EpCAM aptamer-functionalized polydopamine-coated mesoporous silica nanoparticles loaded with DM1 for targeted therapy in colorectal cancer

Abstract

Yang Li,1,* Yanhong Duo,2,3,* Shiyun Bao,1 Lisheng He,4 Kai Ling,5 Jinfeng Luo,4 Yue Zhang,1 Hao Huang,2 Han Zhang,2 Xiaofang Yu1 1Department of Hepatobiliary and Pancreas Surgery, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, 2Shenzhen Engineering Laboratory of Phosphorene and Optoelectronics, Collaborative Innovation Center for Optoelectronic Science and Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 3Key Laboratory of Plant Cell Activities and Stress Adaptation, Ministry of Education, School of Life Sciences, Lanzhou University, Lanzhou, 4Department of Pathology, 5Institute of Respiratory Diseases, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, China *These authors contributed equally to this work Abstract: DM1, a maytansine derivative, is a highly potential cytotoxic agent but with severe side effects; therefore, its application in clinical cancer therapy is limited. Here, in order to mitigate this intrinsic drawback of DM1, we developed mesoporous silica nanoparticles (MSNs) loaded with DM1 and surface-decorated with hydrochloride dopamine (PDA), polyethylene glycol (PEG), and epithelial cell adhesion molecule (EpCAM) aptamer (APt) for the targeted treatment of colorectal cancer (CRC). In this system, the PDA coating could be used as pH-sensitive gatekeepers to control the release of DM1 from MSNs in response to the pH stimulus and EpCAM APt-guided active targeting enables the increased delivery of DM1 to CRC as well as a reduction in toxicity and side effects by minimizing the exposure of normal tissues to DM1. Results demonstrated that DM1 inhibited the formation of microtubules and induced apoptosis in tumor cells via caspase signaling. In comparison with the control groups, the MSNs-DM1@PDA-PEG-APt bioconjugates exhibited increased binding ability and much higher cytotoxicity to the CRC SW480 cell line. Furthermore, in vivo assays confirmed the advantages of such a strategy. These findings suggested that MSNs-DM1@PDA-PEG-APt could represent a promising therapeutic platform for EpCAM-positive CRC. Keywords: DM1, EpCAM aptamer, mesoporous silica nanoparticles, colorectal cancer

Keywords

• DM1
• EpCAM aptamer
• mesoporous silica nanoparticles
• colorectal cancer