Thioether-Based Polymeric Micelles with Fine-Tuned Oxidation Sensitivities for Chemotherapeutic Drug Delivery
| Autor: | Masoud Ghasemi, Bin Liu, Enrique D. Gomez, Urara Hasegawa, André J. van der Vlies, Jiayi Xu, Amanda Bell, Brett Rosoff-Verbit, Carol M. Bator |
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| Rok vydání: | 2021 |
| Předmět: |
Polymers and Plastics
Cell Survival Substituent Bioengineering Sulfides Micelle Redox Article Biomaterials chemistry.chemical_compound Drug Delivery Systems Thioether Materials Chemistry Humans Reactivity (chemistry) Hydrogen peroxide Micelles Drug Carriers Endothelial Cells Hydrogen Peroxide Hydrogen-Ion Concentration Combinatorial chemistry Drug Liberation Thiomorpholine chemistry Doxorubicin Drug delivery |
| Zdroj: | Biomacromolecules |
| ISSN: | 1526-4602 |
| Popis: | Oxidation-sensitive drug delivery systems (DDS) have attracted attention due to the potential to improve efficacy and safety of chemotherapeutics. These systems are designed to release the payload in response to oxidative stress conditions, which are associated with many types of cancer. Despite extensive research on the development of oxidation-sensitive DDS, the lack of selectivity towards cancer cells over healthy cells remains a challenge. Here, we report the design and characterization of polymeric micelles containing thioether groups with varying oxidation sensitivities within the micellar core, which become hydrophilic upon thioether oxidation leading to destabilization of the micellar structure. We first used the thioether model compounds, 3-methylthiopropylamide (TPAM), thiomorpholine amide (TMAM), and 4-(methylthio)benzylamide (TPhAM), to investigate the effect of the chemical structures of the thioethers on the oxidation by hydrogen peroxide [Formula: see text]. TPAM shows the fastest oxidation followed by TMAM and TPhAM, showing that the oxidation reaction of thioethers can be modulated by changing the substituent groups bound to the sulfur atom. We next prepared micelles containing these different thioether groups within the core (TP, TM and TPh micelles). The micelles containing the thioether groups with a higher oxidation sensitivity were destabilized by [Formula: see text] at lower concentration. Micelle destabilization was also tested in human liver cancer (HepG2) cells and human umbilical vein endothelial cells (HUVECs). The TP micelles having the highest oxidation sensitivity were destabilized in both HepG2 cells and HUVECs while the TPh micelles, which showed the lowest reactivity towards [Formula: see text] , were stable in those cell lines. The TM micelles possessing a moderate oxidation sensitivity were destabilized in HepG2 cells but were stable in HUVECs. Furthermore, the micelles were loaded with doxorubicin (Dox) to evaluate their potential in drug delivery applications. Among the micelles, the TM micelles loaded with Dox showed the enhanced relative toxicity in HepG2 cells over HUVECs. Therefore, our approach to fine-tune the oxidation sensitivity of the micelles has potential for improving therapeutic efficacy and safety of drugs in cancer treatment. |
| Databáze: | OpenAIRE |
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