Aptamer-Gemcitabine Conjugates with Enzymatically Cleavable Linker for Targeted Delivery and Intracellular Drug Release in Cancer Cells.

ABSTRACT: Gemcitabine is a chemotherapeutic used clinically to treat a variety of cancers. However, because it lacks tumor cell specificity, gemcitabine may cause off-target cytotoxicity and adversely impact patients. To impart cancer cell specificity to gemcitabine and improve its therapeutic efficacy, we synthesized a unique aptamer-drug conjugate that carries a high gemcitabine payload (three molecules) via a dendrimer structure and enzymatically cleavable linkers for controlled intracellular drug release. First, linker-gemcitabinedendrimer-linker-gemcitabine products were produced, which had significantly lower cytotoxicity than an equimolar amount of free drug. Biochemical analysis revealed that lysosomal cathepsin B protease rapidly cleaved the dendritic linkers and released the conjugated gem

SUBMITTER: Qi J 

PROVIDER: S-EPMC9147807 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature