Pharma Strategy Blog

Way back in November 2009 at the American Association of Cancer Research (AACR) Molecular Targets meeting in Boston, there was a fascinating poster on the early promise for nanotechnology as a new form of efficient drug delivery for cancer therapeutics (see the blog post here).

Fast forward 18 months and my attention was drawn to a new article published in Cancer Research about how nanotechnology has been used preclinically to deliver therapy for breast cancer into the cancer cells rather than to the cells.  This is a subtle, but important, difference.

For those of your wondering what nanotechnology is, my colleague Pieter Droppert reviewed some basics earlier this month in a blog post:

“Nanotechnology is the application of science and engineering to materials that are between 1 and 100 nanometers (nm) in size.”

He went on to put this in layman terms:

“1nm is one-billionth of a meter.   To put this in context, 1nm is one seven-thousandth of the width of a red blood cell or one eighty-thousandth of the width of a human hair.  These are unimaginably small materials that are engineered to operate at the molecular and atomic level.”

The approach in the latest preclinical research (see references below) is to take trastuzumab (Herceptin) and combine it with biodegradable polymers to form nanoconjugates that are small enough to enter cancer cells because they are more water soluble rather than attack the outside of the cells, thereby potentially reducing toxicities associated with the therapy.

The same group also tried this technique with brain cancer (see references below), allowing the nanocells to cross the usually impenetratable blood-brain barrier, which:

“resulted in a marked inhibition of tumor angiogenesis and growth.”

In the breast cancer research, the group compared the results of their polymer-trastuzumab conjugate with trastuzumab alone in mice:

“Our experiments confirmed that a proper design of the lead nanobiopolymer was possible for efficient blocking of HER2/neu-positive breast tumor growth through dual inhibition of HER2/neu and Akt phosphorylation, and as a result, promoting enhanced tumor cell apoptosis.

The nanobiopolymer’s unique combination of features resulted in highly specific drug accumulation in the tumor tissue and inside tumor cells.”

It will be most interesting to see if this idea is developed clinically in human trials and whether the results will be reproducible or not.

Significance of the findings:

The nanoconjugate concept has promise, not just in allowing a novel drug delivery system to cross impenetrable barriers, but also in reducing the toxicities associated with systemic targeted therapy.  Randomised clinical trials in patients with cancer are required to determine if there is viability in humans.

References:

Inoue, S., Ding, H., Portilla-Arias, J., Hu, J., Konda, B., Fujita, M., Espinoza, A., Suhane, S., Riley, M., Gates, M., Patil, R., Penichet, M., Ljubimov, A., Black, K., Holler, E., & Ljubimova, J. (2011). Polymalic Acid-Based Nanobiopolymer Provides Efficient Systemic Breast Cancer Treatment by Inhibiting both HER2/neu Receptor Synthesis and Activity Cancer Research, 71 (4), 1454-1464 DOI: 10.1158/0008-5472.CAN-10-3093

Ljubimova, J., Fujita, M., Ljubimov, A., Torchilin, V., Black, K., & Holler, E. (2008). Poly(malic acid) nanoconjugates containing various antibodies and oligonucleotides for multitargeting drug delivery Nanomedicine, 3 (2), 247-265 DOI: 10.2217/17435889.3.2.247

Ding, H., Inoue, S., Ljubimov, A., Patil, R., Portilla-Arias, J., Hu, J., Konda, B., Wawrowsky, K., Fujita, M., Karabalin, N., Sasaki, T., Black, K., Holler, E., & Ljubimova, J. (2010). Inhibition of brain tumor growth by intravenous poly( -L-malic acid) nanobioconjugate with pH-dependent drug release Proceedings of the National Academy of Sciences, 107 (42), 18143-18148 DOI: 10.1073/pnas.1003919107