Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
Show less -
Albuquerque, Lindomar J. C. [1, 2] ; Sincari, Vladimir [2] ; Jager, Alessandro [2] ; Kucka, Jan [2] ; Humajova, Jana [3] ; Pankrac, Jan [4] ; Paral, Petr [4] ; Heizer, Tomas [4] ; Janouskova, Olga [2] ; Davidovich, Irina [5, 6] ; Talmon, Yeshayahu [5, 6] ; Pouckova, Pavla [3] ; Stepanek, Petr [2] ; Sefc, Ludek [4] ; Hruby, Martin [2] ; Giacomelli, Fernando C. [1] ; Jager, Eliezer [2]
Total Authors: 17
Affiliation:
[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Ave Estados 5001, BR-09210580 Santo Andre - Brazil
[2] Acad Sci Czech Republ, Inst Macromol Chem, Heyrovskeho Nam 2, Prague 16206 6 - Czech Republic
[3] Charles Univ Prague, Fac Med 1, Inst Biophys & Informat, Salmovska 1, Prague 12000 - Czech Republic
[4] Charles Univ Prague, Fac Med 1, Ctr Adv Preclin Imaging CAPI, Salmovska 3, Prague 2 - Czech Republic
[5] Technion Israel Inst Technol, Dept Chem Engn, IL-3200003 Haifa - Israel
[6] Technion Israel Inst Technol, Russell Berrie Nanotechnol Inst RBNI, IL-3200003 Haifa - Israel
Total Affiliations: 6
Document type: Journal article
Source: JOURNAL OF CONTROLLED RELEASE; v. 332, p. 529-538, APR 10 2021.
Web of Science Citations: 0
Abstract

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 (PHPMA(35)-b-PDPA(75)). The self-assemblies were produced with desired size towards long circulation time and tumor accumulation (hydrodynamic diameter - D-H similar to 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 similar to 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. (AU)

FAPESP's process: 16/23844-8 - Biodegradable and pH-responsive polymersomes for gene and protein delivery
Grantee:Lindomar Jose Calumby Albuquerque
Support Opportunities: Scholarships in Brazil - Doctorate