Carrier Nanoparticles And Related Compositions, Methods And Systems

Abstract

Carrier nanoparticles comprising a polymer containing a polyol coupled to a polymer containing a boronic acid and a linkage cleavable under reducing conditions, configured to present the polymer containing a boronic acid to an environment external to the nanoparticle and related compositions, methods and systems.

What is claimed is: 
     
         1 . A nanoparticle comprising a polymer containing a polyol comprising one or more of at least one of the following structural units of Formula (I), (II), or (III): 
       
         
           
           
               
               
           
         
         wherein:
 A comprises a polyol having 4 or 6 adjacent hydroxyl groups; and 
 B comprises a neutral, cationic, or anionic organic moiety having a chemical backbone comprising —C m H 2m — linkages, where m≥1, and optionally one or more:
 (a) polyglycol linkage, —(CH 2 —CH 2 —O) p —, in the chemical backbone, where p is from 20 to 200; and/or 
 (b) amidinium, quaternary ammonium, or imidazolium functional group in the chemical backbone; and/or 
 (c) sulfonate, nitrate, carboxylate, phosphonate, or primary or secondary amine bonded to the chemical backbone; and 
 wherein A and B are covalently linked by amide or ester linkages. 
 
 
       
     
     
         2 . The nanoparticle of  claim 1 , wherein A comprises glucose, fructose, mannitol, sucrose, galactose, sorbitol, xylose, galactose, or mucic acid. 
     
     
         3 . The nanoparticle of  claim 1 , wherein A comprises mucic acid. 
     
     
         4 . The nanoparticle of  claim 1 , wherein A further comprises a polyglycol linkage, —(CH 2 —CH 2 —O) n —, where n is from 1 to 20 
     
     
         5 . The nanoparticle of  claim 1 , wherein B comprises an amidinium, quaternary ammonium, or imidazolium functional group in the chemical backbone. 
     
     
         6 . The nanoparticle of  claim 1 , wherein B comprises a sulfonate, nitrate, carboxylate, phosphonate, or primary or secondary bonded to the chemical backbone. 
     
     
         7 . The nanoparticle of  claim 1 , wherein the polymer containing the polyol is derived from the coupling of a compound: 
       
         
           
           
               
               
           
         
         with a compound of: 
       
       
         
           
           
               
               
           
         
         wherein n, q, and p are independently 1-20. 
       
     
     
         8 . The nanoparticle of  claim 1 , wherein the polymer containing the polyol comprises a structural unit of: 
       
         
           
           
               
               
           
         
         wherein n is 1-20. 
       
     
     
         9 . The nanoparticle of  claim 1 , comprising a structural unit of: 
       
         
           
           
               
               
           
         
       
     
     
         10 . The nanoparticle of  claim 1 , comprising a structural unit of: 
       
         
           
           
               
               
           
         
       
     
     
         11 . The nanoparticle of  claim 1 , further comprising one or more targeting ligand molecules per nanoparticle, each one or more targeting ligand molecules bonded to the nanoparticle via a linker comprising at least one of an amide, a borate ester, carboxylate ester, or a disulfide linkage. 
     
     
         12 . The nanoparticle of  claim 11 , wherein the one or more targeting ligand molecule per nanoparticle comprises a ligand for a cellular receptor, a cellular receptor protein, a ligand for a cellular receptor, or cellular receptor protein. 
     
     
         13 . The nanoparticle of  claim 11 , wherein the one or more targeting ligand molecule per nanoparticle comprises a vitamin, a protein, a protein fragment, a monosaccharide, a peptide, a peptide aptamer, an oligopeptide, a polypeptide or fragment thereof, a polysaccharide, a polynucleotide, an antibody, or an antibody fragment. 
     
     
         14 . The polymer conjugate of  claim 11 , wherein the one or more targeting ligand molecule per nanoparticle comprises an antibody or antibody fragment against a surface cell receptor. 
     
     
         15 . The nanoparticle of  claim 11 , wherein the one or more targeting ligand molecule per nanoparticle comprises transferrin, folic acid, or galactose 
     
     
         16 . The nanoparticle of  claim 1 , further comprising at least one therapeutic agent incorporated therein or coupled thereto. 
     
     
         17 . The nanoparticle of  claim 16 , wherein the at least one therapeutic agent comprises a chemotherapeutic agent. 
     
     
         18 . The nanoparticle of  claim 16 , wherein the at least one therapeutic agent comprises an epothilone, a camptothecin-based drug, doxorubicin, taxol, or a nucleic acid, or a combination thereof 
     
     
         19 . The nanoparticle of  claim 16 , wherein the at least one therapeutic agent comprises camptothecin, an epothilone, a taxane or a combination thereof. 
     
     
         20 . The nanoparticle of  claim 16 , wherein at least one therapeutic agent comprises a plasmid, a genomic DNA, siRNA, shRNA, miRNA, antisense oligonucleotide, a chimeric nucleotide, an aptamer, or a combination thereof. 
     
     
         21 . The nanoparticle of  claim 1 , further comprising:
 (a) at least one targeting ligand molecule per nanoparticle, wherein each targeting ligand molecule is bonded to the nanoparticle via a linkage comprising at least one of an amide, a borate ester, carboxylate ester, or a disulfide linkage, wherein the at least one targeting ligand molecule comprises a ligand for a cellular receptor, a cellular receptor protein, a ligand for a cellular receptor, or cellular receptor protein; and   (b) at least one therapeutic agent.   
     
     
         22 . The nanoparticle of  claim 21 , wherein:
 (a) the polymer containing the polyol comprises a structural unit of:   
       
         
           
           
               
               
           
         
       
       wherein n is 1-20;
 (b) the targeting ligand molecule is transferrin, and 
 (c) the therapeutic agent comprises camptothecin and an optional antibody. 
 
     
     
         23 . An aqueous solution comprising a plurality of nanoparticles of  claim 1 . 
     
     
         24 . An aqueous solution comprising a plurality of nanoparticles of  claim 21 . 
     
     
         25 . A method of treating a functional disorder in a human patient's body, the method comprising administering to the human patient a plurality of nanoparticles of  claim 21 . 
     
     
         26 . The method of  claim 25 , wherein the functional disorder is a mental disorder. 
     
     
         27 . The method of  claim 25 , wherein the functional disorder is a physical disorder. 
     
     
         28 . The method of  claim 25 , wherein the functional disorder is a cancer and the therapeutic agent is at least one chemotherapeutic agent. 
     
     
         29 . The method of  claim 25 , wherein:
 (a) the functional disorder is a cancer,   (b) the nanoparticles comprise polymer containing the polyol comprising a structural unit of:   
       
         
           
           
               
               
           
         
       
       wherein n is 1-20;
 (c) the targeting ligand molecule is transferrin, and 
 (d) the therapeutic agent comprises camptothecin and an optional antibody.