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pH-responsive polymersome-mediated delivery of doxorubicin into tumor sites enhances the therapeutic efficacy and reduces cardiotoxic effects
LJC. Albuquerque, V. Sincari, A. Jäger, J. Kucka, J. Humajova, J. Pankrac, P. Paral, T. Heizer, O. Janouškova, I. Davidovich, Y. Talmon, P. Pouckova, P. Štěpánek, L. Sefc, M. Hruby, FC. Giacomelli, E. Jäger
Jazyk angličtina Země Nizozemsko
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- doxorubicin * terapeutické užití MeSH
- kardiotoxicita MeSH
- koncentrace vodíkových iontů MeSH
- lékové transportní systémy MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové mikroprostředí MeSH
- nádory * farmakoterapie MeSH
- nosiče léků terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
Citace poskytuje Crossref.org
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- $a Albuquerque, Lindomar J C $u Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovského nám. 2, 162 06 Prague 6, Czech Republic; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Avenida dos Estados 5001, Santo André 09210-580, Brazil. Electronic address: lindomar.albuquerque@ufabc.edu.br
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- $a 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.
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