title: Opportunities for near-infrared thermal ablation of colorectal metastases by guanylyl cyclase C-targeted gold nanoshells.
abstract: Colorectal cancer is the third most common malignancy and the second most common cause of cancer-related mortality worldwide. While surgery remains the mainstay of therapy, approximately 50% of patients who undergo resection develop parenchymal metastatic disease. Unfortunately, current therapeutic regimens offer little improvement to the survival of patients with parenchymal metastases in the liver and lung. In that context, there is a significant unrealized opportunity at the intersection of engineering and biology for the development of novel targeted therapeutic approaches to colorectal cancer metastases. This opportunity exploits the discovery that an intestinal receptor, guanylyl cyclase C, which mediates diarrhea induced by bacterial heat-stable enterotoxins (STs), is over-expressed by metastatic colorectal tumors only. Moreover, it leverages recent advances in the fabrication of metal nanoshells with defined thicknesses absorb near-infrared (NIR) light, resulting in resonance and transfer of thermal energies of more than 40 degrees C. Thus, the conjugation of ST to gold nanoshells, which can undergo resonance excitation by NIR light and emit heat, represents a previously unrecognized approach for the targeted therapy of parenchymal colorectal cancer metastases, specifically to the liver and lung. This article discusses the potential of ST-targeted nanoshells for NIR thermal ablation of metastatic colorectal tumors and highlights the significant challenges and solutions linked to the translation of this emerging technology to patient care.
authors.affiliation: Thomas Jefferson University, Jefferson Medical College, Department of Pharmacology & Experimental Therapeutics, Philadelphia, PA 19107, USA. scott.waldman@jefferson.edu
authors.forename: Scott A
authors.initials: SA
authors.lastname: Waldman
authors.forename: Paolo
authors.initials: P
authors.lastname: Fortina
authors.forename: Saul
authors.initials: S
authors.lastname: Surrey
authors.forename: Terry
authors.initials: T
authors.lastname: Hyslop
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Kricka
authors.forename: David J
authors.initials: DJ
authors.lastname: Graves
mesh_terms: D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D006046:Gold; D006162:Guanylate Cyclase; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007259:Infrared Rays; D053768:Metal Nanoparticles; D009362:Neoplasm Metastasis; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide
chemical_list: D014408:Biomarkers, Tumor; D018000:Receptors, Peptide; D006046:Gold; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled