Efficacy Evaluation of Newly Designed Multifunctional Nanoagents with SN38 against Colorectal Cancer

• Main Authors: Ming-Hsien Tsai, 蔡銘賢
• Other Authors: 謝銘鈞
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/4y6h68

博士 === 國立臺灣大學 === 醫學工程學研究所 === 106 === Part I: Several types of nano-sized anti-cancer agents that could increase the accumulation of drugs in the tumor site have been created and developed for enhancing efficacy of chemotherapeutic drugs in colon cancer treatment. In addition, to achieve the optimal cancer chemotherapeutic efficacy, nano-sized agents with specific functions were designed to efficiently kill cancer cells. The ideal nano-sized agent must be able to successfully release the drug and result in an increased cellular uptake of the chemotherapeutic drug. Our research team focused on two important functions, drug release and targeting functions, thus targeting functional micelles which were designed to possess disulfide bonds and entrapped much chemotherapeutic drug, 7-ethyl-10-hydroxy-camptothecin (SN38), which was created as a powerful candidate for an ideal anti-cancer drug for colon cancer treatment. In particular, Self-Breakable SN38-loaded micelles (SN/38 micelles), Non-Breakable micelles SN38-loaded (NB/38 micelles) and Folate-decorated Self-Breakable SN38-loaded micelles (FSB/38 micelles) were prepared and tested to the designed agents. The results showed that the folate-decorated functional micelles with disulfide bonds could be an effective chemotherapeutic agent for colon cancer treatment. Part II: Cancer researches regarding near-infrared(NIR) agents for chemothermal therapy(CTT) have shown that agents with specific functions are able to inhibit tumor growth. The aim of current study was to optimize CTT efficacy for treatment of colorectal cancer(CRC) by exploring strategies which can localize high temperature within tumors and maximize chemotherapeutic drug uptake. We designed a new and simple multifunctional NIR nanoagent composed of the NIR cyanine dye, polyethylene glycol, and a cyclic arginine-glycine-aspartic acid peptide and loaded with the anti-CRC chemotherapeutic agent, 7-ethyl-10-hydroxy-camptothecin(SN38). Each component of this nanoagent exhibited its specific functions that help boost CTT efficacy. The results showed that this nanoagent greatly strengthen the efficacy of SN38 and CTT againstCRC due to its NIR imaging ability, photothermal, enhanced permeability and retention(EPR) effect, reticuloendothelial system avoidance, and angiogenic blood vessel-targeting properties. This NIR nanoagent will help facilitate development of new strategies for treating CRC.