Quantitative estimation of gold nanoshell concentrations in whole blood using dynamic light scattering.

We demonstrate a new nondestructive optical assay to estimate submicron solid particle concentrations in whole blood. We use dynamic light scattering (DLS), commonly used to estimate nanoparticle characteristics such as size, surface charge, and degree of aggregation, to quantitatively estimate concentration and thereby estimate the actual delivered dose of intravenously injected nanoparticles and the longitudinal clearance rate. Triton X-100 is added to blood samples containing gold (Au) nanoshells to act as a quantitative scattering standard and blood lysing agent. The concentration of nanoshells was determined to be linearly proportional (R(2) = 0.998) to the relative light scattering attributed to nanoshells via DLS as compared with the Triton X-100 micelles in calibration samples. This relationship was found to remain valid (R(2) = 0.9) when estimating the concentration of circulating nanoshells in 15-muL blood samples taken from a murine tumor model as confirmed by neutron activation analysis. Au nanoshells are similar in size and shape to other types of nanoparticles delivered intravascularly in biomedical applications, and given the pervasiveness of DLS in nanoscale particle manufacturing, this simple technique should have wide applicability toward estimating the circulation time of other solid nanoparticles.

[1]  D. P. O'Neal,et al.  Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. , 2004, Cancer letters.

[2]  L. Brannon-Peppas,et al.  Nanoparticle and targeted systems for cancer therapy. , 2004, Advanced drug delivery reviews.

[3]  Glenn P. Goodrich,et al.  Scattering Spectra of Single Gold Nanoshells , 2004 .

[4]  Jun Fang,et al.  Vascular permeability enhancement in solid tumor: various factors, mechanisms involved and its implications. , 2003, International immunopharmacology.

[5]  Division on Earth Guide for the Care and Use of Laboratory Animals , 1996 .

[6]  Naomi J. Halas,et al.  Controlling the surface enhanced Raman effect via the nanoshell geometry , 2003 .

[7]  Emil Prodan,et al.  Electronic Structure and Optical Properties of Gold Nanoshells , 2003 .

[8]  W. Brown Dynamic light scattering : the method and some applications , 1993 .

[9]  M. Woodle,et al.  Controlling liposome blood clearance by surface-grafted polymers. , 1998, Advanced drug delivery reviews.

[10]  Naomi J. Halas,et al.  Nanoengineering of optical resonances , 1998 .

[11]  C. Cho,et al.  Polyethylene glycol (PEG) modified 99mTc-HMPAO-liposome for improving blood circulation and biodistribution: the effect of the extent of PEGylation. , 2005, Cancer biotherapy & radiopharmaceuticals.

[12]  J L West,et al.  A whole blood immunoassay using gold nanoshells. , 2003, Analytical chemistry.

[13]  R. Jain,et al.  Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[14]  S M Moghimi,et al.  Long-circulating and target-specific nanoparticles: theory to practice. , 2001, Pharmacological reviews.

[15]  J. D. Payne,et al.  Application of INAA to the build-up and clearance of gold nanoshells in clinical studies in mice , 2007 .

[16]  M. Dewhirst,et al.  Hyperthermia enables tumor-specific nanoparticle delivery: effect of particle size. , 2000, Cancer research.

[17]  B. Shoichet,et al.  High-throughput assays for promiscuous inhibitors , 2005, Nature chemical biology.

[18]  J. J. Freire,et al.  Dynamic Light Scattering from Mixtures of Two Polystyrene Samples in Dilute and Semidilute Solutions , 1996 .

[19]  Levine,et al.  One- and two-particle microrheology , 2000, Physical review letters.