STUDYING THE MIR-24 EXPRESSION PROFILE IN BREAST CARCINOMAS AND SYNTHESIS OF LIPOSOMES AS NANOVEHICLES FOR SIRNA BASED FUTURE ONCOTHERAPEUTICS

Abstract

Breast cancer related mortalities are currently on the rise and hence the need for model therapeutics to improve survival and quality of life in patients is a prime necessity. Much of the prognosis and tumour behaviour in patients are controlled by the cancer stem cells, which ultimately leads to chemotherapeutic resistance and disease recurrence. MiRNA are short non-coding RNAs with potential roles in carcinogenesis and mRNA silencing. miRNA-24 could be a probable regulator of epithelial to mesenchymal transition (EMT) mediated via Klf-8 and Notch-1. However, the exact mechanism for miR-24, Klf-8 and Notch-1 mediated EMT remains obscure. EMT is a hallmark of highly metastatic and devastating tumours and reversing the process of EMT could be a potent strategy towards developing favouring therapeutics in high-grade breast carcinomas. However, it is necessary to optimally deliver miRNA inhibitors such as siRNAs (small interfering RNAs) to the afflicted cells in order to reverse or limit the process of EMT. Liposomes and alginate-chitosan gels could be potential candidates owing to their nano dimensions and the probability of using these nano particles for combinatorial therapy remains an august possibility. Nevertheless, further experiments shall be needed first to establish a concrete mechanism and then to synthesize an optimal vector for siRNA trafficking. Dual targeting of tumour cells could then be possible with two tier liposome-alginate nanostructures Under the scope of this thesis, an attempt has been made to identify and delve one such probable EMT modulating miRNA, miR-24 in breast cancer. In addition to this liposomes and gels have been fabricated, which could in future serve as potential candidates of two tier architecture for drug delivery in breast cancers.