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  • Andrade, FernandaUniv Porto, i3S Inst Invest & Inovacao Saude, Rua Alfredo Allen 208, Porto, Portugal.;Univ Porto, INEB Inst Nacl Engn Biomed, Rua Alfredo Allen 208, P-4200180 Porto, Portugal.;Univ Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain. (författare)

Polymeric micelles targeted against CD44v6 receptor increase niclosamide efficacy against colorectal cancer stem cells and reduce circulating tumor cells in vivo

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • Elsevier,2021
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-441976
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-441976URI
  • https://doi.org/10.1016/j.jconrel.2021.01.022DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Colorectal cancer (CRC) is a highly prevalent disease worldwide. Patient survival is hampered by tumor relapse and the appearance of drug-resistant metastases, which are sustained by the presence of cancer stem cells (CSC). Specific delivery of anti-CSC chemotherapeutic drugs to tumors by using targeted drug delivery systems that can also target CSC sub-population might substantially improve current clinical outcomes. CD44v6 is a robust biomarker for advanced CRC and CSC, due to its functional role in tumorigenesis and cancer initiation process. Here, we show that CD44v6-targeted polymeric micelles (PM) loaded with niclosamide (NC S), a drug against CSC, is a good therapeutic strategy against colorectal CSC and circulating tumor cells (CTC) in vivo. HCT116 cells were sorted according to their CD44v6 receptor expression into CD44v6+ (high) and CDv44v6- (low) subpopulations. Accordingly, CD44v6+ cells presented stemness properties, such as overexpression of defined stemness markers (ALDH1A1, CD44v3 and CXCR4) and high capacity to form colonspheres in low attachment conditions. NC S-loaded PM functionalized with an antibody fragment against CD44v6 (Fab-CD44v6) presented adequate size, charge, and encapsulation efficiency. In addition, Fab-CD44v6 significantly increased PM internalization in CD44v6+ cells. Further, encapsulation of NCS improved its effectiveness in vitro, particularly against colonspheres, and allowed to increase its intravenous dosage in vivo by increasing the amount of NCS able to be administered without causing toxicity. Remarkably, functionalized PM accumulate in tumors and significantly reduce CTC in vivo. In conclusion, CD44v6 targeted PM meet the essential conditions to become an efficient anti-CSC therapy.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Rafael, DianaUniv Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain.;Inst Salud Carlos III, Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Zaragoza, Spain. (författare)
  • Vilar-Hernandez, MireiaUniv Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain. (författare)
  • Montero, SaraUniv Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain.;Inst Salud Carlos III, Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Zaragoza, Spain. (författare)
  • Martinez-Trucharte, FrancescUniv Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain. (författare)
  • Seras-Franzoso, JoaquinUniv Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain. (författare)
  • Diaz-Riascos, Zamira, VUniv Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain.;Univ Autonoma Barcelona, Vall dHebron Inst Recerca, CIBBIM Nanomed, Funct Validat & Preclin Res FVPR, Barcelona, Spain. (författare)
  • Boullosa, AnaUniv Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain.;Univ Autonoma Barcelona, Vall dHebron Inst Recerca, CIBBIM Nanomed, Funct Validat & Preclin Res FVPR, Barcelona, Spain. (författare)
  • Garcia-Aranda, NataliaUniv Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain.;Univ Autonoma Barcelona, Vall dHebron Inst Recerca, CIBBIM Nanomed, Funct Validat & Preclin Res FVPR, Barcelona, Spain. (författare)
  • Camara-Sanchez, PatriciaUniv Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain.;Univ Autonoma Barcelona, Vall dHebron Inst Recerca, CIBBIM Nanomed, Funct Validat & Preclin Res FVPR, Barcelona, Spain. (författare)
  • Arango, DiegoUniv Autonoma Barcelona, Vall dHebron Res Inst, CIBBIM Nanomed, Biomed Res Digest Tract Tumors Grp, Barcelona, Spain. (författare)
  • Nestor, Marika,1976-Uppsala universitet,Medicinsk strålningsvetenskap(Swepub:uu)manes424 (författare)
  • Abasolo, IbaneUniv Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain.;Inst Salud Carlos III, Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Zaragoza, Spain.;Univ Autonoma Barcelona, Vall dHebron Inst Recerca, CIBBIM Nanomed, Funct Validat & Preclin Res FVPR, Barcelona, Spain. (författare)
  • Sarmento, BrunoUniv Porto, i3S Inst Invest & Inovacao Saude, Rua Alfredo Allen 208, Porto, Portugal.;Univ Porto, INEB Inst Nacl Engn Biomed, Rua Alfredo Allen 208, P-4200180 Porto, Portugal.;Inst Invest & Formacao Avancada Ciencias & Tecnol, CESPU, Rua Cent Gandra 1317, P-4585116 Gandra, Portugal. (författare)
  • Schwartz, Simo, Jr.Univ Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain.;Inst Salud Carlos III, Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Zaragoza, Spain. (författare)
  • Univ Porto, i3S Inst Invest & Inovacao Saude, Rua Alfredo Allen 208, Porto, Portugal.;Univ Porto, INEB Inst Nacl Engn Biomed, Rua Alfredo Allen 208, P-4200180 Porto, Portugal.;Univ Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain.Univ Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain.;Inst Salud Carlos III, Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Zaragoza, Spain. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Controlled Release: Elsevier331, s. 198-2120168-36591873-4995

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