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WIREs Nanomed Nanobiotechnol
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Nanoparticle therapeutics: a personal perspective

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Abstract Nanotechnology offers many potential benefits to cancer research through passive and active targeting, increased solubility/bioavailablility, and novel therapies. However, preclinical characterization of nanoparticles is complicated by the variety of materials, their unique surface properties, reactivity, and the task of tracking the individual components of multicomponent, multifunctional nanoparticle therapeutics in in vivo studies. There are also regulatory considerations and scale‐up challenges that must be addressed. Despite these hurdles, cancer research has seen appreciable improvements in efficacy and quite a decrease in the toxicity of chemotherapeutics because of ‘nanotech’ formulations, and several engineered nanoparticle clinical trials are well underway. This article reviews some of the challenges and benefits of nanomedicine for cancer therapeutics and diagnostics. © 2009 John Wiley & Sons, Inc. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies

Hypothetical mechanism by which a PEG coating protects a nanoparticle from recognition by the immune system The left panel shows that the PEG coating prevents the transient interaction and binding of antibodies with proteins on the nanoparticle surface. The right panel shows that the same PEG coating does not interfere with recognition by the cellular receptors.

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The physicochemical characteristics of a nanoparticle influence biocompatibility Here we qualitatively show trends in relationships between the independent variables of particle size (neglecting contributions from attached coatings and biologics), particle zeta potential (surface charge), and solubility with the dependent variable of biocompatibility—which includes the route of uptake and clearance (shown in green), cytotoxicity (red), and RES recognition (blue).

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Nanoparticles interfere with the LAL test for endotoxin contamination All samples shown here were spiked with a known amount (0.4 EU/mL) of UPS grade endotoxin standard. The quality control sample (blue) and the dendrimer sample (yellow) yield signals very close to the theoretical value, and fall within USP limits of ± 50%. Quantification of endotoxin in the gold nanoparticle (green) sample is inhibited—the test result is below the acceptable limits, yielding a false‐negative endotoxin result. Quantification of the endotoxin in the polymer nanoparticles (burgundy) is enhanced—the test result is above the acceptable limit.

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