Enhanced Antitumor Efficacy through an 'AND gate' Reactive Oxygen-Species-Dependent pH-Responsive Nanomedicine Approach
| Autor: | Martin Hrubý, Rafał Konefał, Alessandro Jäger, Martijn Verdoes, Ewa Pavlova, Eliézer Jäger, Jana Humajova, Yusuf Dolen, Carl G. Figdor, Tomáš Heizer, Jan Kučka, Jan Pankrác, Luděk Šefc |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
Biomedical Engineering Pharmaceutical Science 02 engineering and technology 010402 general chemistry 01 natural sciences Biomaterials Mice Drug Delivery Systems Side chain Extracellular medicine Animals Doxorubicin Micelles chemistry.chemical_classification Reactive oxygen species Tumor microenvironment Drug Carriers Chemistry Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology 0104 chemical sciences Oxygen Nanomedicine Drug delivery Polymersome Biophysics Nanoparticles 0210 nano-technology Reactive Oxygen Species Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] medicine.drug |
| Zdroj: | Advanced Healthcare Materials, 10, 13 Advanced Healthcare Materials, 10 Adv Healthc Mater |
| ISSN: | 2192-2640 |
| Popis: | Contains fulltext : 244600.pdf (Publisher’s version ) (Open Access) Anticancer drug delivery strategies are designed to take advantage of the differential chemical environment in solid tumors independently, or to high levels of reactive oxygen species (ROS) or to low pH, compared to healthy tissue. Here, the design and thorough characterization of two functionalizable "AND gate" multiresponsive (MR) block amphiphilic copolymers are reported, aimed to take full advantage of the coexistence of two chemical cues-ROS and low pH-present in the tumor microenvironment. The hydrophobic blocks contain masked pH-responsive side chains, which are exposed exclusively in response to ROS. Hence, the hydrophobic polymer side chains will undergo a charge shift in a very relevant pH window present in the extracellular milieu in most solid tumors (pH 5.6-7.2) after demasking by ROS. Doxorubicin (DOX)-loaded nanosized "AND gate" MR polymersomes (MRPs) are fabricated via microfluidic self-assembly. Chemical characterization reveals ROS-dependent pH sensitivity and accelerated DOX release under influence of both ROS and low pH. Treatment of tumor-bearing mice with DOX-loaded nonresponsive and "AND gate" MRPs dramatically decreases cardiac toxicity. The most optimal "AND gate" MRPs outperform free DOX in terms of tumor growth inhibition and survival, shedding light on chemical requirements for successful cancer nanomedicine. |
| Databáze: | OpenAIRE |
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