pH-responsive polymersome-mediated delivery of doxorubicin into tumor sites enhances the therapeutic efficacy and reduces cardiotoxic effects

0541439 - ÚMCH 2022 RIV NL eng J - Journal Article
Calumby Albuquerque, Lindomar J. - Sincari, Vladimir - Jäger, Alessandro - Kučka, Jan - Humajová, J. - Pankrác, J. - Páral, P. - Heizer, T. - Janoušková, Olga - Davidovich, I. - Talmon, Y. - Pouckova, P. - Štěpánek, Petr - Šefc, L. - Hrubý, Martin - Giacomelli, F. C. - Jäger, Eliezer
pH-responsive polymersome-mediated delivery of doxorubicin into tumor sites enhances the therapeutic efficacy and reduces cardiotoxic effects.
Journal of Controlled Release. Roč. 332, 10 April (2021), s. 529-538. ISSN 0168-3659. E-ISSN 1873-4995
R&D Projects: GA ČR(CZ) GJ20-15077Y; GA ČR(CZ) GJ20-13946Y; GA MŠMT(CZ) LM2018133; GA MŠMT(CZ) LO1507; GA MŠMT(CZ) LTC19032
Research Infrastructure: Czech-BioImaging II - 90129
Institutional support: RVO:61389013
Keywords : nanomedicine * pH-responsive polymersomes * doxorubicin
OECD category: Polymer science
Impact factor: 11.467, year: 2021
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/pii/S0168365921001243?via%3Dihub

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 approximately 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 approximately 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.
Permanent Link: http://hdl.handle.net/11104/0318997