Designing Nanoconjugates to Effectively Target Pancreatic Cancer Cells In Vitro and In Vivo

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

Parametric analysis of a shock absorber for motorcycle suspension

This study exposes a mathematical model developed to predict the restoring force produced by a mono-tube shock absorber. The model considers mainly the hydraulic oil flow through orifices and the deformation of the disks-valve on the piston. In both compression and rebound phases, an iterative process was set up in order to determine the restoring force. Simulating alternate excitations, an analysis was then performed for evaluating the influence of the following parameters: disks-valve thickness, orifices diameter, rod diameter and disks-valve pre-load for rebound. The results obtained in the simulation highlight that the variations of the pre-load and of the disks-valve thickness are more influential than the variations of the remaining two parameters

Gold nanoparticles surface plasmon field effects on the proton pump process of the bacteriorhodopsin photosynthesis

The rate of the proton pump of bacteriorhodopsin photosynthetic system is examined in the presence of a gold nanorod plasmon field. It is found that while the rate of the proton dissociation from the protonated Schiff base is not affected, the rate of its reprotonation increases. These results are qualitatively discussed in terms of several possible mechanisms. © 2009 American Chemical Society