서강대학교

초록/요약

Circulating tumor cells (CTCs) are emerging biomarkers, especially in case of liquid biopsy, and important indicator for prognosis monitoring in case of personalized anticancer therapy. CTC analysis is a promising diagnostic method for estimating the risk of metastatic relapse and metastatic progression in patient with cancer. The basic problem of CTC study is their extremely low inherent numbers in blood (around one CTC per 109 non cancerous hematopoietic cells). Hence, before detection or characterization of CTCs their isolation is important. A subpopulation of CTCs with stem-like behavior are known as stem-like circulating tumor cells (SCTCs). In recent years stem like cancer cells (SCCs) hypothesis has attracted great attention in the field of cancer biology. According to the concept, a minor population of the cancer cells work as SCCs or tumor initiating cells (TICs), is able to self renew. Due to their stemness, the SCCs lead to the generation of more SCCs and able to differentiate a varirty of cells in the tumor. It is assumed that SCCs are responsible for resistance to current chemotherapy or radiotherapy. Furthermore, they could play a crucial role in distant metstasis. To increase the therapeutic efficacy targeting of SCCs are important. Hence, it is important to characterize the SCCs and distinguish them from tumor cells or CTCs. On the other hand, some intracelular biomarkers, such as microRNA (miRNA) are found to be dysregulated in many cancers, such as breast, prostate, colon and lung. Therefore, microRNAs can work as onco- miRNAs or tumor suppressor miRNAs depending on their respective target genes. miRNAs are able to modulate the sensitivity of cancer cells to chemotherapeutic drugs. miRNAs can regulate epithelial to mesenchymal transition (EMT). Loss of miRNA may changes the tumor cells to chemoresistant phenotypes. Therefore, through measuring miRNA expression it is possible to charactertize and distinguishes the epithelial or mesenchymal type of cancer cells, as well as to distinguish chemosensitive or chemoresistant phenotype. For effective chemotherapy targeted drug drug delivery is important. A lot of nanocarriers have been developed for efficient delivery of therapeutic agents. Nanoparticle based drug delivery has several advantages, particularly at the systemic level including longer circulation half-lives, improved pharmacokinetics and reduced side effects. But the challenges are; preparation of functionalized stable nanoparticles, payload capability, targeted delivery, uptake efficiency by the targeted cells and efficient drug release. In this study, we developed 3 kinds of multifunctional conjugated nanoparticles for in situ characterization of CTCs, distinguishing SCTCs from CTCs, distinguishing chemosensitive or chemoresistant phenotypes of cancer cells and for targeted delivery of chemotherapeutic agent. First one coposed of colloidal gold nanoparticles (AuNP) Raman reporter, heterofunctional polyethylene glycol (PEG), antibody and DNA for efficient capturing and in-situ characterization of breast CTCs, as well as distinguishing SCTCs from CTCs. The second one consists of AuNP, Raman reporter and complementary half miRNA for distinguishing chemosensitive or chemoresistant phenotypes of cancer cells. The third one constituted with AuNP, anticancer drug (doxorubicin), cell penetrating peptide (CPP), PEG and antibody for efficient delivery of anticancer drug to the target cells.