Description: According to the latest report carried out by WHO in 2012, 15% of worldwide death came from cancer, ranking the second leading cause of death (following cardiovascular diseases) and causing more than AIDS, tuberculosis, and malaria combined. Traditional treatments vary from surgery, radiation, to chemotherapy. While surgeries have low prognosis, patients treated by radiation and/or chemotherapy show fragile health since these treatments damaged normal cells in their body, also leading to the weaken for immune system. Nowadays, clinical trials broaden their way to immune therapy, hormone therapy, and targeted therapy. Since they're general treatments for the whole body, the first two therapies get their obstacles on side effects. Thus, a drug targeting a specific molecule that functions in cancer growth or metastasis can be an ideal choice for further exploration. Inspired by these facts, our project aims at building a simple transplantable drug system based on targeted cancer treating.By packing gene-specific drugs into modified exosomes, we can deliver them into a certain part of our body without interfering any irrelevant tissues. And by including small interfering RNAs (siRNAs) to exosomes, targeted gene expression will be decreased or eradicated in the transcription level. Based on work published in 2010, systemic injection of iRGD, a previously characterized tumor-penetrating peptide, showed great help on drug treatments of mouse tumor, regardless of compositions of drugs. To build the drug-treating system, we modified our exosomes with iRGD, which acted as a targeting tool, and for the oncogene-silencing part, we took EGFR as a target gene for siRNAs’ function verification. Validation goes into two parts – one for the targeting and the other for the silencing, and for each part, both in vivo and in vitro sections are carried out. By chasing fluorescence signals from exosomes and siRNA in vitro, we demonstrated that iRGD-modified exosomes loading with EGFR-specific siRNAs (siRNA-iRGD-exosomes) efficiently got into the tumor cells, compared with other normal ones. Also, in vivo imaging showed specific distribution of dyes in mice, indicated our siRNA-iRGD-exosomes traveled and finally reached the mice tumor tissues. Through experiments analyzing the expression level of EGFR and index of apoptosis, significant changes after siRNA-iRGD-exosomes treatment are expected.
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Year: 2016Visit Wiki
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Updated at: 8/9/16