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 preparing a stealth nanoparticle having a ratio of ligand-bound polymer to non-functionalized polymer effective for the treatment of prostate cancer, comprising the steps of: (a) providing an anti-cancer agent; (b) providing a first polymer; (c) providing a low-molecular weight PSMA ligand; (d) reacting the first polymer with the low-molecular weight PSMA ligand to form a ligand-bound polymer; and (e) mixing the ligand-bound polymer with a second polymer, wherein the second polymer is non-functionalized, and the anti-cancer agent, thereby forming the stealth nanoparticle,
wherein the ligand-bound polymer is:
wherein
R 1 and R 3 are alkyl groups;
R 2 is an ester group or amide linkage;
X+Y=20 to 1720; and
Z=25 to 455.
2. The method of claim 1 , wherein the second polymer comprises a block copolymer of two or more polymers.
3. The method of claim 2 , wherein the second polymer is a diblock copolymer of (i) PLGA and PEG or (ii) PLA and PEG.
4. The method of claim 1 , wherein the anti-cancer agent is selected from the group consisting of paclitaxel, docetaxel, mitoxandrone, doxorubicin, gemcitabine, 5-fluorouracil, daunorubicin or 9-dihydrotaxol.
5. The method of claim 4 , wherein the anti-cancer agent is paclitaxel, docetaxel or dihydrotaxol.
6. The method of claim 1 , wherein the nanoparticle has a diameter of 80 nm to 200 nm.