Targeting Colorectal Cancer Stem-Like Cells with Anti-CD133 Antibody-Conjugated SN-38 Nanoparticles

Abstract

Cancer stem-like cells play a key role in tumor development, and these cells are relevant to the failure of conventional chemotherapy. To achieve favorable therapy for colorectal cancer, PEG-PCL-based nanoparticles, which possess good biological compatibility, were fabricated as nanocarriers for the topoisomerase inhibitor, SN-38. For cancer stem cell therapy, CD133 (prominin-1) is a theoretical cancer stem-like cell (CSLC) marker for colorectal cancer and is a proposed therapeutic target. Cells with CD133 overexpression have demonstrated enhanced tumor-initiating ability and tumor relapse probability. To resolve the problem of chemotherapy failure, SN-38-loaded nanoparticles were conjugated with anti-CD133 antibody to target CD133-positive (CD133(+)) cells. In this study, anti-CD133 antibody-conjugated SN-38-loaded nanoparticles (CD133Ab-NPs-SN-38) efficiently bound to HCT116 cells, which overexpress CD133 glycoprotein. The cytotoxic effect of CD133Ab-NPs-SN-38 was greater than that of nontargeted nanoparticles (NPs-SN-38) in HCT116 cells. Furthermore, CD133Ab-NPs-SN-38 could target CD133(+) cells and inhibit colony formation compared with NPs-SN-38. In vivo studies in an HCT116 xenograft model revealed that CD133Ab-NPs-SN-38 suppressed tumor growth and retarded recurrence. A reduction in CD133 expression in HCT116 cells treated with CD133Ab-NPs-SN-38 was also observed in immunohistochemistry results. Therefore, this CD133-targeting nanoparticle delivery system could eliminate CD133-positive cells and is a potential cancer stem cell targeted therapy.

Colorectal cancer stem cells: a review of targeted drug delivery by gold nanoparticles

“…glycol)-poly(3-caprolactone) (mPEG-PCL) nanoparticles loaded with anticancer drug 7-ethyl-10-hydroxy-camptothecin (SN-38). 33 The in vitro and in vivo studies showed that CD133targeting nanoparticles have increased cytotoxicity and inhibited tumor growth in HCT116 cells and mouse xenogra models, respectively, compared with the none antibody-targeted nanoparticles. In this case, the therapeutic effects on CRC have been enhanced by the CD133 antibody conjugates because the chemotherapeutic agent SN-38 is efficiently guided to the overexpressed CD133 markers at the tumor site.…”

Using of keratin substrate for enrichment of HT29 colorectal cancer stem‐like cells

“…In this study, the influence of keratin substrate on the formation of HT29 spheroid‐like structures with stem cell properties was investigated. To this end, we evaluated and characterized the formation of sphere‐like structures and expression of CD133, as a specific surface marker of colorectal CSLCs,, and stemness‐related genes on keratin in comparison to collagen substrate. To the best of our knowledge, this is the first report on using keratin substrate for CSLCs’ enrichment.…”

Panitumumab‐Conjugated Pt‐Drug Nanomedicine for Enhanced Efficacy of Combination Targeted Chemotherapy against Colorectal Cancer

“…With the present NANO Pt‐Pan preparation, Panitumumab–EGFR binding facilitates targeted uptake into EGFR overexpressing CRC cells. Unlike other ligand‐modified nanomedicines with enhanced cell/tumor uptake, Panitumumab in NANO Pt‐Pan can suppress EGFR activation in CRC cells, thus improving antiproliferative effects and Pt drug efficacy. Moreover, NANO Pt‐Pan likely protects the Pt drug from degradation, resulting in increased circulation times and greater uptake into CRC cells.…”