Despite functional evidence for acid sensitive bond cleavage of dendritic polyglycerol drug-conjugates in cellular compartments, the mechanistic details pertaining to such process (e.g. kinetics and sites of cleavage) remain unexplored. To address these questions directly, we are working on the synthesis of a novel FRET-based polymer conjugates that changes its fluorescence upon drug release. Fluorescence analysis of the first conjugates revealed that pH dependent bond cleavage can be measured by fluorescence spectrophotometry at endosomal and lysosomal pHs. A new approach would be the introduction of targeting moieties (e.g. peptides, antibodies) to improve selectivity to specified tissue or sites.