Floxuridine Homomeric Oligonucleotides “Hitchhike” with Albumin In Situ for Cancer Chemotherapy |
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| Authors: | Cheng Jin Hui Zhang Jianmei Zou Yan Liu Lin Zhang Fengjie Li Prof Ruowen Wang Wenjing Xuan Prof Mao Ye Prof Weihong Tan |
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| Affiliation: | 1. Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Life Sciences, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan, China;2. Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, and College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, China;3. Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Health Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, FL, USA |
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| 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 internalizes into the lysosomes of cancer cells. After degradation, cytotoxic floxuridine monophosphate is released to inhibit cell proliferation. |
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| Keywords: | albumin cancer chemotherapy drug delivery floxuridine lipid-conjugated oligonucleotides |
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