Designing nanoconjugates to effectively target pancreatic cancer cells in vitro and in vivo

• Published in: PloS one Vol. 6; no. 6; p. e20347
• Main Authors: Khan, Jameel Ahmad, Kudgus, Rachel A, Szabolcs, Annamaria, Dutta, Shamit, Wang, Enfeng, Cao, Sheng, Curran, Geoffry L, Shah, Vijay, Curley, Steven, Mukhopadhyay, Debabrata, Robertson, J David, Bhattacharya, Resham, Mukherjee, Priyabrata
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.06.2011; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Biochemistry; Biological products; Biomedical engineering; Cancer; Cancer cells; Cancer research; Cancer therapies; Cancer treatment; Capillaries; Care and treatment; Cell Line, Tumor; Cetuximab; Computed tomography; Contrast agents; Design; Design parameters; Drug delivery; Drug delivery systems; Epidermal growth factor; Epidermal growth factor receptors; Epidermal growth factors; Fever; Gold; Gold - chemistry; Growth factors; Health aspects; Humans; Hyperthermia; Immunoglobulins; Kinases; Leukemia; Ligands; Materials Science; Mathematical models; Medical imaging; Medical research; Medicine; Metal Nanoparticles - chemistry; Mice; Mice, Nude; Microscopy, Electron, Transmission; Molecular biology; Monoclonal antibodies; Nanoconjugates - chemistry; Nanomaterials; Nanoparticles; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Particle size; Phosphorylation; Physiology; Radio frequency; Surface area; Targeted cancer therapy; Tumor cells; Tumors; Xenograft Model Antitumor Assays; Minnesota; Missouri
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0020347

Pancreatic cancer is the fourth leading cause of cancer related deaths in America. Monoclonal antibodies are a viable treatment option for inhibiting cancer growth. Tumor specific drug delivery could be achieved utilizing these monoclonal antibodies as targeting agents. This type of designer therapeutic is evolving and with the use of gold nanoparticles it is a promising approach to selectively deliver chemotherapeutics to malignant cells. Gold nanoparticles (GNPs) are showing extreme promise in current medicinal research. GNPs have been shown to non-invasively kill tumor cells by hyperthermia using radiofrequency. They have also been implemented as early detection agents due to their unique X-ray contrast properties; success was revealed with clear delineation of blood capillaries in a preclinical model by CT (computer tomography). The fundamental parameters for intelligent design of nanoconjugates are on the forefront. The goal of this study is to define the necessary design parameters to successfully target pancreatic cancer cells. The nanoconjugates described in this study were characterized with various physico-chemical techniques. We demonstrate that the number of cetuximab molecules (targeting agent) on a GNP, the hydrodynamic size of the nanoconjugates, available reactive surface area and the ability of the nanoconjugates to sequester EGFR (epidermal growth factor receptor), all play critical roles in effectively targeting tumor cells in vitro and in vivo in an orthotopic model of pancreatic cancer. Our results suggest the specific targeting of tumor cells depends on a number of crucial components 1) targeting agent to nanoparticle ratio 2) availability of reactive surface area on the nanoparticle 3) ability of the nanoconjugate to bind the target and 4) hydrodynamic diameter of the nanoconjugate. We believe this study will help define the design parameters for formulating better strategies for specifically targeting tumors with nanoparticle conjugates.