Nanoscale platinum compounds and methods of use thereof
The invention is directed to biocompatible conjugated polymer nanoparticles including a copolymer backbone, a plurality of sidechains covalently linked to said backbone, and a plurality of platinum compounds dissociably linked to said backbone. The invention is also directed to dicarbonyl-lipid compounds wherein a platinum compound is dissociably linked to the dicarbonyl compound. The invention is also directed to methods of treating cancer or metastasis. The methods includes selecting a subject in need of treatment for cancer or metastasis and administering to the subject an effective amount of any of the nanoparticles, compounds, or compositions of the invention.
1. A conjugate comprising:
a dicarbonyl molecule, wherein a platinum compound is dissociably linked to the dicarbonyl molecule; and
a lipid molecule, wherein the dicarbonyl molecule is covalently linked to the lipid molecule,
wherein the dicarbonyl molecule is R′OC(O)—R—C(O)—, wherein R is C 1 -C 6 alkylene,
wherein the alkylene can comprise one or more double or triple bonds and/or the backbone of the alkylene can be interrupted with one or more of O, S, S(O), SO 2 , NH, C(O); and R′ is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, acylcyl, heterocyclyl, each of which can be optionally substituted; and
wherein the platinum compound is dissociably linked to the dicarbonyl molecule by a monocarboxylato bond and a Pt<->O coordinate bond.
2. The conjugate of claim 1 , wherein the dicarbonyl molecule is succinic acid.
3. The conjugate of claim 1 , wherein the dicarbonyl molecule is covalently linked to the lipid molecule by a linker.
4. The conjugate of claim 1 , wherein said platinum compound is selected from Pt(II) compounds, Pt(IV) compounds, and any combinations thereof.
5. The conjugate of claim 4 , wherein said platinum compound is a Pt(II) compound selected from the group consisting of cisplatin, oxaliplatin, carboplatin, paraplatin, sartraplatin, and combinations thereof.
6. The conjugate of claim 1 , wherein the conjugate is:
7. The conjugate of claim 1 , wherein the conjugate is
8. A method of treating cancer or metastasis comprising: administering to a subject in need thereof an effective amount of a conjugate of claim 1 .