Targeting colorectal cancer cells with single-walled carbon nanotubes conjugated to anticancer agent SN-38 and EGFR antibody.
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.
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan.
Pei-Chi
PC
Lee
Yu-Chi
YC
Chiou
Jau-Min
JM
Wong
Cheng-Liang
CL
Peng
Ming-Jium
MJ
Shieh
D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D043182:Carboxylesterase / Q000378:metabolism; D045744:Cell Line, Tumor; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D000077146:Irinotecan; D018613:Microscopy, Confocal; D037742:Nanotubes, Carbon / Q000737:chemistry*
D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D018796:Immunoconjugates; D037742:Nanotubes, Carbon; D000077146:Irinotecan; C512478:EGFR protein, human; D066246:ErbB Receptors; D043182:Carboxylesterase; D000068818:Cetuximab; D002166:Camptothecin
C225; EGFR; Human carboxylesterase enzyme; SN38; Single-walled carbon nanotubes