主权项 |
1. A micelle having a polynucleotide encapsulated therein, comprising a diblock copolymer of formula I-b: wherein:
n is 50-2500;x1 is 0 to 250;x2 is 0 to 250;z1 is 0 to 250, provided that x1 and z1 are not simultaneously zero;z2 is 0 to 250, provided that z1 and z2 are not simultaneously zero; Rx is a natural or unnatural amino acid side-chain group that is hydrophobic; Rz is -L-R4 wherein:
L is a bivalent, straight or branched, C4-20 alkylene chain wherein at least one methylene unit of -L- is replaced by —C(O)NR— and 1-10 additional methylene units are independently replaced by —N(R)— or -Het-;Het is a bivalent 5-6 membered saturated, partially unsaturated, or aromatic ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
R4 is R or N(R)2;each R is hydrogen or C1-6 aliphatic, or two R on the same nitrogen are taken together with the nitrogen to form a 5-6 membered heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R1 is —Z(CH2CH2Y)p(CH2)tR3, wherein:
Z is a valence bond, a bivalent triazolyl moiety, —O—, —S—, —C≡C—, or —CH2—;each Y is independently —O— or —S—;p is 0-10;t is 0-10; and R3 is hydrogen, —N3, —CN, a mono-protected amine, a di-protected amine, a protected aldehyde, a protected hydroxyl, a protected carboxylic acid, a protected thiol, a 9-30 membered crown ether, or an optionally substituted group selected from aliphatic, a 5-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a detectable moiety or a targeting group; Q is a valence bond or a bivalent, saturated or unsaturated, straight or branched C1-12 alkylene chain, wherein 0-6 methylene units of Q are independently replaced by -Cy-, —O—, —NH—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —SO—, —SO2—, —NHSO2—, —SO2NH—, —NHC(O)—, —C(O)NH—, —OC(O)NH—, or —NHC(O)O—, wherein:
-Cy- is an optionally substituted 5-8 membered bivalent, saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an optionally substituted 8-10 membered bivalent saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R2 is selected from an optionally substituted aliphatic group or a fusogenic peptide.
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