SURFACE FUNCTIONALIZED, HOST-GUEST POLYMER NANO-ASSEMBLIES AND METHODS THEREOF
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)