Gold nanoparticles (AuNPs) are attractive photothermal agents for cancer therapy because they show efficient local heating upon excitation of surface plasmon oscillations. The strong absorption, efficient heat conversion, high photostability, inherent low toxicity and well-defined surface chemistry of AuNPs contribute to the growing interest in their photothermal therapy (PTT) applications. The facile tunability of gold nanostructures enables engineering of AuNPs for superior near-infrared photothermal efficacy and target selectivity, which guarantee efficient and deep tissue-penetrating PTT with mitigated concerns regarding side effects by nonspecific distributions. This article discusses the current research findings with representative near-infrared-active AuNPs, which include nanoshell, nanorod, nanocage, nanostar, nanopopcorn and nanoparticle assembly systems. AuNPs successfully demonstrate potential for use in PTT, but several hurdles to clinical applications remain, including long-term toxicity and a need for sophisticated control over biodistribution and clearance. Future research directions are discussed, especially regarding the clinical translation of AuNP photosensitizers.
Gold nanoparticles (AuNPs) have been extensively studied for photothermal cancer therapy because AuNPs can generate heat upon near-infrared irradiation. However, improving their tumor-targeting efficiency and optimizing the nanoparticle size for maximizing the photothermal effect remain challenging. We demonstrate that mesenchymal stem cells (MSCs) can aggregate pH-sensitive gold nanoparticles (PSAuNPs) in mildly acidic endosomes, target tumors, and be used for photothermal therapy. These aggregated structures had a higher cellular retention in comparison to pH-insensitive, control AuNPs (cAuNPs), which is important for the cell-based delivery process. PSAuNP-laden MSCs (MSC-PSAuNPs) injected intravenously to tumor-bearing mice show a 37-fold higher tumor-targeting efficiency (5.6% of the injected dose) and 8.3 °C higher heat generation compared to injections of cAuNPs after irradiation, which results in a significantly enhanced anticancer effect.
We report on measurements of electron transport for the fractional quantum Hall effect (FQHE) at filling factors v= -, and -,, in magnetic fields B, tilted by angles 0 with respect to the normal to the sample plane. Our device was prepared at an electron density of only 2.4X 10' cm, but still exhibited a well-developed FQHE at v= -, ' and -', . This exceptionally low density allowed us to access very low total fields, where the spin is less likely to be completely polarized. For many tilt angles, we obtained gap energies 6 from the temperature dependence of the diagonal conductivity on the FQHE minima. For both 3 and -, ', plots of 6 versus B, exhibit minima that are accompanied in transport by splitting of the FQHE. For -the minimum in h(B, ) is sharp and deep, with 6 reduced by 70%. With B, well above its value at the minimum, h(B, ) for v= -, is linear, with slope =gp& for GaAs, indicating an increase in the two-dimensional electron-system Zeeman energy on excitation. We present a detailed survey of the evolution of the splitting of the FQHE with angle, and find that local p""minima that are shifted up to 6% upfield of v= 3t at 8=23' evolve continuously into an unsplit FQHE at v= t3 at 8=0'. The split and shifted FQHE's that we observe are interpreted as effects of phase separation associated with groundstate spin transitions.
A challenge in using plasmonic nanostructure-drug conjugates for thermo-chemo combination cancer therapy lies in the huge size discrepancy; the size difference can critically differentiate their biodistributions and hamper the synergistic effect. Properly tuning the plasmonic wavelength for photothermal therapy typically results in the nanostructure size reaching ∼100 nm. We report a new combination cancer therapy platform that consists of relatively small 10 nm pH-responsive spherical gold nanoparticles and conjugated doxorubicins. They are designed to form aggregates in mild acidic environment such as in a tumor. The aggregates serve as a photothermal agent that can selectively exploit external light by their collective plasmon modes. Simultaneously, the conjugated doxorubicins are released. The spatiotemporal concertion is confirmed at the subcellular, cellular, and organ levels. Both agents colocalize in the cell nuclei. The conjugates accumulate in cancer cells by the rapid phagocytic actions and effective blockage of exocytosis by the increased aggregate size. They also effectively accumulate in tumors up to 17 times over the control because of the enhanced permeation and retention. The conjugates exhibit a synergistic effect enhanced by nearly an order of magnitude in cellular level. The synergistic effect is demonstrated by the remarkable reductions in both the therapeutically effective drug dosage and the photothermal laser threshold. Using an animal model, effective tumor growth suppression is demonstrated. The conjugates induce apoptosis to tumors without any noticeable damage to other organs. The synergistic effect in vivo is confirmed by qRT-PCR analysis over the thermal stress and drug-induced growth arrest.
We report magnetotransport measurements in a weakly coupled double-layer electron system realized in a wide quantum well. This system has the unique property that the distance and the coupling between the layers can be changed continuously by varying the electron density in the well. We observe the absence of quantum Hall states at odd filling factors. Our results complement earlier experimental work and are consistent with a recent theoretical model proposed for the magnetic-field-driven destruction of the quantum Hall effect in double quantum wells.The two-dimensional electron system (2DES) has provided the means for the observation of many new physical phenomena, such as the integral ' and fractional quantum Hall effects (IQHE and FQHE). Recently, there is much interest in the fabrication and physics of structures which contain two or more layers of electrons in close proximity so that the interlayer Coulomb interactions are strong. ' Theoretically, the possibility of new collective states such as the FQHE at even-denominator Landaulevel fillings (v), or Wigner crystallization in such multilayer structures has been proposed.There has also been some experimental work in these systems. The observation of the IQHE in multilayer systems with significant interlayer tunneling has been reported. ' Boebinger et al. recently studied the IQHE in strongly coupled, high-quality double quantum wells (DQW) in which the symmetric to antisymmetric energy gap (AsAs) is expected to give rise to the IQHE at odd v. They observed a remarkable effect, namely the absence of certain IQHE states at low-odd v for sufficiently small AsAs and large interlayer distance (d). The origin of this phenomenon is not clear yet although recent calculations relate it to the Coulomb-driven destruction of hsAs in a strong magnetic field. ' According to these calculations, if the magnetic field (8) is sufficiently strong, hsAs collapses and the DQW system makes a transition to a different ground state with weak interwell, but strong intrawell correlations.In this Rapid Communication, we report magnetotransport measurements in a novel high-quality double-layer system realized in a wide, single, GaAs quantum well (Fig. 1). The idea is that when electrons are introduced in a wide quantum well, the electrostatic repulsion between the electrons forces them into a stable configuration in which two 2DES's are formed at the well's sidewalls. A major advantage of this system over a conventional DQW is the minimization of alloy scattering since the barrier between the two 2DES's is GaAs rather than Al Gal -"-As. Also, both hsAs and d can be changed by varying the electron density (n, ) in the well (Figs. 1 and 2). Our study of this system in a regime~here the two 2DES's are weakly coupled reveals the absence of IQHE states at odd v. Our data can be qualitatively explained by the theories proposed by MacDonald, Platzman, and Boebinger and Brey. 0.3-I (a) empty 0.2------electron distribution Ec 0-I I I~I 0 3 -(b) n, = 5.6x10 cm 02-o 0.1
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