pH-responsive polymersome-mediated delivery of doxorubicin into tumor sites enhances the therapeutic efficacy and reduces cardiotoxic effects
| Autor: | Lindomar J. C. Albuquerque, Petr Štěpánek, Tomáš Heizer, Martin Hruby, Petr Paral, Vladimir Sincari, Pavla Pouckova, Jan Kučka, Ludek Sefc, Eliézer Jäger, Olga Janoušková, Yeshayahu Talmon, Jana Humajova, Irina Davidovich, Fernando C. Giacomelli, Alessandro Jäger, Jan Pankrác |
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| Rok vydání: | 2021 |
| Předmět: |
Drug
media_common.quotation_subject Pharmaceutical Science 02 engineering and technology Pharmacology Mice 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems Neoplasms Tumor Microenvironment medicine Animals Methacrylamide Doxorubicin 030304 developmental biology media_common Drug Carriers 0303 health sciences Cardiotoxicity Tumor microenvironment Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Mice Inbred C57BL chemistry Polymersome Nanomedicine Female Growth inhibition 0210 nano-technology medicine.drug |
| Zdroj: | Journal of Controlled Release. 332:529-538 |
| ISSN: | 0168-3659 |
| Popis: | The delivery of therapeutics into sites of action by using cargo-delivery platforms potentially minimizes their premature degradation and fast clearance from the bloodstream. Additionally, drug-loaded stimuli-responsive supramolecular assemblies can be produced to respond to the inherent features of tumor microenvironments, such as extracellular acidosis. We report in this framework the use of pH-responsive polymersomes (PSs) manufactured using poly([N-(2-hydroxypropyl)] methacrylamide)35-b-poly[2-(diisopropylamino)ethyl methacrylate]75 as the building unit (PHPMA35-b-PDPA75). The self-assemblies were produced with desired size towards long circulation time and tumor accumulation (hydrodynamic diameter - DH ~ 100 nm), and they could be successfully loaded with 10% w/w DOX (doxorubicin), while maintaining colloidal stability. The DOX loaded amount is presumably mainly burst-released at the acidic microenvironment of tumors thanks to the pH-switchable property of PDPA (pKa ~ 6.8), while reduced drug leakage has been monitored in pH 7.4. Compared to the administration of free DOX, the drug-loaded supramolecular structures greatly enhanced the therapeutic efficacy with effective growth inhibition of EL4 lymphoma tumor model and 100% survival rate in female C57BL/6 black mice over 40 days. The approach also led to reduced cardiotoxic effect. These features highlight the potential application of such nanotechnology-based treatment in a variety of cancer therapies where low local pH is commonly found, and emphasize PHPMA-based nanomedicines as an alternative to PEGylated formulations. |
| Databáze: | OpenAIRE |
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