The Effect of Nanoparticle Size on Cellular Binding Probability

Nanoparticle-based contrast agents are expected to play a major role in the future of molecular imaging due to their many advantages over the conventional contrast agents. These advantages include prolonged blood circulation time, controlled biological clearance pathways, and specific molecular targeting capabilities. Recent studies have provided strong evidence that molecularly targeted nanoparticles can home selectively onto tumors and thereby increase the local accumulation of nanoparticles in tumor sites. However, there are almost no reports regarding the number of nanoparticles that bind per cell, which is a key factor that determines the diagnostic efficiency and sensitivity of the overall molecular imaging techniques. Hence, in this research we have quantitatively investigated the effect of the size of the nanoparticle on its binding probability and on the total amount of material that can selectively target tumors, at a single cell level. We found that 90？nm GNPs is the optimal size for cell targeting in terms of maximal Au mass and surface area per single cancer cell. This finding should accelerate the development of general design principles for the optimal nanoparticle to be used as a targeted imaging contrast agent. 1. Introduction Imaging plays a critical role in overall cancer management; in diagnostics, staging, radiation planning, and evaluation of treatment efficiency. Conventional imaging technologies for cancer detection such as CT, MRI, and ultrasound can be categorized as structural imaging modalities. They are able to identify anatomical patterns and to provide basic information regarding tumor location, size, and spread based on endogenous contrast. However, these imaging modalities are not efficient in detecting tumors and metastases that are smaller than 0.5？cm [1], and they can barely distinguish between benign and cancerous tumors. Molecular imaging is an emerging field that integrates molecular biology, chemistry, physics, and medicine in order to gain understanding regarding biological processes and to identify diseases based on molecular markers, which appear before the clinical presentation of the disease. Recently, much research has focused on the development of targeted nanoparticles for use as contrast agents for molecular imaging. These include superparamagnetic nanoparticles for MRI [2–6], quantum dots for optical imaging [7–9], and gold nanoparticles (GNPs) for optical imaging [10, 11] and CT [12–14]. GNPs are a class of contrast agents with unique optical properties. They are well known for their strong interactions