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Transporter-mediated Targeted Drug Delivery

Endogenous solute carriers (SLCs) and ATP-binding cassette (ABC) proteins transport essential substrates, such as nutrients, hormones, neurotransmitters, metabolites, and drugs across the cell membranes and therefore, have a crucial role in substances’ distribution and disposition in the body. These transporters can also be utilized to enhance drug delivery and target drugs to specific organs of cells. Moreover, if transporter function or expression can be modulated in specific cells, the drug efficacy and safety could be greatly improved.

Our research group is developing novel transporter-utilizing (pro)drugs to:

1. Improve the drug delivery across the blood-brain barrier (BBB) and selectively into different cell types (neurons, astrocytes or microglia) within brain (intra-brain targeting)

    •  Explore if dual targeting of LAT1-utilizing compounds into the brain and simultaneously into the pancreas (brain-pancreas axis) can have beneficial effects on the treatment of neurodegenerative diseases

2. Target chemotherapeutics (prodrugs or drug analogues) selectively into the cancer cells

3. Inhibit specific transporters (influx or efflux) to block nutrient delivery into the cancer cell or drug efflux out of the cancer cells (chemoresistance) to increase antiproliferative effects

4. Modulate nutrient uptake (e.g. amino acids) or toxin uptake into the brain that can affect the progression of neurological diseases

5. Down-regulate transporter expression selectively in cancer cells or up-regulated transporter expression in target organs, such as brain or pancreas