Nanoparticles and Prostate Cancer

Amarnath Mukherjee, PhD

Nanoparticles are small objects having a diameter in the nano-meter range (10-9 m) which behave as small individual particles. Over the last two decades, nanoparticles have made its impact in every area of science and technology. This is because they possess distinct properties (attributed to their small size and high surface to volume ratio) which can be explored for unique use. For example, iron-oxide based nanoparticles have been simultaneously used both in imaging (as MRI contrast agents) and therapy (through hyperthermia or drug delivery). [1] Amarnath Mukherjee, PhD, is a researcher in the Brady Urological Insitute at Johns Hopkins, who is studying the use of nanoparticle for potential cancer therapy/diagnosis with Shawn E. Lupold, PhD, and Co-Director of the Prostate Cancer Program at the Sidney Kimmel Cancer Center at Hopkins.

Prostate Specific Membrane Antigen (PSMA) is an established target for cancer therapeutic and imaging agents due to its high expression on the surface of prostate cancer cells and within the neovasculature of other solid tumors. Drs. Mukherjee and Lupold have developed a humanized anti-PSMA antibody conjugated silica-coated iron oxide nanoparticles for PSMA-specific cell binding – a iron oxide nanoparticle that can hone specifically to prostate cancer cells. [2] Customized assays utilizing iron spectral absorbance and Enzyme-Linked Immunoassay (ELISA) were developed to screen nanoparticle formulations for immunoreactivity and PSMA-targeting. Antibody and PSMA-specific targeting of the optimized nanoparticle was evaluated using an isogenic PSMA-positive and PSMA-negative cell line pair. These nanoparticles and the methods used to validate their function support the promise of targeted theranostic agents for future treatment of prostate and other cancers.

Although nanoparticles offer significant promise for new mode of diagnosis and therapy, they come with new challenges. For example, Iron oxide nanoparticles capable of generating localized heat are reshaping the concept of targeted and focal hyperthermia as a cancer therapy. Traditional hyperthermia (or energy ablation) uses energy sources to destroy a target lesion, usually localized with imaging like CT, MRI or ultrasound. However, nanoparticle-mediated hyperthermia is different than traditional hyperthermia in a few senses. First, nanoparticle-mediated hyperthermia has the ability to target microscopic foci of cancer not seen on traditional imaging. In addition, traditional hyperthermia often destroys tissues, both malignant and benign, within a “killzone” created by the energy source. Drs. Mukherjee and Lupold have studied and compared (using temperature sensitive secreted luciferase-based reporter gene system) thermal stress response, at the cellular level, to macroscopic and NP hyperthermia. [3] The results indicate that cells can detect mild heat stress from nanoparticles at temperatures too low to measurably alter the macroscopic temperature of the system – indicating that the target cells can be “cooked” without damaging nearby normal cells. The results also suggest that cells which were closer to the nanoscopic heat source experienced greater thermal stress. Further characterization of the nature of nanoparticle heating and its relationship to macroscopic hyperthermia is needed prior to moving nanoparticle research into human experiments and the clinic.

[1] N. Ahmed, H. Fessi, A. Elaissari, Drug discovery today 2012, 17, 928-934.
(http://www.ncbi.nlm.nih.gov/pubmed/22484464)
[2] A. Mukherjee, T. Darlington, R. Baldwin, et al ChemMedChem 2014.
(http://www.ncbi.nlm.nih.gov/pubmed/24591351)
[3] A. Mukherjee, M. Castanares, M. Hedayati, et al Nanomedicine (Lond) 2014.
(http://www.ncbi.nlm.nih.gov/pubmed/24547783)