Oligonucleotide-functionalized hydrophobic polymer nanoparticles

A method for conjugating an oligonucleotide to a hydrophobic polymer nanoparticle, said method comprising:

• (i) reacting a hydrophobic polymer bearing at least a carboxyl group with a compound of formula (II′),
• wherein
• A represents a spacer chosen from:
• —(CH2)m—, —(CH2)pNH—CO(CH2)q—, —(CH2)pCO—NH(CH2)q—, —(CH2)pO(CH2)q—, —(CH2)pNH(CH2)qO—, —(CH2)mCO—, —CO(CH2)m—, each of m, p and q represent independently from each other an integer chosen from 0 to 8, preferably an integer chosen from 0 to 5, more preferably an integer chosen from 0 to 3,
• D represents a group chosen from:
• wherein R′ represents a hydrogen, a halogen, a (C1-C8)alkyl,
• a cyclo(C3-C7)alkyl eventually monosubstituted, a monocyclic non-aromatic heterocyclic group eventually monosubstituted, or a monocyclic aromatic group eventually monosubstituted,
• E represents Y—NRa, where Ra is H or an (C1-C8)alkyl,
• X, Y, Z identical or different and each represent a spacer chosen from —(CH2)r—, —(CH2—CH2—O)r—, —(CH2—CH2—NH)r—, —(CH2)sNH—CO(CH2)t—, —(CH2)sCO—NH(CH2)t—, r, s and t represent independently from each other an integer chosen from 0 to 8, preferably an integer chosen from 0 to 5, more preferably an integer chosen from 0 to 3;
• R1 represents:
• —COOH, eventually protected by a carboxyl protecting group, such tert butyl group,
• —PO(OH)2, —PO(ORb)OH, —O—PO(OH)2, —O—PO(ORb)OH, where Rb is methyl or ethyl,
• S(═O)2—OH, —OS(═O)2OH
• n represents an integer chosen from 1 to 10, in particular from 1 to 3
• when D represents
• E can be absent;
• to obtain a modified polymer, said chains bearing at least one motif of formula (I′),
• wherein A, D, X, Y, Z, R1 and n are as defined above,
• (ii) precipitating the modified polymer obtained in step (i) from an organic solvent into aqueous solution to produce the nanoparticles;
• (iii) carrying out a cycloaddition between the nanoparticles obtained in the previous step with:
• a non-specific oligonucleotide bearing a functional group capable of reacting with the azide group of the motif (I) by a cycloaddition, and/or
• a target-specific oligonucleotide bearing a functional group capable of reacting with the azide group of the motif (I) by a cycloaddition.