Delivery systems for controlled drug release

A compound having the structure of Formula (I):

• or a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof;
• wherein:
• Agent is selected from the group consisting of a cytostatic agent, a cytotoxic agent, a cytokine, an immunosuppressive agent, an antirheumatic, an antiphlogistic, an antibiotic, an analgesic, a virostatic agent, an anti-inflammatory agent, an antimicotic agent, a transcription factor inhibitor, a cell cycle modulator, an MDR modulator, a proteasome or protease inhibitor, an apoptosis modulator, an enzyme inhibitor, a signal transduction inhibitor, a protease inhibitor, an angiogenesis inhibitor, a hormone or hormone derivative, an antibody or a fragment thereof, a therapeutically or diagnostically active peptide, a radioactive substance, a light emitting substance, a light absorbing substance, and a derivative of any of the foregoing;
• Spacer is absent, or is selected from the group consisting of
• n is 0 or 1;
• X is selected from the group consisting of optionally substituted C1-C18 alkyl wherein optionally up to six carbon atoms in said C1-C18 alkyl are each independently replaced with —OCH2CH2—;
• optionally substituted C1-C18 alkyl-NH—C(O)—R5— wherein optionally up to six carbon atoms in said C1-C18 alkyl are each independently replaced with —OCH2CH2—, optionally substituted C1-C18 alkyl-C(O)—NH—R5— wherein optionally up to six carbon atoms in said C1-C18 alkyl are each independently replaced with —OCH2CH2—;
• optionally substituted aryl;
• optionally substituted heteroaryl;
• and optionally substituted cycloalkyl;
• R5 is selected from the group consisting of an optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted cycloalkyl;
• Y is absent or selected from the group consisting of optionally substituted C1-C6 alkyl, —NH—C(O)—, —C(O)—NH—, —C(O)—O—, and —O—C(O)—;
• R1 is absent or selected from the group consisting of optionally substituted C1-C18 alkyl wherein optionally up to six carbon atoms in said C1-C18 alkyl are each independently replaced with —OCH2CH2—;
• optionally substituted C1-C18 alkyl-NH—C(O)R5— wherein optionally up to six carbon atoms in said C1-C18 alkyl are each independently replaced with —OCH2CH2—, and optionally substituted C1-C18 alkyl-C(O)—NH—R5— wherein optionally up to six carbon atoms in said C1-C18 alkyl are each independently replaced with —OCH2CH2—,
• or R1 is a naturally or non-naturally occurring amino acid,
• or R1 has the following formula:
• wherein:
• is absent, or is selected from the group consisting of:
• R is:
• OPO3M1 wherein M1=Mg2, 2 Na+, 2K+, 2H+, 2NH4+;
• or
• SO3M2 wherein M2=Na+, K+, H+, NH4+;
• R2 is selected from the group consisting of —H, optionally substituted C1-C12 alkyl, optionally substituted aryl, and optionally substituted heteroaryl;
• Z1, Z2, Z3 and Z4 are each independently —H, an electron-withdrawing group, and/or a water-soluble group;
• PBG is a protein-binding group selected from the group consisting of an optionally substituted maleimide group, an optionally substituted haloacetamide group, an optionally substituted haloacetate group, an optionally substituted pyridylthio group, an optionally substituted isothiocyanate group, an optionally substituted vinylcarbonyl group, an optionally substituted aziridine group, an optionally substituted disulfide group, an optionally substituted acetylene group, an optionally substituted N-hydroxysuccinimide ester group, an antibody or fragment thereof, and a derivatized antibody of derivatized fragment thereof;
• wherein when Spacer is absent, Agent is linked to the nitrogen adjacent to Spacer by a double bond;
• and
• wherein at least one of Z1, Z2, Z3 and Z4 is an electron-withdrawing group.