Reversible immobilization and/or controlled release of nucleic acid containing nanoparticles by (biodegradable) polymer coatings

A nanoparticle comprising a complex of a nucleic acid and a polymeric carrier molecule according to generic formula (I):

• L-P1—S—[S—P2—S]n—S—P3-L (formula I)
• wherein,
• P1 and P3 are different or identical to each other and represent a linear or branched hydrophilic polymer chain, each P1 and P3 exhibiting at least one —SH-moiety, capable to form a disulfide linkage upon condensation with component P2, the linear or branched hydrophilic polymer chain selected independent from each other from polyethylene glycol (PEG), poly-N-(2-hydroxypropyl)methacrylamide, poly-2-(methacryloyloxy)ethyl phosphorylcholines, poly(hydroxyalkyl L-asparagine), poly(2-(methacryloyloxy)ethyl phosphorylcholine), hydroxyethylstarch and poly(hydroxyalkyl L-glutamine), wherein the hydrophilic polymer chain exhibits a molecular weight of about 1 kDa to about 100 kDa,
• P2 is a cationic or polycationic polypeptide, having a length of 3 to 100 amino acids, and comprising at least two cysteine residues;
• —S—S— is a (reversible) disulfide bond, wherein one of the sulfur positions of each of the disulfide bonds is provided by the at least two cysteine residues of P2;
• L is an optional ligand, which may be present or not, and may be selected independent from the other from RGD, Transferrin, Folate, a signal peptide or signal sequence, a localization signal or sequence, a nuclear localization signal or sequence (NLS), an antibody, a cell penetrating peptide, TAT, a ligand of a receptor, cytokines, hormones, growth factors, small molecules, carbohydrates, mannose, galactose, synthetic ligands, small molecule agonists, inhibitors or antagonists of receptors, and RGD peptidomimetic analogues;
• and
• n is an integer, selected from a range of about 1 to 50,
• wherein the nanoparticle is coated with a biodegradable polymer.

Method for preparing a coated nanoparticle comprising:

• a) providing a nanoparticle comprising a complex of a nucleic acid and a polymeric carrier molecule according to generic formula (I):
• L-P1—S—[S—P2—S]n—S—P3-L (formula I)
• wherein,
• P1 and P3 are different or identical to each other and represent a linear or branched hydrophilic polymer chain, each P1 and P3 exhibiting at least one —SH-moiety, capable to form a disulfide linkage upon condensation with component P2, the linear or branched hydrophilic polymer chain selected independent from each other from polyethylene glycol (PEG), poly-N-(2-hydroxypropyl)methacrylamide, poly-2-(methacryloyloxy)ethyl phosphorylcholines, poly(hydroxyalkyl L-asparagine), poly(2-(methacryloyloxy)ethyl phosphorylcholine), hydroxyethylstarch and poly(hydroxyalkyl L-glutamine), wherein the hydrophilic polymer chain exhibits a molecular weight of about 1 kDa to about 100 kDa,
• P2 is a cationic or polycationic polypeptide, having a length of 3 to 100 amino acids, and comprising at least two cysteine residues;
• —S—S— is a (reversible) disulfide bond, wherein one of the sulfur positions of each of the disulfide bonds in provided by the at least two cysteine residues of P2;
• L is an optional ligand, which may be present or not, and may be selected independent from the other from RGD, Transferrin, Folate, a signal peptide or signal sequence, a localization signal or sequence, a nuclear localization signal or sequence (NLS), an antibody, a cell penetrating peptide, TAT, a ligand of a receptor, cytokines, hormones, growth factors, small molecules, carbohydrates, mannose, galactose, synthetic ligands, small molecule agonists, inhibitors or antagonists of receptors, and RGD peptidomimetic analogues;
• and
• n is an integer, selected from a range of about 1 to 50;
• b) contacting the nanoparticle of a) with a biodegradable polymer in an organic solvent containing solution, and
• c) optionally, removing the organic solvent.