單壁奈米碳管結合化療藥物SN-38與單株抗體 作為大腸癌標靶治療之藥用載體

Abstract

單壁奈米碳管作為奈米藥物載體結合喜樹鹼衍生物SN-38以及單株抗體爾必得舒Erbitux(c225) ，並探討以單壁奈米碳管作為藥物載體的藥物釋放、細胞途徑以及標靶治療之療效。 本論文中針對不同的表皮生長因子接受器(EGFR)表現量，選擇了三株大腸直腸癌細胞，分別是HCT116、HT29及SW620。其EGFR表現量的表現程度多寡:HCT116大於 HT29大於 SW620。此藥物載體針對這三株大腸直腸癌細胞皆能抑制50%以上的細胞存活率，並且EGFR表現程度愈高、愈能夠降低癌細胞存活率，其中EGFR表現量最高的HCT116之細胞存活率只剩10%。此奈米碳管藥物載體在一般生理環境pH 7.4 的藥物釋放率(20%)遠小於在h-CE (human carboxylesterase enzyme)羧酸酯酶中(80%) 及三株癌細胞的萃取蛋白中(60%)。此藥物載體利用C225主動標靶EGFR表現程度高之癌細胞，並藉由h-CE2 酶的調控在細胞內部大量釋放，達到控制藥物釋放(drug control release)。

Single-walled carbon nanotubes (SWNTs) combined with chemotherapeutic drug 7-Ethyl-10-hydroxy-camptothecin (SN-38) and monoclonal antibody Erbitux (C225) . The carriers were designed to explore the specific binding ability, anti-proliferation ability against to colorectal cancer cell lines and drug control release. The monoclonal antibody Erbitux (C225) bind to EGFR specifically. Therefore the subjects here were 3 kinds of colorectal cancer cell lines with different level of EGFR expression. EGFR expression level of these cells is: HCT116>HT29>SW620. SWNT25/pyCPY carrier reduce more than 50% cellular viability to all these 3 kinds of cells. Moreover the cell viability of EGFR over-expressing cell HCT116 is only 10%. The cellular viability is lower while the cell’s EGFR expression is higher. The anti-proliferation ability of SWNT25/py38 carrier is EGFR-depending and EGFR-Targeting. The drug control release process was designed to utilizing Human Carboxylesterase enzyme (hCE) to detach the SN-38 from SWNTs .This drug-release process is supposed by hCE would broke the ester bond link the SN-38 and Pyrene. The percentage of SN38 releasing from SWNTs carrier in physical environment pH7.4 buffer(20%) is much lower than cell lysate(60%) and hCE(80%). The SWNT25/py38 carrier using C225 specifically bind to EGFR expressing cell and releasing abundant SN38 to kill the cells.