Cancer Cell Preferential Penetration and pH-Responsive Drug Delivery of Oligorutin
| Autor: | Min Xiao, Henan Zhang, Weiying Hong, Zhiyong Chen, Li Xu, Chang-Cheng Liu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Drug
Carcinoma Hepatocellular Polymers and Plastics media_common.quotation_subject Antineoplastic Agents Bioengineering Biomaterials Cell membrane Mice Drug Delivery Systems Cell Line Tumor Materials Chemistry medicine Animals Tissue Distribution Cytotoxicity Internalization media_common Chemistry Bortezomib Liver Neoplasms Cancer Hydrogen-Ion Concentration medicine.disease medicine.anatomical_structure Pharmaceutical Preparations Drug delivery Cancer cell Cancer research Nanoparticles medicine.drug |
| Zdroj: | Biomacromolecules. 22:3679-3691 |
| ISSN: | 1526-4602 1525-7797 |
| DOI: | 10.1021/acs.biomac.1c00268 |
| Popis: | We report herein a novel delivery system, derived from the facile enzymatic synthesis of oligorutin (OR), for cancer cell targeting and pH-responsive drug delivery. In this study, we demonstrate that OR could preferentially penetrate cancer cells via the lipid raft-mediated endocytosis pathway, and cell membrane cholesterol was critical to the internalization of OR. The accumulation of OR in the tumor region was further confirmed by an in vivo biodistribution study. Considering the tumor-targeting property of OR, a pH-responsive drug delivery system (OR-BTZ) was developed by covalent conjugation of the catechol groups on OR with antitumor drug bortezomib (BTZ) through a pH-sensitive borate ester bond. OR-BTZ exerted cytotoxicity as well as inhibition of the migration and invasion to hepatoma carcinoma cells and showed no apparent cytotoxicity with liver normal cells. The OR-BTZs also presented significant therapeutic efficacy and low systematic toxicity in the murine hepatocellular carcinoma model. To our knowledge, this study presents the first attempt to exploit the potential of oligoflavonoids for cancer cell-targeted drug delivery and will motivate the development of flavonoids and their derivatives as a new type of biomaterials for tumor-targeted therapy. |
| Databáze: | OpenAIRE |
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