Selective Uptake Into Drug Resistant Mammalian Cancer by Cell Penetrating Peptide-Mediated Delivery.

Research over the past decade has identified several of the key limiting features of multidrug resistance (MDR) in cancer therapy applications, such as evolving glycoprotein receptors at the surface of the cell that limit therapeutic uptake, metabolic changes that lead to protection from multidrug resistant mediators which enhance degradation or efflux of therapeutics, and difficulty ensuring retention of intact and functional drugs once endocytosed. Nanoparticles have been demonstrated to be effective delivery vehicles for a plethora of therapeutic agents, and in the case of nucleic acid based agents, they provide protective advantages. Functionalizing cell penetrating peptides, also known as protein transduction domains, onto the surface of fluorescent quantum dots creates a labeled delivery package to investigate the nuances and difficulties of drug transport in MDR cancer cells for potential future clinical applications of diverse nanoparticle-based therapeutic delivery strategies. In this study, eight distinct cell penetrating peptides were used (CAAKA, HSV1-VP22, HIV-TAT, HIV-gp41, Ku-70, hCT(9-32), integrin-ß3, and K-FGF) to examine the different cellular uptake profiles in cancer versus drug resistant melanoma (A375 & A375-R), mesothelioma (MSTO & MSTO-R), and glioma (rat 9L and 9L-R, and human U87 & LN18) cell lines. The results of this study demonstrate that cell penetrating peptide uptake varies with drug resistance status and cell type, likely due to changes in cell surface markers. This study provides insight into developing functional nanoplatform delivery systems in drug resistant cancer models.

Ostwald's Rule of Stages and its role in CdSe quantum dot crystallization.

A century ago Ostwald described the "Rule of Stages" after deducing that crystal formation must occur through a series of intermediate crystallographic phases prior to formation of the final thermodynamically stable structure. Direct evidence of the Rule of Stages is lacking, and the theory has not been implemented to allow isolation of a selected structural phase. Here we report the role of Ostwald's Rule of Stages in the growth of CdSe quantum dots (QDs) from molecular precursors in the presence of hexadecylamine. It is observed that, by controlling the rate of growth through the reaction stoichiometry and therefore the probability of ion-packing errors in the growing QD, the initially formed zinc blende (ZB) critical nuclei representing the kinetic phase can be maintained at sizes >14 nm in diameter without phase transformation to the thermodynamic wurtzite (WZ) structure. An intermediate pseudo-ZB structure is observed to appear at intermediate reaction conditions, as predicted by Ostwald. The ZB and pseudo-ZB structures convert to the WZ lattice above a critical melting temperature. This study validates Ostwald's Rule of Stages and provides a phase diagram for growth of CdSe QDs exhibiting a specific crystallographic motif.

Ligand-passivated Eu:Y2O3 nanocrystals as a phosphor for white light emitting diodes.

Eu(III)-doped Y(2)O(3) nanocrystals are prepared by microwave synthetic methods as spherical 6.4 ± 1.5 nm nanocrystals with a cubic crystal structure. The surface of the nanocrystal is passivated by acetylacetonate (acac) and HDA on the Y exposed facet of the nanocrystal. The presence of acac on the nanocrystal surface gives rise to a strong S(0) → S(1) (π → π*, acac) and acac → Ln(3+) ligand to metal charge transfer (LMCT) transitions at 270 and 370 nm, respectively, in the Eu:Y(2)O(3) nanocrystal. Excitation into the S(0) → S(1) (π → π*) or acac → Ln(3+) LMCT transition leads to the production of white light emission arising from efficient intramolecular energy transfer to the Y(2)O(3) oxygen vacancies and the Eu(III) Judd-Ofelt f-f transitions. The acac passivant is thermally stable below 400 °C, and its presence is evidenced by UV-vis absorption, FT-IR, and NMR measurements. The presence of the low-lying acac levels allows UV LED pumping of the solid phosphor, leading to high quantum efficiency (∼19%) when pumped at 370 nm, high-quality white light color rendering (CIE coordinates 0.33 and 0.35), a high scotopic-to-photopic ratio (S/P = 2.21), and thermal stability. In a LED lighting package luminosities of 100 lm W(-1) were obtained, which are competitive with current commercial lighting technology. The use of the passivant to funnel energy to the lanthanide emitter via a molecular antenna effect represents a new paradigm for designing phosphors for LED-pumped white light.