PhD Oral Qualifying Examination : Targeted drug delivery for non-muscle invasive bladder cancer

Speaker Mullapudi Sneha Sree (Supervisor: Prof Neoh Koon Gee)

Host Department of Chemical and Biomolecular Engineering

Date/Time 14 Dec - 14 Dec, 4.00pm

Venue E5-02-32 , Faculty of Engineering, National University of Singapore

Synopsis

Bladder cancer (BC) is the ninth most common malignancy worldwide and its treatment is one of the costliest on a per patient basis due to its frequent recurrence rate. Intravesical chemotherapy, which involves direct instillation of drugs into the bladder, is one of the most popular treatments for bladder tumors. However, the main challenges yet to be addressed in this type of therapy are the short retention time of the drugs in the bladder due to urine voiding and the lack of specificity of the drug or carrier towards the cancer cells. To overcome these challenges, drug delivery systems which facilitate targeted delivery of drugs directly to cancer sites and which can enhance internalization of the drugs into the cells are highly desired. As such, this PhD work aims to develop various ways to achieve targeted drug delivery for non-muscle invasive BCs. We have shown that CD47, EGFR and FGFR3 are overexpressed on BC cells, and the peptides (txCD47, txEGFR and txFGFR3) that can target these receptors have been selected for our work. Our results indicate that peptide-conjugated docetaxel (txCD47-DTX, txEGFR-DTX and txFGFR3-DTX) showed higher killing efficacy at lower DTX concentrations compared to free drug at the same concentration. In the second system investigated, txCD47-conjugated maleimide-modified bovine serum albumin (txCD47-BSA) used as a carrier for DTX was shown to greatly enhance the killing efficacy of DTX. Going forward, the txCD47-BSA carrier will be tested with mitomycin C (MMC), and the possibility of synergism between DTX and MMC will be investigated. The possibility of using glucose as a targeting agent will also be explored since the facilitative glucose transporter 1 (GLUT1) is overexpressed in BC cells. Since hyperthermia is of interest in BC therapy, the effect of temperature on the efficacy of the targeted delivery systems will be evaluated. Finally, the efficacy of best performing in vitro system will be tested in a mouse model for BC.

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