Cabazitaxel-platinum nanoparticles and methods of using same
The present teachings relate to compounds and compositions for treatment of cancers. In some embodiments, the composition comprises a platinum compound having a heterocycle ligand. Cabazitaxel-platinum nanoparticles are disclosed herein, as well as methods of making and using the same.
1. A nanoparticle comprising:
(a) a conjugate comprising
A-Y—Pt
wherein:
Y is a linker;
Pt is a platinum complex; and
A is cabazitaxel, a cabazitaxel analogue or a derivative thereof; and
(b) a base component.
2. The conjugate of claim 1 , wherein Y is selected from the group consisting of: C 1 -C 10 straight chain alkyl, C 1 -C 10 straight chain O-alkyl, C 1 -C 10 straight chain substituted alkyl, C 1 -C 10 straight chain substituted O-alkyl, C 4 -C 13 branched chain alkyl, C 4 -C 13 branched chain O-alkyl, C 2 -C 12 straight chain alkenyl, C 2 -C 12 straight chain O-alkenyl, C 3 -C 12 straight chain substituted alkenyl, C 3 -C 12 straight chain substituted O-alkenyl, polyethylene glycol, polylactic acid, polyglycolic acid, poly(lactide-co-glycolide), polycarprolactone, polycyanoacrylate, ketone, aryl, heterocyclic, succinic ester, amino acid, aromatic group, ether, crown ether, urea, thiourea, amide, purine, pyrimidine, bypiridine, indole derivative acting as a cross linker, chelator, aldehyde, ketone, bisamine, bis alcohol, heterocyclic ring structure, azirine, disulfide, thioether, hydrazone, and combinations thereof.
3. The nanoparticle of claim 1 wherein Y is selected from the group consisting of: a C 3 straight chain alkyl and a ketone.
4. The nanoparticle of claim 1 , wherein the conjugate is encapsulated in, tethered to, or associated with the nanoparticle.
5. The nanoparticle of claim 1 , wherein the based component is selected from the group consisting of: a polymer, a small molecule, and a mixture thereof.
6. The nanoparticle of claim 5 , wherein the nanoparticle may contain a plurality of the same or different conjugates.
7. The nanoparticle of claim 1 , wherein the conjugate is a compound of formula II:
8. A method of killing a cancer cell, the method comprising contacting a cancer cell with an effective amount of a nanoparticle of claim 1 .
9. The method of claim 8 , wherein the cancer cell is a prostate cancer cell.
10. A method of treating cancer wherein the cancer is prostate cancer, the method comprising identifying a subject at risk for or diagnosed with prostate cancer and administering a therapeutically effective amount of a nanoparticle of claim 1 .
11. The nanoparticle of claim 5 , wherein the base component is a polymer comprising polydioxanone (PDO), polyhydroxyalkanoate, polyhydroxybutyrate, poly(glycerol sebacate, polyglycolide, poly(lactic acid) (PLA), polycaprolactone, polylactide, polyglycolide, poly(ortho esters), poly(caprolactones), polylysine, poly(ethylene imine), poly(acrylic acid), poly(urethanes), poly(anhydrides), poly(esters), poly(trimethylene carbonate), poly(beta amino esters), poly(alkylene glycol), or copolymers or derivatives thereof.
12. The nanoparticle of claim 11 , wherein the base component is a polymer comprising poly(lactic acid) (PLA), poly(ethylene glycol) (PEG) or copolymers or derivatives thereof.
13. The nanoparticle of claim 5 , wherein the base component is a small molecule comprising a lipid.