Targeted nanoparticles

Abstract

Described herein are carrier nanoparticles comprising a polymer containing a polyol coupled to a polymer containing a nitroboronic boronic acid and a linkage cleavable under reducing conditions, configured to present the polymer containing the nitroboronic acid to an environment external to the nanoparticle. Targeted versions of the described nanoparticles are also described, as are related compositions, methods and systems.

What is claimed: 
     
         1 . A nanoparticle comprising:
 (a) a first polymer containing a polyol coupled to a second polymer containing a phenylboronic acid;   (b) a ligand for a first cellular receptor; and   (c) a therapeutic agent.   
     
     
         2 . The nanoparticle of  claim 1  wherein, in the first polymer, the polyol is a mucic acid polymer (MAP). 
     
     
         3 . The nanoparticle of  claim 2 , wherein the mucic acid polymer contains repeating units comprising: 
       
         
           
           
               
               
           
         
       
       wherein:
 n is 1. 
 
     
     
         4 . The nanoparticle of  claim 3 , wherein the mucic acid polymer has the structural unit: 
       
         
           
           
               
               
           
         
       
       derived from the coupling of A and B; 
       wherein A is 
       
         
           
           
               
               
           
         
       
       Bis 
       
         
           
           
               
               
           
         
       
       and 
       wherein:
 sugar is mucic acid, 
 spacer is —CH 2 —CH 2 —NH—, 
 L is a leaving group, and 
 p is from 20-200. 
 
     
     
         5 . The nanoparticle of  claim 1  wherein, in the second polymer, the phenylboronic acid is a nitrophenylboronic acid. 
     
     
         6 . The nanoparticle of  claim 5 , wherein the second polymer has the structure: 
       
         
           
           
               
               
           
         
       
       and isomers thereof wherein:
 (a) the PEG moiety is attached to the phenyl ring in an ortho or a para position relative to the boronic acid moiety, and/or 
 (b) the nitro group is attached to the phenyl ring in an ortho or a para position relative to the boronic acid moiety; and 
 
       wherein s is from 20-300, and 
       functional group 2 comprises the ligand for a first cellular receptor. 
     
     
         7 . The nanoparticle of  claim 1 , wherein the ligand for a first cellular receptor is a protein. 
     
     
         8 . The nanoparticle of  claim 7 , wherein the protein is an antibody directed to the first cellular receptor. 
     
     
         9 . The nanoparticle of  claim 8 , wherein the antibody is Herceptin®. 
     
     
         10 . The nanoparticle of  claim 1 , wherein the therapeutic agent is a small molecule chemotherapeutic. 
     
     
         11 . The nanoparticle of  claim 10 , wherein the small molecule chemotherapeutic is selected from the group consisting of camptothecin, a camptothecin-based drug, an epothilone and a taxane. 
     
     
         12 . The nanoparticle of  claim 11 , wherein the small molecule chemotherapeutic is a camptothecin-based drug. 
     
     
         13 . The nanoparticle of  claim 10 , wherein the small molecule chemotherapeutic is attached to the first polymer through a biodegradable ester bond. 
     
     
         14 . The nanoparticle of  claim 1 , wherein:
 (a) the first polymer comprises a mucic acid-containing polymer coupled to a nitrophenylboronic acid-containing polymer;   (b) the ligand for a first cellular receptor is Herceptin®; and   (c) the therapeutic agent is a camptothecin-based drug.   
     
     
         15 . A pharmaceutical composition comprising the nanoparticle of  claim 1  and a pharmaceutically acceptable vehicle, excipient or diluent. 
     
     
         16 . A pharmaceutical composition comprising the nanoparticle of  claim 14  and a pharmaceutically acceptable vehicle, excipient or diluent. 
     
     
         17 . A method for treating a disease, disorder or condition in a subject, the method comprising administering the nanoparticle of  claim 1  to the subject. 
     
     
         18 . The method of  claim 17 , wherein the disease, disorder or condition is cancer. 
     
     
         19 . A method for treating a disease, disorder or condition in a subject, the method comprising administering the nanoparticle of  claim 14  to the subject. 
     
     
         20 . The method of  claim 19 , wherein the disease, disorder or condition is cancer. 
     
     
         21 . The nanoparticle of  claim 1 , further comprising a ligand for a second cellular receptor. 
     
     
         22 . The nanoparticle of  21  wherein the ligand for a second cellular receptor is a protein. 
     
     
         23 . The nanoparticle of  claim 22 , wherein the ligand for a second cellular receptor comprises transferrin. 
     
     
         24 . The nanoparticle of  claim 21 , wherein:
 (a) the first polymer comprises a mucic acid-containing polymer coupled to a nitrophenylboronic acid-containing polymer;   (b) the ligand for a first cellular receptor is Herceptin®;   (c) the ligand for a second cellular comprises transferrin; and   (d) the therapeutic agent is a camptothecin-based drug.   
     
     
         25 . A pharmaceutical composition comprising the nanoparticle of  claim 21  and a pharmaceutically acceptable vehicle, excipient or diluent. 
     
     
         26 . A pharmaceutical composition comprising the nanoparticle of  claim 24  and a pharmaceutically acceptable vehicle, excipient or diluent. 
     
     
         27 . A method for treating a disease, disorder or condition in a subject, the method comprising administering the nanoparticle of  claim 21  to the subject. 
     
     
         28 . The method of  claim 27 , wherein the disease, disorder or condition is cancer. 
     
     
         29 . A method for treating a disease, disorder or condition in a subject, the method comprising administering the nanoparticle of  claim 24  to the subject. 
     
     
         30 . The method of  claim 29 , wherein the disease, disorder or condition is cancer. 
     
     
         31 . A nanoparticle comprising:
 (a) a first polymer containing a polyol coupled to a second polymer containing a phenylboronic acid;   (b) a first therapeutic agent; and   (c) a second therapeutic agent.   
     
     
         32 . The nanoparticle of  claim 31  wherein, in the first polymer, the polyol is a mucic acid polymer (MAP). 
     
     
         33 . The nanoparticle of  claim 32 , wherein the mucic acid polymer contains repeating units comprising: 
       
         
           
           
               
               
           
         
       
       wherein:
 n is 1. 
 
     
     
         34 . The nanoparticle of  claim 33 , wherein the mucic acid polymer has the structural unit: 
       
         
           
           
               
               
           
         
       
       derived from the coupling of A and B; 
       wherein A is 
       
         
           
           
               
               
           
         
       
       B is 
       
         
           
           
               
               
           
         
       
       and 
       wherein:
 sugar is mucic acid, 
 spacer is —CH 2 —CH 2 —NH—, 
 L is a leaving group, and 
 p is from 20-200. 
 
     
     
         35 . The nanoparticle of  claim 31  wherein, in the second polymer, the phenylboronic acid is a nitrophenylboronic acid. 
     
     
         36 . The nanoparticle of  claim 35 , wherein the second polymer has the structure: 
       
         
           
           
               
               
           
         
       
       and isomers thereof wherein:
 (a) the PEG moiety is attached to the phenyl ring in an ortho or a para position relative to the boronic acid moiety, and/or 
 (b) the nitro group is attached to the phenyl ring in an ortho or a para position relative to the boronic acid moiety; and 
 
       wherein s is from 20-300, and 
       functional group 2 comprises the first therapeutic agent. 
     
     
         37 . The nanoparticle of  claim 31 , wherein the first therapeutic agent is a protein. 
     
     
         38 . The nanoparticle of  claim 37 , wherein the protein is an antibody. 
     
     
         39 . The nanoparticle of  claim 38 , wherein the antibody is Herceptin®. 
     
     
         40 . The nanoparticle of  claim 31 , wherein the second therapeutic agent is a small molecule chemotherapeutic. 
     
     
         41 . The nanoparticle of  claim 40 , wherein the small molecule chemotherapeutic is selected from the group consisting of camptothecin, a camptothecin-based drug, an epothilone and a taxane. 
     
     
         42 . The nanoparticle of  claim 41 , wherein the small molecule chemotherapeutic is a camptothecin-based drug. 
     
     
         43 . The nanoparticle of  claim 40 , wherein the small molecule chemotherapeutic is attached to the first polymer through a biodegradable ester bond. 
     
     
         44 . The nanoparticle of  claim 31 , wherein:
 (a) the first polymer comprises a mucic acid-containing polymer coupled to a nitrophenylboronic acid-containing polymer;   (b) the first therapeutic agent is Herceptin®; and   (c) the second therapeutic agent is a camptothecin-based drug.   
     
     
         45 . A pharmaceutical composition comprising the nanoparticle of  claim 31  and a pharmaceutically acceptable vehicle, excipient or diluent. 
     
     
         46 . A pharmaceutical composition comprising the nanoparticle of  claim 44  and a pharmaceutically acceptable vehicle, excipient or diluent. 
     
     
         47 . A method for treating a disease, disorder or condition in a subject, the method comprising administering the nanoparticle of  claim 31  to the subject. 
     
     
         48 . The method of  claim 47 , wherein the disease, disorder or condition is cancer. 
     
     
         49 . A method for treating a disease, disorder or condition in a subject, the method comprising administering the nanoparticle of  claim 44  to the subject. 
     
     
         50 . The method of  claim 49 , wherein the disease, disorder or condition is cancer. 
     
     
         51 . The nanoparticle of  claim 31 , further comprising a ligand for a cellular receptor. 
     
     
         52 . The nanoparticle of  51 , wherein the ligand for a cellular receptor is a protein. 
     
     
         53 . The nanoparticle of  claim 52 , wherein the ligand for a cellular receptor comprises transferrin. 
     
     
         54 . The nanoparticle of  claim 51 , wherein:
 (a) the first polymer comprises a mucic acid-containing polymer coupled to a nitrophenylboronic acid-containing polymer;   (b) the first therapeutic agent is Herceptin®;   (c) the second therapeutic agent is a camptothecin-based drug; and   (d) the ligand for a cellular comprises transferrin.   
     
     
         55 . A pharmaceutical composition comprising the nanoparticle of  claim 51  and a pharmaceutically acceptable vehicle, excipient or diluent. 
     
     
         56 . A pharmaceutical composition comprising the nanoparticle of  claim 54  and a pharmaceutically acceptable vehicle, excipient or diluent. 
     
     
         57 . A method for treating a disease, disorder or condition in a subject, the method comprising administering the nanoparticle of  claim 51  to the subject. 
     
     
         58 . The method of  claim 57 , wherein the disease, disorder or condition is cancer. 
     
     
         59 . A method for treating a disease, disorder or condition in a subject, the method comprising administering the nanoparticle of  claim 54  to the subject. 
     
     
         60 . The method of  claim 59 , wherein the disease, disorder or condition is cancer.