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Polymeric micelles targeted against CD44v6 receptor increase niclosamide efficacy against colorectal cancer stem cells and reduce circulating tumor cells in vivo
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- Andrade, Fernanda (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.
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- Rafael, Diana (författare)
- 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.
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- Vilar-Hernandez, Mireia (författare)
- Univ Autonoma Barcelona, Mol Biol & Biochem Res Ctr Nanomed CIBBIM Nanomed, Vall dHebron Inst Recerca, Drug Delivery & Targeting Grp, Barcelona, Spain.
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- 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)
- Elsevier, 2021
- 2021
- Engelska.
- Ingår i: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 331, s. 198-212
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Polymeric micelles
- Niclosamide
- Colorectal cancer
- Cancer stem cells
- CD44v6
- Circulating tumor cells
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- ref (ämneskategori)
- art (ämneskategori)
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