Non-symmetric DiPPro-nucleotides are described as nucleoside diphosphate (NDP) delivery systems. The basic concept of this approach is to attach two different bis(acyloxybenzyl)-moieties at the -phosphate moiety of a nucleoside diphosphate. Two types of DiPPro-prodrugs were studied: DiPPro-compounds bearing two alkanoylbenzyl residues in which the length of the alkanoyl ester group differed and second, DiPPro-compounds bearing an alkanoylbenzyl and a benzoylbenzyl group as bioreversible prodrug moieties. The introduction of two different groups resulted in different hydrolytic properties that allowed a controlled step-wise removal of the prodrug moieties. Prodrug moieties bearing short chain alkanoyl esters ensured a fast hydrolysis by chemical or enzymatic means. The ester group in the second prodrug group comprised of e.g. a long lipophilic aliphatic or aromatic residue. The high lipophilicity of the second mask enabled the prodrug to penetrate the cell membrane. Series of non-symmetric DiPPro-d4TDPs and -AZTDPs with different combinations of aliphatic and aromatic acyl moieties were synthesized. The aim of such DiPPro-compounds was to achieve a highly selective delivery of the NDP in various media, e.g. in cell extracts of CD4+ CEM T-lymphocytes. Studies in different media proved the selective formation of NDPs. In addition, these compounds were investigated against HIV-1 and HIV-2 and proved to be highly antivirally active, even in thymidine kinase-deficient CEM cell cultures. This indicates that the compounds although charged at the -phosphate group were able to be taken-up by the cells and released NDPs intracellularly.