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

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CONTROLLED RELEASE; v. 332, p. 529-538, APR 10 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 16/23844-8 - Vesículas poliméricas biodegradáveis e sensíveis ao pH para encapsulação de BIOMACROMOLÉCULAS
• Beneficiário: Lindomar Jose Calumby Albuquerque
• Modalidade de apoio: Bolsas no Brasil - Doutorado