Mentor  Pharmaceutical Consulting


 
 
 

Cancer Targeting with Vitamins

Rapid cell growth and division, such as is seen in the growth of aggressive tumours requires increased uptake of several essential vitamins. Studies have shown that many cancer cell lines over-express proteins involved in the uptake of folate, vitamin B12 and/or biotin.

Vitamin B12 targeting to cancer cells

Many rapidly dividing cells, such as cancers of the breast, prostate, some leukaemias, and some kidney cell lines, actively accumulate vitamin B12. Vitamin B12 exists within the cell as two co-enzymes, methylcobalamin, which is involved in one carbon synthesis, essential for DNA synthesis, and adenosylcobalamin, which is involved in mitochondrial energy production within these highly metabolically active cells. Tumours showing enhanced uptake of vitamin B12 are known to synthesize both vitamin B12 binding proteins, and the binding protein receptors. Vitamin B12 has been found to be suitable for imaging these cancers in humans and also as a targeting agent for enhanced specificity of cytotoxins and polymer-bound cytotoxins.

Biotin targeting to cancer cells

Biotin is an essential vitamin, which is involved in cell growth, fatty acid metabolism and energy production within the cell. Recently, it has also been shown that biotin is required for biotinylation of histones. Receptors involved in the uptake of biotin have been found to be over-expressed on cancers of the breast, ovary, kidney, liver, prostate, and some lung cell lines. Biotin has been found to be suitable for imaging these cancers in humans and also as a targeting agent for enhanced specificity of cytotoxins and polymer-bound cytotoxins. Recent evidence suggests that uptake of biotin by these cells requires the synthesis of both a biotin binding protein (most likely biotinidase, which is then secreted), and a biotin binding protein receptor (which is expressed on the cell surface).

Biotin-targeted fluorescent polymers have been shown to greatly enhance the detection of small cancer masses and metastases.

Nuclear staining of Small Intestine and tumour metastases

Biotin-targeting
to
 tumour metastases

Dual Staining -
Nucleus (Blue)
Metastases (Red)

Biotin targeted Rhodamine-HPMA (red) successfully identifies micro-metastases located adjacent to normal small intestinal tissue.

Vitamin-targeted delivery systems have been shown to enhance cancer imaging and to increase the effectiveness and selectivity of several cytotoxins

Mentor can provide expertise in the design, synthesis and scale-up of targeted imaging agents and therapeutics for cancer therapy.

Mentor can provide expertise in the identification of potential serum markers for cancer detection.