Targeting colorectal cancer cells with single-walled carbon nanotubes conjugated to anticancer agent SN-38 and EGFR antibody
Journal
Biomaterials
Journal Volume
34
Journal Issue
34
Pages
8756-8765
Date Issued
2013
Author(s)
Abstract
In this study, single-walled carbon nanotubes (SWNTs) conjugated with antibody C225 were used to achieve targeted therapy against EGFR over-expressed colorectal cancer cells. In addition, the control release of the chemotherapeutic drug, 7-Ethyl-10-hydroxy-camptothecin (SN38), was studied. We used three different colorectal cancer cell lines, HCT116, HT29, and SW620, listed in the order of decreasing expression levels of EGFR. Our results showed that SWNT could use C225 to specifically bind to EGFR-expressed cells. The cellular uptakes of SWNT of EGFR over-expressed cells (HCT116 and HT29) were much higher than that of the negative control (SW620). We, next, demonstrated that receptor-mediated endocytosis was the primary cell entry route for SWNT. As a consequence, abundant amount of SN38 was released and EGFR over-expressed cells were killed. The drug control release process was studied by utilizing human carboxylesterase enzyme (hCE) that would break the bond linking SN38 and SWNT-carrier in cytoplasm. The intracellular SN38 release observed by confocal microscopy showed that SN38 actually dissociated from the SWNT-carrier first. SN38's entry to nucleus was then followed while the SWNT-carrier still remained in the cytoplasm. Overall, all these data suggested that SWNT could be a good carrier for targeting controlled release therapy. ? 2013 Elsevier Ltd.
Subjects
C225; EGFR; Human carboxylesterase enzyme; Single-walled carbon nanotubes; SN38
SDGs
Other Subjects
C225; Carboxylesterases; Chemotherapeutic drugs; Colorectal cancer cell; EGFR; Receptor-mediated endocytosis; Single-walled carbon nanotube (SWNTs); SN38; Antibodies; Cell culture; Diseases; Enzymes; Molecular biology; Single-walled carbon nanotubes (SWCN); Cells; carboxylesterase; cetuximab; epidermal growth factor receptor; firtecan; single walled nanotube; article; cancer cell; cancer cell culture; chemical bond; colorectal cancer; confocal microscopy; controlled drug release; controlled study; cytoplasm; dissociation; drug conjugation; drug delivery system; drug synthesis; endocytosis; enzyme activity; gene expression; gene overexpression; human; human cell; in vitro study; mediator; molecularly targeted therapy; priority journal; protein function; C225; EGFR; Human carboxylesterase enzyme; Single-walled carbon nanotubes; SN38; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Phytogenic; Apoptosis; Camptothecin; Carboxylesterase; Cell Line, Tumor; Colorectal Neoplasms; Delayed-Action Preparations; Drug Carriers; HCT116 Cells; HT29 Cells; Humans; Immunoconjugates; Microscopy, Confocal; Nanotubes, Carbon; Receptor, Epidermal Growth Factor
Type
journal article