Nanoparticle drug conjugates

Abstract

Described herein are nanoparticle drug conjugates (NDCs), which, in certain embodiments, comprise a non-toxic, multi-modality, clinically proven silica-based nanoparticle platform with covalently attached drug molecules/moieties. The nanoparticle drug conjugates (NDCs) demonstrate imaging capability and targeting ligands which efficiently clear through the kidneys. Furthermore, the conjugates incorporate therapeutic agents for cancer detection, prevention, and/or treatment.

1 - 19 . (canceled) 
     
     
         20 . A nanoparticle drug conjugate (NDC) comprising:
 a nanoparticle having an average diameter from 5 nm to 10 nm that comprises a silica-based core and a silica shell surrounding a least a portion of the core;   a linker moiety;   a drug moiety; and   one or more targeting moieties,   wherein the surface of the nanoparticle is covalently modified with polyethylene glycol groups, and   wherein the drug moiety and linker moiety form a cleavable linker-drug construct that is covalently linked to the nanoparticle.   
     
     
         21 . The NDC of  claim 20 , wherein the linker moiety is enzyme sensitive. 
     
     
         22 . The NDC of  claim 21 , wherein the linker moiety is capable of undergoing hydrolysis at the C-terminal end upon protease binding, thereby releasing the drug moiety from the nanoparticle. 
     
     
         23 . The NDC of  claim 22 , wherein the protease comprises a serine protease or a cysteine protease. 
     
     
         24 . The NDC of  claim 22 , wherein the average drug moiety to nanoparticle ratio ranges from 1 to 20. 
     
     
         25 . The NDC of  claim 20 , comprising from 1 to 20 targeting moieties. 
     
     
         26 . The NDC of  claim 20 , wherein the targeting moieties bind to receptors on tumor cells. 
     
     
         27 . The NDC of  claim 20 , further comprising a fluorescent compound. 
     
     
         28 . The NDC of  claim 27 , wherein the fluorescent compound is Cy5.5. 
     
     
         29 . The NDC of  claim 20 , wherein the nanoparticle is an organo-silica core shell nanoparticle. 
     
     
         30 . A method of treating of cancer comprising administering a nanoparticle drug conjugate (NDC) comprising:
 a nanoparticle having an average diameter from 5 nm to 10 nm that comprises a silica-based core and a silica shell surrounding a least a portion of the core;   a linker moiety;   a drug moiety; and   one or more targeting moieties,   wherein the surface of the nanoparticle is covalently modified with polyethylene glycol groups, and   wherein the drug moiety and linker moiety form a cleavable linker-drug construct that is covalently linked to the nanoparticle.