Method and composition for targeted delivery of therapeutic agents

Abstract

Functionalized single walled or multi-walled carbon nanotubes (f-CNTs) can be delivered into mammals to targeted organs, such as the kidney and the liver. These f-CNTs may be non-covalently linked or covalently linked to therapeutic agents. In particular, the application delivers carbon nanotube-therapeutic agent conjugates to a target organ, thereby preventing or reducing damages to the organ caused by other agents or procedure.

1 . A method for preventing or reducing kidney or liver injury in a subject, comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising (1) one or more therapeutic nucleic acids conjugated to functionalized carbon nanotubes (f-CNTs) and (2) a pharmaceutically acceptable carrier, wherein said one or more therapeutic nucleic acids inhibit expression of one or more genes selected from the group consisting of MMP-9, JNK, Epas1, Hifl1an, Ac1, Fih1, Irp1, Egln1, Egln2, Egln3, PHD1, PHD2, PHD3, CTR1, CTR2, cFOS, FOS, cJUN, JUN, Fra1, Fra2, ATP, AP-1, MEP1A, MEP1B, VIM, p53, FASR, FASL, COL3A1, Kim-1 and C3 gene. 
     
     
         2 . The method of  claim 1 , wherein said kidney or liver injury includes injuries caused by hepatic toxins, nephrotoxins and ischemia. 
     
     
         3 . The method of  claim 1 , wherein said kidney injury is acute kidney injury. 
     
     
         4 . The method of  claim 1 , wherein the one or more therapeutic nucleic acids are therapeutic RNAs that are non-covalently linked to the f-CNTs. 
     
     
         5 . The method of  claim 1 , wherein the one or more therapeutic nucleic acids are therapeutic RNAs that are covalently linked to the f-CNTs. 
     
     
         6 . The method of  claim 1 , wherein the f-CNTs are functionalized single walled carbon nanotubes (f-SWCNTs). 
     
     
         7 . The method of  claim 1 , wherein the f-CNTs are functionalized multi-walled carbon nanotubes. 
     
     
         8 . The method of  claim 1 , wherein the f-CNTs are replaced by any fibrillary molecule with an aspect ratio greater than 1. 
     
     
         9 . The method of  claim 1 , wherein the pharmaceutical composition is prophylactically administered before the occurrence of kidney or liver injury. 
     
     
         10 . The method of  claim 1 , wherein the pharmaceutical composition is administered after the occurrence of kidney or liver injury. 
     
     
         11 . The method of  claim 1 , wherein the one or more therapeutic nucleic acids are selected from the group consisting of siRNAs, miRNA precursors, single-stranded mature miRNAs, double-stranded mature miRNAs and antisense RNAs, synthetic modified RNA, DNA, and synthetic modified DNA. 
     
     
         12 . The method of  claim 1 , wherein the one or more therapeutic RNAs comprise an siRNA. 
     
     
         13 . The method of  claim 1 , wherein the therapeutic RNAs comprise siRNAs that inhibit expression of p53 and MEP1B genes. 
     
     
         14 . A pharmaceutical composition for preventing or reducing kidney and/or liver injury, comprising (1) one or more therapeutic RNAs conjugated to functionalized carbon nanotubes (f-CNTs) and (2) a pharmaceutically acceptable carrier, wherein the one or more RNA inhibit expression of one or more genes selected from the group consisting of MMP-9, JNK, Epas1, Hifl1an, Ac1, Fih1, Irp1, Egln1, Egln2, Egln3, PHD1, PHD2, PHD3, CTR1, CTR2, cFOS, FOS, cJUN, JUN, Fra1, Fra2, ATP, AP-1, MEP1A, MEP1B, VIM, p53, FASR, FASL, COL3A1, Kim-1 and C3 gene. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the one or more therapeutic RNAs are non-covalently linked to the f-CNTs. 
     
     
         16 . The pharmaceutical composition of  claim 14 , wherein the one or more therapeutic RNAs are covalently linked to the f-CNTs. 
     
     
         17 . The pharmaceutical composition of  claim 14 , wherein the f-CNTs are functionalized single walled carbon nanotubes (f-SWCNTs). 
     
     
         18 . The pharmaceutical composition of  claim 14 , wherein the one or more therapeutic RNAs are selected from the group consisting of siRNAs, miRNA precursors, single-stranded mature miRNAs, double-stranded mature miRNAs and antisense RNAs. 
     
     
         19 . The pharmaceutical composition of  claim 14 , wherein the one or more therapeutic RNAs comprise an siRNA. 
     
     
         20 . The pharmaceutical composition of  claim 14 , wherein the therapeutic RNAs comprise siRNAs that inhibit expression of p53 and MEP1B genes. 
     
     
         21 . A method for reducing acute kidney injury in a subject, comprising administering to the subject an effective amount of a pharmaceutical composition, comprising: (1) one or more siRNAs conjugated to functionalized single wall carbon nanotubes (f-SWCNTs); and (2) a pharmaceutically acceptable carrier, wherein the one or more siRNAs inhibit expression of one or more genes selected from the group consisting of MMP-9, JNK, Epas1, Hifl1an, Ac1, Fih1, Irp1, Egln1, Egln2, Egln3, PHD1, PHD2, PHD3, CTR1, CTR2, cFOS, FOS, cJUN, JUN, Fra1, Fra2, ATP, AP-1, MEP1A, MEP1B, VIM, p53, FASR, FASL, COL3A1, Kim-1 and C3 gene. 
     
     
         22 . The method of  claim 21 , wherein the one or more siRNAs are non-covalently linked to the f-SWCNTs.