The use of quantum dots (QDs) in biomedical research has grown tremendously, yet successful examples of clinical applications are absent due to many clinical concerns. Here, we report on a new type of stable and biocompatible dendron-coated InP/ZnS core/shell QDs as a clinically translatable nanoprobe for molecular imaging applications. The QDs (QD710-Dendron) were demonstrated to hold several significant features: near-infrared (NIR) emission, high stability in biological media, suitable size with possible renal clearance and ability of extravasation. More importantly, a pilot mouse toxicity study confirmed that QD710-Dendron lacks significant toxicity at the doses tested. The acute tumor uptake of QD710-Dendron resulted in good contrast from the surrounding non-tumorous tissues, indicating the possibility of passive targeting of the QDs. The highly specific targeting of QD710-Dendron-RGD2 to integrin αvβ3–positive tumor cells resulted in high tumor uptake and long retention of the nanoprobe at tumor sites. In summary, QD710-Dendron and RGD modified nanoparticles demonstrate small size, high stability, biocompatibility, favorable in vivo pharmacokinetics, and successful tumor imaging properties. These features satisfy the requirements for clinical translation and should promote efforts to further investigate the possibility of using QD710-Dendron based nanoprobes in the clinical setting in the near future.
We report thermodynamic data for the chemical denaturation of iso-1-cytochromes c from Saccharomyces cerevisiae having amino acid substitutions R38A, N52I, and F82S in all possible combinations. The guanidine hydrochloride denaturation of isolated proteins was monitored by fluorescence measurements. The redox potentials, Eo', for both the folded and unfolded conformations have been measured. Free energy changes of chemical unfolding together with direct electrochemical measurement of the free energy changes of reduction for both the native and unfolded proteins yield a complete thermodynamic cycle, which includes four states of cytochrome c: oxidized folded, oxidized unfolded, reduced folded, and reduced unfolded. Completed cycles illustrate that the stability of cytochrome c to denaturing conditions is different for each amino acid substitution by an amount that depends on the heme oxidation state. Thus, the differential protein stability cannot be interpreted simply in terms of a hydrophobic effect, without also considering coupled Coulombic effects.
A novel precision-assembly methodology is described on the basis of the controlled, simultaneous assembly (CSA) of a core nanoparticle substrate and polyelectrolyte solutions. The method is capable of assembly rates at least as fast as 10(16) core particles s(-1) L(-1) and affords concentrated suspensions of stable colloids with an adsorbed polyelectrolyte. The resulting dispersions are highly homogeneous, have a low viscosity and narrow particle-size distribution, and are stable colloids, even at solid concentrations of at least 33 wt %. The adsorption isotherm and the saturation adsorption for polyethylenimine (PEI) assemblies onto a 15 nm silica colloid have been evaluated with 1H NMR spectroscopy. The saturation adsorption is highly dependent upon the pH at assembly and is given by the equation PEIa (micromol m(-2)) = 1.73pH - 1.89, R2 = 0.986, where micromoles refers to the concentration of the EI monomer. The saturation concentration increases from 6.8 micromol m(-2) at pH 5.0 to 13.7 micromol m(-2) at pH 9.0. The adsorbed polyelectrolyte may be cross-linked and thereby permanently fixed to the colloid surface to prepare nanoparticle-polyelectrolyte colloidal assemblies having enhanced colloid stability, high homogeneity, and a high fraction (>80%) of permanently adsorbed polyelectrolyte. These assemblies are stable at physiological pH and ionic strength and may represent ideal substrates for bioconjugation and, ultimately, the design of nanocarriers for in vivo applications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.