate comprising:
wherein
R 1 and R 3 are alkyl groups;
R 2 is an ester or amide linkage;
X+Y=20 to 1720; and
Z=25 to 455.
2. The method of claim 1 , wherein the particles are administered by parenteral administration.
3. The method of claim 2 , wherein the parenteral administration is intravenous or subcutaneous administration.
4. The method of claim 3 , wherein the solid tumor cancer is prostate cancer.
5. The method of claim 1 , wherein the solid tumor cancer is non-small cell lung cancer.
6. The method of claim 1 , wherein the chemotherapeutic agent is docetaxel.
7. The method of claim 4 , wherein the chemotherapeutic agent is docetaxel.
8. The method of claim 1 , wherein the ligand conjugate is a prostate specific membrane antigen ligand conjugate comprising:
wherein R 1 and R 3 are alkyl groups, R 2 is an ester or amide linkage, x+y=20 to 1720, and z=25 to 455.
9. The method of claim 1 , wherein the nanoparticles have a diameter of 80 nm to 200 nm.
10. The method of claim 1 wherein the solid tumor cancer is a prostate cancer or non-prostate cancer.
11. The method of claim 1 wherein the cancer is colorectal carcinoma or glioblastoma.