Poly(beta-thioester) polymers and polymeric nanoparticles

A method of inducing the expression of CD86, CD80, and/or CD40 in a subject in need thereof, the method comprising administering to the subject a polymer of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein,
• R1 is
• Y1 is C1-3 alkyl, (C1-6 alkyl)-NHC(═O), C═O, 5 to 10-membered heteroaryl, or absent, wherein heteroaryl is optionally substituted, independently for each occurrence, one, two, or three times with C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, halogen, or 6 to 10-membered aryl;
• Y2 is C1-6 alkyl, 6 to 10-membered aryl, biphenyl, 5 to 10-membered heteroaryl, (CH2CH2O)pCH2CH2, C═N—(C1-6 alkyl)-N═C, O, S, or SO2, wherein the alkyl, aryl, biphenyl, and heteroaryl are optionally substituted, independently for each occurrence, one, two, or three times with C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, (C0-3 alkyl)-OH, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, halogen, or carboxylic acid;
• R2 is C1-6 alkyl, 6 to 10-membered aryl, O, or
• Z1 is C1-6 alkyl or 6 to 10-membered aryl;
• Z2 is O, O(C═O)O, or absent;
• Z3 is 6 to 10-membered aryl, 5 to 10-membered heteroaryl, or absent;
• Z4 is C1-6 alkyl, 5 to 15-membered cycloalkyl, 5 to 15-membered heterocyclyl, 6 to 14-membered aryl, 5 to 15-membered heteroaryl, or (C═O)O-(6 to 10-membered aryl)-O(C═O), each of which are optionally substituted, independently for each occurrence one, two, or three times with C1-3 alkyl, C1-3 haloalkyl, or halogen;
• n is 25-250;
• p is 1, 2, 3, or 4;
• and
• wherein R1, R2, Y1, Y2, Z1, Z2, Z3, and Z4 are each, independently, the same for every occurrence in the polymer.

A method of increasing the levels of interferon-γ in a subject in need thereof, the method comprising administering to the subject a polymer of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein,
• R1 is
• Y1 is C1-3 alkyl, (C1-6 alkyl)-NHC(═O), C═O, 5 to 10-membered heteroaryl, or absent, wherein heteroaryl is optionally substituted, independently for each occurrence, one, two, or three times with C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, halogen, or 6 to 10-membered aryl;
• Y2 is C1-6 alkyl, 6 to 10-membered aryl, biphenyl, 5 to 10-membered heteroaryl, (CH2CH2O)pCH2CH2, C═N—(C1-6 alkyl)-N═C, O, S, or SO2, wherein the alkyl, aryl, biphenyl, and heteroaryl are optionally substituted, independently for each occurrence, one, two, or three times with C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, (C0-3 alkyl)-OH, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, halogen, or carboxylic acid;
• R2 is C1-6 alkyl, 6 to 10-membered aryl, O, or
• Z1 is C1-6 alkyl or 6 to 10-membered aryl;
• Z2 is O, O(C═O)O, or absent;
• Z3 is 6 to 10-membered aryl, 5 to 10-membered heteroaryl, or absent;
• Z4 is C1-6 alkyl, 5 to 15-membered cycloalkyl, 5 to 15-membered heterocyclyl, 6 to 14-membered aryl, 5 to 15-membered heteroaryl, or (C═O)O-(6 to 10-membered aryl)-O(C═O), each of which are optionally substituted, independently for each occurrence, one, two, or three times with C1-3 alkyl, C1-3 haloalkyl, or halogen;
• n is 25-250;
• p is 1, 2, 3, or 4;
• and
• wherein R1, R2, Y1, Y2, Z1, Z2, Z3, and Z4 are each, independently, the same for every occurrence in the polymer.