Surface functionalized, host-guest polymer nano-assemblies and methods thereof

Abstract

The invention generally relates to polymer-based nano-structures. More particularly, the invention relates to novel, surface-functionalized, guest-host polymer nano-assemblies and nano-delivery vehicles useful in diverse fields including drug delivery, diagnostics and specialty materials. The nano-assemblies and nano-delivery vehicles of the invention are afforded via simplify and reliable approaches.

1 . A nano-assembly comprising:
 a host crosslinked polymer network having a functionalized surface with one or more functional groups; and   a guest molecular cargo non-covalently encapsulated in the host crosslinked polymer network,   
       wherein the host crosslinked polymer network is addressable by a biological or chemical intervention resulting in partial or complete decrosslinking of the host polymer network and release of the guest molecular cargo from the nano-assembly. 
     
     
         2 . The nano-assembly of  claim 1 , wherein the host crosslinked polymer network is a nanogel. 
     
     
         3 . (canceled) 
     
     
         4 . The nano-assembly of  claim 2 , wherein the host crosslinked polymer network is formed from a random copolymer comprising 
       
         
           
           
               
               
           
         
       
       wherein
 each of Z 1  and Z 2  is independently 
 
       
         
           
           
               
               
           
         
       
       wherein Z′ is selected from O, NH, NR (R═C 1 -C 6  alkyl group or R F );
 each of R 1  and R 2  is independently selected from a hydrogen, C 1 -C 12  alkyl group, or halogen; 
 each of R L1  and R L2  is independently a single bond or a spacer group; 
 R F  is —H or a functional group; 
 R x  is a crosslinking group capable of inter- or intra-molecular crosslinking; 
 R x′  is an inter- or intra-molecularly crosslinked group; and 
 i=a·n, j=x·n, and k=b·n−x·n, wherein each of a and b is a positive number with a+b =1, each of n and x is independently an integer from about 0.1% to about 100% of b. 
 
     
     
         5 . The nano-assembly of  claim 4 , wherein each of R 1  and R 2  is methyl. 
     
     
         6 . The nano-assembly of  claim 4 , wherein each of R il  and R L2  is selected from —(CH 2 ) m —, wherein m is an integer from about 1 to about 15, and —(CH 2 CH 2 —O) q —, wherein q is an integer from about 1 to about 50. 
     
     
         7 . The nano-assembly of  claim 4 , wherein R F  is selected from the group consisting of amines, carboxylates, hydroxyl, halides, acyl halides, esters, azides, nitriles, amides, epoxides, aldehydes, furans, alkenes and alkynes. 
     
     
         8 . The nano-assembly of  claim 7 , wherein R F  is an amine. 
     
     
         9 . The nano-assembly of  claim 7 , wherein R F  is an activated carboxylic ester. 
     
     
         10 . The nano-assembly of  claim 4 , wherein R x  comprises a reactive group selected from coumarin, alkenes, thiols, reactive disulfides, alkynes, furans, aldehydes, amines, activated esters, maleimides, and epoxides. 
     
     
         11 . (canceled) 
     
     
         12 . The nano-assembly of  claim 2 , wherein the host crosslinked polymer network is formed from a homopolymer comprising 
       
         
           
           
               
               
           
         
       
       wherein Z 3  is 
       
         
           
           
               
               
           
         
       
       wherein Z′ is selected from O, NH, NR (R═C 1 -C 6  alkyl group or R F );
 R 3  is selected from a hydrogen, C 1 -C 12  alkyl group, or halogen; 
 R L3  is CR 4 , N or a trivalent group, wherein R 4  is selected from a hydrogen, C 1 -C 12  alkyl group, or halogen; 
 R F  is —H or a functional group; 
 R x  is a crosslinking group capable of inter- or intra-molecular crosslinking or an inter- or intra-molecularly crosslinked group; and 
 r is an integer from about 10 to about 1000. 
 
     
     
         13 . The nano-assembly of  claim 12 , wherein R 3  is —H or -methyl. 
     
     
         14 . The nano-assembly of  claim 12 , wherein R L3  is CH. 
     
     
         15 . The nano-assembly of  claim 12 , wherein R F  is selected from the group consisting of amines, carboxylates, hydroxyl, halides, acyl halides, esters, azides, nitriles, amides, epoxides, aldehydes, furans, alkenes and alkynes. 
     
     
         16 . The nano-assembly of  claim 15 , wherein R F  comprises an amine group. 
     
     
         17 . The nano-assembly of  claim 15 , wherein R F  comprises a carboxylate group. 
     
     
         18 . The nano-assembly of  claim 12 , wherein R x  comprises a reactive group selected from coumarin, alkenes, thiols, reactive disulfides, alkynes, furans, aldehydes, and epoxides. 
     
     
         19 . The nano-assembly of  claim 12 , wherein the polymer network is formed from a homopolymer via a controlled crosslinking. 
     
     
         20 . The nano-assembly of  claim 1 , wherein the biological, physical or chemical intervention is a change in pH, redox reagent, redox potential, ionic strength, enzymatic activity, protein concentration, light, heat, or mechanical stress. 
     
     
         21 - 32 . (canceled) 
     
     
         33 . A method for controlled delivery of an agent to a target biological site, comprising:
 providing a nano-assembly of a host crosslinked polymer network non-covalently encapsulating therein a guest molecular cargo, wherein the host crosslinked polymer network is capable of partial or complete decrosslinking by a biological or chemical intervention resulting in release of the guest molecular cargo from the nano-assembly;   delivering the nano-assembly to the target biological site; and   causing a biological or chemical intervention resulting in a partial or complete decrosslinking resulting in release of the guest molecular cargo from the nano-assembly.   
     
     
         34 - 51 . (canceled) 
     
     
         52 . A nanoparticle comprising:
 a shell of a crosslinked polymer network having a surface functionalized with one or more functional groups; and   a core comprising a host polymer network and a guest agent non-covalently encapsulated therein,   
       wherein the core, the shell, or one or more intervening layers of the crosslinked polymer network are independently addressable by a biological or chemical intervention resulting in partial or complete disassembly of the shell, the one or more intervening layers, and/or the core thereby releasing of the guest agent. 
     
     
         53 - 92 . (canceled)