• Vitamin B₁₂ is essential for DNA synthesis and therefore cell division
• Rapidly dividing cells need to synthesize DNA and therefore have a greater need for Vitamin B12
• Cell surface receptors are presumed to be up-regulated in rapidly dividing cells such as cancers
• Vitamin B12 is transported in the body by a large protein carrier called Transcoblamin II (TCII in the diagram above) which is recognized by a cell surface receptor. The complex is then internalized into the cell through a clathrin coated pit and further trafficked in the cell. 
• Once the bioconjugate reaches the lysozome it is designed to release the drug of interest.
• Based on this mechanism it is hoped that several advantages will be realized:

1. Since drug will not be released except after the bioconjugate enters the target cell then systemic toxicity should be reduced
2. Based on the B12 targeting drug should accumulate disproportionately in the target cells
3. Based on differential trafficking in the cell, as compared to free drug,  there may be a chance to avoid Multiple Drug Resistance (MDR) pumps and achieve broader applicability to a wider range of tumor types

Based on our initial animal studies we are achieving substantially lower toxicity and improved efficacy by using this approach. 

 

 

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