A polymeric cascade prodrug comprising: - an amine containing biologically active moiety; - a masking group having at least one nucleophile and being distinct from the carrier; wherein the prodrug has the following structure: wherein T is D; D is a residue of an amine containing biologically active moiety, which is connected to the rest of the molecule through an amine group; X is a spacer moiety, such as R 5 -Y 6; Y 1, Y 2 are independently selected from the group consisting of O and S; Y 3, Y 5 are independently selected from the group consisting of O and S; Y 4 is O, NR6 or -C -; Y 6 is O, S, NR6, succinimide, maleimide, an unsaturated carbon-carbon bond, any heteroatom containing a free electron pair, or is absent; R2 and R3 are selected independently from the group consisting of hydrogen; substituted or non-substituted linear, branched or cyclical alkyl or heteroalkyl; aryls; substituted aryls; substituted or non-substituted heteroaryls; cyano; nitro; halogen; carboxy; carboxyalkyl; alkylcarbonyl and carboxamidoalkyl; each R4 is selected independently from the group consisting of hydrogen; substituted or non-substituted linear, branched or cyclical alkyl or heteroalkyl; aryl; substituted aryl; substituted or non-substituted heteroaryl; substituted or non-substituted linear, branched, or cyclical alkoxy; substituted or non-substituted linear, branched, or cyclical heteroalkyloxy; aryloxy; heteroaryloxy; cyano; and halogen; R5 is selected from the group consisting of substituted or non-substituted linear, branched or cyclical alkyl or heteroalkyl; aryls; substituted aryls; and substituted or non-substituted heteroaryls; R7 and R8 are independently selected from the group consisting of hydrogen; substituted or non-substituted linear, branched or cyclical alkyl or heteroalkyl; aryls; substituted aryls; substituted or non-substituted heteroaryls; carboxyalkyl; alkylcarbonyl; carboxamidoalkyl; cyano; and halogen; R6 is selected from the group consisting of hydrogen; substituted or non-substituted linear, branched or cyclical alkyl or heteroalkyl; aryls; substituted aryls; and substituted or non-substituted heteroaryls; R 1 is a polymer; W is selected from the group consisting of substituted or non-substituted linear, branched or cyclical alkyls; aryls; substituted aryls; substituted or non-substituted linear, branched or cyclical heteroalkyl; and substituted or nonsubstituted heteroaryls; Nu is a nucleophile selected from the group consisting of primary, secondary or tertiary amino groups; thiol; carboxylic acid; hydroxylamine and hydrazine; n is zero or a positive integer; and Ar is a multi-substituted aromatic hydrocarbon or a multi-substituted aromatic heterocycle selected from the group consisting of: and wherein each V is independently selected from the group consisting of O, S, and N. - an amine containing biologically active moiety; - a masking group having at least one nucleophile and being distinct from the carrier; T is D; D is a residue of an amine containing biologically active moiety, which is connected to the rest of the molecule through an amine group; X is a spacer moiety, such as R 5 -Y 6; Y 1, Y 2 are independently selected from the group consisting of O and S; Y 3, Y 5 are independently selected from the group consisting of O and S; Y 4 is O, NR6 or -C -; Y 6 is O, S, NR6, succinimide, maleimide, an unsaturated carbon-carbon bond, any heteroatom containing a free electron pair, or is absent; R2 and R3 are selected independently from the group consisting of hydrogen; substituted or non-substituted linear, branched or cyclical alkyl or heteroalkyl; aryls; substituted aryls; substituted or non-substituted heteroaryls; cyano; nitro; halogen; carboxy; carboxyalkyl; alkylcarbonyl and carboxamidoalkyl; each R4 is selected independently from the group consisting of hydrogen; substituted or non-substituted linear, branched or cyclical alkyl or heteroalkyl; aryl; substituted aryl; substituted or non-substituted heteroaryl; substituted or non-substituted linear, branched, or cyclical alkoxy; substituted or non-substituted linear, branched, or cyclical heteroalkyloxy; aryloxy; heteroaryloxy; cyano; and halogen; R5 is selected from the group consisting of substituted or non-substituted linear, branched or cyclical alkyl or heteroalkyl; aryls; substituted aryls; and substituted or non-substituted heteroaryls; R7 and R8 are independently selected from the group consisting of hydrogen; substituted or non-substituted linear, branched or cyclical alkyl or heteroalkyl; aryls; substituted aryls; substituted or non-substituted heteroaryls; carboxyalkyl; alkylcarbonyl; carboxamidoalkyl; cyano; and halogen; R6 is selected from the group consisting of hydrogen; substituted or non-substituted linear, branched or cyclical alkyl or heteroalkyl; aryls; substituted aryls; and substituted or non-substituted heteroaryls; R 1 is a polymer; W is selected from the group consisting of substituted or non-substituted linear, branched or cyclical alkyls; aryls; substituted aryls; substituted or non-substituted linear, branched or cyclical heteroalkyl; and substituted or nonsubstituted heteroaryls; Nu is a nucleophile selected from the group consisting of primary, secondary or tertiary amino groups; thiol; carboxylic acid; hydroxylamine and hydrazine; n is zero or a positive integer; and Ar is a multi-substituted aromatic hydrocarbon or a multi-substituted aromatic heterocycle selected from the group consisting of: and wherein each V is independently selected from the group consisting of O, S, and N.