Floxuridine Homomeric Oligonucleotides "Hitchhike" with Albumin In Situ for Cancer Chemotherapy.

ABSTRACT: Automated attachment of chemotherapeutic drugs to oligonucleotides through phosphoramidite chemistry and DNA synthesis has emerged as a powerful technology in constructing structure-defined and payload-tunable oligonucleotide-drug conjugates. In practice, however, in vivo delivery of these oligonucleotides remains a challenge. Inspired by the systemic transport of hydrophobic payloads by serum albumin in nature, we report the development of a lipid-conjugated floxuridine homomeric oligonucleotide (LFU20) that "hitchhikes" with endogenous serum albumin for cancer chemotherapy. Upon intravenous injection, LFU20 immediately inserts into the hydrophobic cave of albumin to form an LFU20/albumin complex, which accumulates in the tumor by the enhanced permeability and retention (EPR) effect and i

SUBMITTER: Jin C 

PROVIDER: S-EPMC6472956 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature