Chemo-Sensitizer Conjugated Carbon Nanotubes as a Novel Cancer Therapeutical Delivery System

There are more than 10 million new diagnosed cancer incidences each year around the world. Conventional chemotherapy poses various side effects resulted in low specificity of chemo-reagent towards cancer cells. Carbon nanotubes (CNTs) can be functionalized to be more water-soluble, attached with specific drugs or fluorescent molecules, antibodies and therefore increase cancer cells targeting specificity. They display great potential in medical therapeutic applications. RRM2B, a small subunit of human ribonucleotide reductase, is suggested to play critical roles in DNA repair, DNA replication, mitochondrial homeostasis, and protection against cellular stress. Compatibly, cancer cells with depleted RRM2B level under stress resulted in higher death rate. Therefore, RRM2BsiRNA or RRM2BshRNA was proposed as a chemo and radiation-sensitizer in cancer treatment. In this study, RRM2BshRNA construct will firstly be applied in cancer cells to examine its sensitizer ability and the impacts in cell growth. Next, the sensitizer will be conjugated onto the CNTs with chemo-reagents and cancer cells specific antibody (anti-EGFR antibody). The sensitizer effects of RRM2BshRNA/CNT in different cancer cells under stress will be demonstrated. Also, functionally linked RRM2BshRNA/CNT to chemo-reagents (HDAC inhibitor and DNMT inhibitor) and antibody for cancer cell specific targeting platform will be set up. At the end, the xenograft mice model will be applied to examine the cancer cells targeting and killing effects of this novel platform in vivo. The goal of this project is to set up the chemo-sensitizer conjugated carbon nanotubes as a novel cancer therapeutical delivery system. This cross-field collaborating project is expected to bring us a multi-functional nanomedical delivery platform that would improve cancer killing effect, increase cancer targeting specificity, and greatly benefit future cancer therapy.