Nanogels

1. A PA polymer according to Formula (1) or (2):

wherein: A is independently selected from a direct carbon-carbon single bond, O, N(R 1 ) and S;

R 1 is independently selected from H and CH 3 ;

R 2 is independently selected from the group consisting of:

(a) C 1 -C 40 alkylene, wherein the alkylene group may be linear or branched and is optionally substituted and/or is optionally unsaturated and/or is optionally interrupted by one or more heteroatoms, wherein the heteroatoms are independently selected from O, N and S, and/or wherein the alkylene group is interrupted by one or more —S—S— groups;

(b) C 3 -C 40 cycloalkylene, wherein the cycloalkylene group is optionally substituted and/or is optionally unsaturated and/or optionally comprises one or more heteroatoms in the ring, wherein the heteroatoms are independently selected from O, N and S, and/or wherein the cycloalkylene group is interrupted by one or more —S—S— groups outside the ring;

(c) C 6 -C 40 arylene, wherein the arylene group is optionally substituted;

(d) C 6 -C 40 heteroarylene, wherein the heteroarylene group comprises one, two or three heteroatoms independently selected from O, N and S and/or wherein the heteroarylene group is optionally substituted;

(e) C 7 -C 40 alkylarylene wherein the alkylarylene group is optionally substituted and/or wherein an alkyl part of the alkylarylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one or more heteroatoms, wherein the heteroatoms are independently selected from O, N and S, and/or wherein an alkyl part of the alkylarylene group is interrupted by one or more —S—S— groups;

(f) C 7 -C 40 alkylheteroarylene, wherein the alkylheteroarylene group comprises one, two or three heteroatoms independently selected from O, N and S and/or wherein the alkylheteroarylene group is optionally substituted, and/or wherein an alkyl part of the alkylheteroarylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one or more heteroatoms, wherein the heteroatoms are independently selected from O, N and S, and/or wherein an alkyl part of the alkylheteroarylene group is interrupted by one or more —S—S— groups; and

(g) a group wherein two C 7 -C 40 (hetero)arylene groups and/or C 7 -C 40 alkyl(hetero)arylene groups are connected to each other by a —S—S— group, wherein the alkyl part of the alkyl(hetero)arylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one or more heteroatoms, wherein the heteroatoms are independently selected from O, N and S;

R 3 is independently selected from the group consisting of:

(a) H;

(b) C 1 -C 10 alkyl, wherein the alkyl group may be linear or branched and is optionally substituted and/or is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S;

(C) C 3 -C 12 cycloalkyl, wherein the cycloalkyl group is optionally substituted and/or is optionally unsaturated and/or optionally comprises one, two or three heteroatoms in the ring, wherein the heteroatoms are independently selected from O, N and S;

(d) C 6 -C 12 aryl, wherein the aryl group is optionally substituted;

(e) C 6 -C 12 heteroaryl, wherein the heteroaryl group comprises one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S, and wherein the heteroaryl group is optionally substituted;

(f) C 7 -C 14 alkylaryl wherein the alkylaryl group is optionally substituted and/or wherein an alkyl part of the alkylarylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S; and

(g) C 7 -C 14 alkylheteroaryl, wherein the alkylheteroaryl group comprises one, two or three heteroatoms independently selected from O, N and S and/or wherein the alkylheteroarylene group is optionally substituted, and/or wherein an alkyl part of the alkylheteroarylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S;

R 4 is independently selected from the group consisting of:

(a) H;

(b) C 1 -C 10 alkyl, wherein the alkyl group may be linear or branched;

(C) C 3 -C 12 cycloalkyl;

(d) C 6 -C 14 aryl;

(e) C 6 -C 14 heteroaryl, wherein the alkylheteroaryl group comprises one, two or three heteroatoms independently selected from O, N and S;

(f) C 7 -C 14 alkylaryl; and

(g) C 7 -C 14 alkylheteroaryl, wherein the alkylheteroaryl group comprises one, two or three heteroatoms independently selected from O, N and S;

R 5 is independently selected from the group consisting of:

(a) C 1 -C 12 alkylene, wherein the alkylene group may be linear or branched and is optionally substituted and/or is optionally unsaturated and/or is optionally interrupted by one or more heteroatoms, wherein the heteroatoms are independently selected from O, N and S:

(b) C 3 -C 12 cycloalkylene, wherein the cycloalkylene group is optionally substituted and/or is optionally unsaturated and/or optionally comprises one or more heteroatoms in the ring, wherein the heteroatoms are independently selected from O, N and S;

(c) C 6 -C 12 arylene, wherein the arylene group is optionally substituted;

(d) C 6 -C 12 heteroarylene, wherein the heteroarylene group comprises one, two or three heteroatoms independently selected from O, N and S and/or wherein the heteroarylene group is optionally substituted;

(e) C 7 -C 12 alkylarylene wherein the alkylarylene group is optionally substituted and/or wherein an alkyl part of the alkylarylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one or more heteroatoms, wherein the heteroatoms are independently selected from O, N and S; and

(f) C 7 -C 12 alkylheteroarylene, wherein the alkylheteroarylene group comprises one, two or three heteroatoms independently selected from O, N and S and/or wherein the alkylheteroarylene group is optionally substituted, and/or wherein an alkyl part of the alkylheteroarylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one or more heteroatoms, wherein the heteroatoms are independently selected from O, N and S;

POL represents a polymeric core having a weight average molecular weight M w of about 300 to about 25000;

a=2-64; and

b=1-50.

2. The polymer according to claim 1 , wherein the weight average molecular weight M w of the polymer core POL is about 300 to about 5000.

3. The polymer according to claim 1 , wherein the polymeric core POL is based on or is selected from a branched, hyperbranched, multi-arm, dentritic or star-type (co)polymer.

4. The polymer according to claim 3 , wherein the (co)polymer has 2-64 terminal amino groups.

5. The polymer according to claim 4 , wherein the amino groups are primary amino groups.

6. The polymer according to claim 1 , wherein the polymer core POL is based on or is selected from the group consisting of PEI, PAMAM, PPI, PEAN and PEAC.

7. The polymer according to claim 6 , wherein the PEI is represented by the general Formula (5a) or (5b):

wherein n is such that the PEI has a weight average molecular weight M w of about 600 to about 3000.

8. The polymer according to claim 6 , wherein the polymer core POL is based on or is selected from the group consisting of the polymers represented by the general Formulas (6)-(9):

N(R 8 ) 3-n [(CR 9 2 ) m —N(R 10 R 11 )] n   (6)

[(R 10 R 11 )N—(CR 9 2 ) m ] 2 N—P—N[(CR 9 2 ) m —N(R 10 R 11 )] 2   (7)

N(R 8 ) 3-n [(CR 9 2 ) m —C(O)N(R 9 )—(CR 9 2 ) m —N(R 12 R 13 )] n   (8)

[(R 12 R 13 )N—(CR 9 2 ) m —N(R 9 )C(O)—(CR 9 2 ) m ] 2 N—P—N[(CR 9 2 )—C(O)NH—(CR 9 2 ) m —N(R 12 R 13 )] 2   (9)

wherein:

R 8 is a hydrogen atom, a linear or branched C 1 -C 20 alkyl group or a —[(CR 14 2 ) q —X] o —R 15 group, wherein X is O or N(R 8 );

m is 2, 3 or 4;

n is 2 or 3;

o is 1-10;

q is 2, 3 or 4;

P is —(CR 9 2 ) m —, a C 6 -C 12 arylene group, a C 6 -C 12 cycloalkylene group or a [(CR 14 2 ) q —X] p —C(R 14 ) 2 ]— group, wherein X is O or N(R 8 ) and p is 1-10;

R 9 is a hydrogen atom or a linear or branched C 1 -C 6 alkyl group;

R 10 and R 11 are independently a hydrogen atom, a linear or branched C 1 -C 6 alkyl group or a group of the formula —(CR 14 2 ) q NR 16 R 17 , provided that R 10 and R 11 are not both a linear or branched C 1 -C 6 alkyl group;

R 16 and R 17 are independently a hydrogen atom, a linear or branched C 1 -C 6 alkyl group or a group of the formula —(CR 14 2 ) q NR 18 R 19 , provided that R 16 and R 17 are not both a linear or branched C 1 -C 6 alkyl group;

R 18 and R 19 are independently a hydrogen atom, a linear or branched C 1 -C 6 alkyl group or a group of the formula —(CR 14 2 ) q NR 20 R 21 , provided that R 18 and R 19 are not both a linear or branched C 1 -C 6 alkyl group;

R 20 and R 21 are independently a hydrogen atom or a linear or branched C 1 -C 6 alkyl group, provided that R 20 and R 21 are not both a linear or branched C 1 -C 6 alkyl group;

R 22 is a hydrogen atom or a methyl group, provided that at least one R 22 is a hydrogen atom;

R 15 is a hydrogen or linear or branched C 1 -C 20 alkyl group;

R 12 and R 13 are independently a hydrogen atom, a linear or branched C 1 -C 6 alkyl group or a group of the formula —(CR 9 2 ) m —C(O)NH—(CR 9 2 ) m —N(R 23 R 24 ), provided that R 12 and R 13 are not both a linear or branched C 1 -C 6 alkyl group;

R 23 and R 24 are independently a hydrogen atom, a linear or branched C 1 -C 6 alkyl group or a group of the formula —(CR 9 2 ) m —C(O)NH—(CR 9 2 ) m —N(R 25 R 26 ), provided that R 23 and R 24 are not both a linear or branched C 1 -C 6 alkyl group;

R 25 and R 26 are independently a hydrogen atom, a linear or branched C 1 -C 6 alkyl group or a group of the formula —(CR 9 2 ) m —C(O)NH—(CR 9 2 ) m —N(R 27 R 28 ), provided that R 25 and R 26 are not both a linear or branched C 1 -C 6 alkyl group; and

R 27 and R 28 are independently a hydrogen atom or a linear or branched C 1 -C 6 alkyl group, provided that R 27 and R 28 are not both a linear or branched C 1 -C 6 alkyl group.

9. A process for the preparation of a PA polymer of claim 1 according to general Formulas (1) or (2), said process comprising the steps of:

(1) reacting a monomer (I) according to general formula (12):

wherein R 1 , A, and R 2 are as defined in claim 1 , with a monomer (II) according to general Formula (13) or a monomer (III) according to general Formula (14):

(H 2 N)—R 3   (13)

HR 3 N—R 5 —NR 3 H  (14)

wherein R 3 and R 5 are as defined in claim 1 , in a molar ratio of monomer (I):monomer (II) of from about 1.5:1 to about 10:1 to form a macromer according to general Formula (15) or (16):

wherein b is as defined in claim 1 ; and

(2) reacting the macromer according to general Formula (15) or (16) with a polymer according to Formula (17):

[(R 4 2 )N] a -POL  (17)

wherein a and R 4 are as defined in claim 1 and wherein at least one R 4 is H.

10. A PA polymer according to general Formulas (1) or (2) obtainable by the process according to claim 9 .

11. A nanogel comprising the PA polymer according to claim 1 .

12. The nanogel according to claim 11 , wherein the nanogel comprises a biologically active component.

13. The nanogel according to claim 12 , wherein the biologically active component is selected from the group consisting of RNA (in particular siRNA and miRNA) or derivatives or fragments hereof, DNA or derivatives or fragments hereof, (oligo)peptides and derivatives thereof, and proteins and derivatives thereof.

14. A process for preparing a nanogel comprising cross-linking a PA polymer according to general Formulas (1) or (2) according to claim 1 .

15. The process according to claim 14 , wherein the cross-linking is conducted by UV radiation.

16. A nanoparticle having the general Formula (3) or (4):

wherein R 1 , R 2 , R 3 , R 4 , R 5 , A, POL, a and b are as defined in claim 1 ; and

R 6 is selected from the group consisting of:

(a) C 1 -C 40 alkylene, wherein the alkylene group may be linear or branched and is optionally substituted and/or is optionally unsaturated and/or is optionally interrupted by one or more heteroatoms, wherein the heteroatoms are independently selected from O, N and S, and/or wherein the alkylene group is interrupted by one or more —S—S— groups; or

(b) C 3 -C 40 cycloalkylene, wherein the cycloalkylene group is optionally substituted and/or is optionally unsaturated and/or optionally comprises one or more heteroatoms in the ring, wherein the heteroatoms are independently selected from O, N and S, and/or wherein the cycloalkylene group is interrupted by one or more —S—S— groups outside the ring; and

FG is a Functional Group which is selected from the group consisting of —OH, —OR 7 , —NH 2 ; —NH(R 7 ), —N(R 7 ) 2 , —C(O)OR 7 , —C(O)R 7 , —C(O)NHR 7 , and —C(O)NR 7 2 , wherein R 7 is independently selected from the group consisting of:

(a″) H;

(b″) C 1 -C 10 alkyl, wherein the alkyl group may be linear or branched and is optionally substituted and/or is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S;

(c″) C 3 -C 12 cycloalkyl, wherein the cycloalkyl group is optionally substituted and/or is optionally unsaturated and/or optionally comprises one, two or three heteroatoms in the ring, wherein the heteroatoms are independently selected from O, N and S;

(d″) C 6 -C 12 aryl, wherein the aryl group is optionally substituted;

(e″) C 6 -C 12 heteroaryl, wherein the heteroaryl group comprises one, two or three heteroatoms independently selected from O, N and S and/or wherein the heteroaryl group is optionally substituted;

(f″) C 7 -C 14 alkylaryl wherein the alkylaryl group is optionally substituted and/or wherein an alkyl part of the alkylarylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S; and

(g″) C 7 -C 14 alkylheteroaryl, wherein the alkylheteroaryl group comprises one, two or three heteroatoms independently selected from O, N and S and/or wherein the alkylheteroarylene group is optionally substituted, and/or wherein an alkyl part of the alkylheteroarylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S.

17. A process for preparing a nanoparticle comprising reacting a PA polymer according to general Formulas (1) or (2) according to claim 1 with a reagent according to formulas (26a) or (26b):

FG-R 6 —NHR  (26a)

FG—R 6 —SH  (26b)

wherein R 6 is selected from the group consisting of:

(a) C 1 -C 40 alkylene, wherein the alkylene group may be linear or branched and is optionally substituted and/or is optionally unsaturated and/or is optionally interrupted by one or more heteroatoms, wherein the heteroatoms are independently selected from O, N and S, and/or wherein the alkylene group is interrupted by one or more —S—S— groups; or

(b) C 3 -C 40 cycloalkylene wherein the cycloalkylene group is optionally substituted and/or is optionally unsaturated and/or optionally comprises one or more heteroatoms in the ring, wherein the heteroatoms are independently selected from O, N and S, and/or wherein the cycloalkylene group is interrupted by one or more —S—S— groups outside the ring;

FG is H or a Functional Group which is selected from the group consisting of —OH, —OR 7 , —NH 2 ; —NH(R 7 ), —NH(R 7 )2, —C(O)OR 7 , —C(O)R 7 , —C(O)NHR 7 , and —C(O)NR 7 2 , wherein R 7 is independently selected from the group consisting of:

(a″) H;

(b″) C 1 -C 10 alkyl, wherein the alkyl group may be linear or branched and is optionally substituted and/or is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S;

(c″) C 3 -C 12 cycloalkyl, wherein the cycloalkyl group is optionally substituted and/or is optionally unsaturated and/or optionally comprises one, two or three heteroatoms in the ring, wherein the heteroatoms are independently selected from O, N and S;

(d″) C 6 -C 12 aryl, wherein the aryl group is optionally substituted;

(e″) C 6 -C 12 heteroaryl, wherein the heteroaryl group comprises one, two or three heteroatoms independently selected from O, N and S and/or wherein the heteroaryl group is optionally substituted;

(f″) C 7 -C 14 alkylaryl wherein the alkylaryl group is optionally substituted and/or wherein an alkyl part of the alkylarylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S; and

(g″) C 7 -C 14 alkylheteroaryl, wherein the alkylheteroaryl group comprises one, two or three heteroatoms independently selected from O, N and S and/or wherein the alkylheteroarylene group is optionally substituted, and/or wherein an alkyl part of the alkylheteroarylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S; and

R 30 is independently selected from the group consisting of:

(a) H;

(b) C 1 -C 10 alkyl, wherein the alkyl group may be linear or branched and is optionally substituted and/or is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S;

(c) C 3 -C 12 cycloalkyl, wherein the cycloalkyl group is optionally substituted and/or is optionally unsaturated and/or optionally comprises one, two or three heteroatoms in the ring, wherein the heteroatoms are independently selected from O, N and S;

(d) C 6 -C 12 aryl, wherein the aryl group is optionally substituted;

(e) C 6 -C 12 heteroaryl, wherein the heteroaryl group comprises one, two or three heteroatoms independently selected from O, N and S and/or wherein the heteroaryl group is optionally substituted;

(f) C 7 -C 14 alkylaryl wherein the alkylaryl group is optionally substituted and/or wherein an alkyl part of the alkylarylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S; and

(g) C 7 -C 14 alkylheteroaryl, wherein the alkylheteroaryl group comprises one, two or three heteroatoms independently selected from O, N and S and/or wherein the alkylheteroarylene group is optionally substituted, and/or wherein an alkyl part of the alkylheteroarylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S.

18. A surface modified nanogel obtained by a process comprising the steps of:

(1) cross-linking a PA polymer according to general Formulas (1) or (2) according to claim 1 ;

(2) optionally loading the nanogel with a biologically active component; and

(3) reacting the nanogel with a reactant R-CFG or R′—SH,

wherein:

R and R′ are selected from the group consisting of 2-thioethyl, 2-hydroxyethyl, PEG (polyethylene oxide) residues and PPO (polypropylene oxide) residues, wherein the PEG residues and the PPO residues have a number average molecular weight M n of about 500 to about 10000; CFG is a group capable of forming a covalent bond with a group FG, wherein FG is H or a Functional Group which is selected from the croup consisting of —OH, —OR 7 , —NH 2 ; —NH(R 7 ), —N(R 7 ) 2 , —C(O)OR 7 , —C(O)R 7 , —C(O)NHR 7 , and —C(O)NR 7 2 , wherein R 7 is independently selected from the group consisting of:

(a″) H;

(b″) C 1 -C 10 alkyl, wherein the alkyl group may be linear or branched and is optionally substituted and/or is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S;

(c″) C 3 -C 12 cycloalkyl, wherein the cycloalkyl group is optionally substituted and/or is optionally unsaturated and/or optionally comprises one, two or three heteroatoms in the ring, wherein the heteroatoms are independently selected from O, N and S;

(d″) C 6 -C 12 aryl, wherein the aryl group is optionally substituted;

(e″) C 6 -C 12 heteroaryl, wherein the heteroaryl group comprises one, two or three heteroatoms independently selected from O, N and S and/or wherein the heteroaryl group is optionally substituted;

(f″) C 7 -C 14 alkylaryl wherein the alkylaryl group is optionally substituted and/or wherein an alkyl part of the alkylarylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S; and

(g″) C 7 -C 14 alkylheteroaryl, wherein the alkylheteroaryl group comprises one, two or three heteroatoms independently selected from O, N and S and/or wherein the alkylheteroarylene group is optionally substituted, and/or wherein an alkyl part of the alkylheteroarylene group is linear or branched and is optionally unsaturated and/or is optionally interrupted by one, two or three heteroatoms, wherein the heteroatoms are independently selected from O, N and S; and

wherein the sequence of steps (1), (2) and (3) is: (1)-(2)-(3), (1)-(3)-(2), or (3)-(1)-(2).