Aptamer-Functionalized Drug Nanocarrier Improves Hepatocellular Carcinoma toward Normal by Targeting Neoplastic Hepatocytes

Molecular Therapy. Nucleic Acids
Samrat ChakrabortyRamkrishna Sen

Abstract

Site-specific delivery of chemotherapeutics specifically to neoplastic hepatocytes without affecting normal hepatocytes should be a focus for potential therapeutic management of hepatocellular carcinoma (HCC). The aptamer TLS 9a with phosphorothioate backbone modifications (L5) has not been explored so far for preferential delivery of therapeutics in neoplastic hepatocytes to induce apoptosis. Thus, the objective of the present investigation was to compare the therapeutic potential of L5-functionalized drug nanocarrier (PTX-NPL5) with those of the other experimental drug nanocarriers functionalized by previously reported HCC cell-targeting aptamers and non-aptamer ligands, such as galactosamine and apotransferrin. A myriad of well-defined investigations such as cell cycle analysis, TUNEL (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling) assay, and studies related to apoptosis, histopathology, and immunoblotting substantiated that PTX-NPL5 had the highest potency among the different ligand-attached experimental formulations in inducing selective apoptosis in neoplastic hepatocytes via a mitochondrial-dependent apoptotic pathway. PTX-NPL5 did not produce any notable toxic effects in healt...Continue Reading

Citations

Mar 27, 2020·International Journal of Molecular Sciences·Saikat DewanjeeVincenzo De Feo
Dec 4, 2020·International Journal of Molecular Sciences·Zhaoying Fu, Jim Xiang
Jan 5, 2021·Frontiers in Pharmacology·Biswajit MukherjeeVeranja Karunaratne
Apr 10, 2021·Biomaterials·Yachao ZhangShuangying Gui
Apr 30, 2021·Colloids and Surfaces. B, Biointerfaces·Soumya GangulyMita Chatterjee Debnath
Sep 8, 2021·Molecular Pharmaceutics·Yujing DuRongfu Wang

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Methods Mentioned

BETA
flow cytometry
confocal microscopy
DNA

Software Mentioned

DTS
BD FACSDiva
AxioVision
Biovia Discovery Studio

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