Quantum dots protect against MPP＋-induced neurotoxicity in a cell model of Parkinson＇s disease through autophagy induction

Autophagy is a basic cellular process that decomposes damaged organelles and aberrant proteins. Dysregulation of autophagy is implicated in pathogenesis of neurodegenerative disorders, including Parkinson's disease(PD). Pharmacological compounds that stimulate autophagy can provide neuroprotection in models of PD. Nanoparticles have emerged as regulators of autophagy and have been tested in adjuvant therapy for diseases. In this present study, we explore the effects of quantum dots(QDs) that can induce autophagy in a cellular model of Parkinson's disease. Cd Te/Cd S/Zn S QDs protect differentiated rat pheochromocytoma PC12 cells from MPP+-induced cell damage, including reduced viability, apoptosis and accumulation of α-Synuclein, a characteristic protein of PD. The protective function of QDs is autophagy-dependent. In addition, we investigate the interaction between quantum dots and autophagic pathways and identify beclin1 as an essential factor for QDs-induced autophagy. Our results reveal new promise of QDs in the theranostic of neurodegenerative diseases.

Deciphering active biocompatibility of iron oxide nanoparticles from their intrinsic antagonism

Magnetite nanoparticles （Fe3O4 NPs） are a well proven biocompatible nanomaterial, which hold great promise in various biomedical applications. Interestingly, unlike conventional biocompatible materials （e.g., polyethylene glycol （PEG）） that are chemically and biologically inert in nature, Fe3O4 NPs are known to be catalytically active and exhibit prominent physiological effects. Herein, we report an ＂active＂, dynamic equilibrium mechanism for maintaining the cellular amenity of Fe3O4 NPs. We examined the effects of two types of iron oxide （magnetite and hematite） NPs in rat pheochromocytoma （PC12） cells and found that both induced stress responses. However, only Fe2O3 NPs caused significant programmed cell death; whereas Fe3O4 NPs are amenable to cells. We found that intrinsic catalase-like activity of Fe3O4 NPs antagonized the accumulation of toxic reactive oxygen species （ROS） induced by themselves, and thereby modulated the extent of cellular oxidative stress, autophagic activity, and programmed cell death. In line with this observation, we effectively reversed severe autophagy and cell death caused by Fe2O3 NPs via co-treatment with natural catalase. This study not only deciphers the distinct intrinsic antagonism of Fe3O4 NPs, but opens new routes to designing biocompatible theranostic nanoparticles with novel mechanisms.

Recognizing single phospholipid vesicle collisions on carbon fiber nanoelectrode

We recognize the stochastic collisions of dopamine contained phospholipid vesicle on carbon fiber nanoelectrode, extending the observation of discrete collision events on nanoelectrode to biologically relevant analytes. To decrease noise interference to the technique, the dimensions of nanoelectrode was systematically investigated and optimized. Scanning electron microscopy(SEM) further supported the comparable sizes of nanoelectrode and vesicles(~100 nm in diameter). Vesicles collision and rupture on the surface of nanoelectrode led to the dopamine release from vesicles, which could be electrochemically oxidized to dopamine-o-quinone and detected via voltammetry. The comparable size of the nanoelectrode with vesicles and fast voltammetry allowed differentiation of single collision events from the current magnitudes and peak widths in the electrochemical collision experiments, which shows the efficacy of the method to characterize vesicle samples. This work provides a foundation upon which quantitative sensor technology might be built for the detection of dopamine contained vesicles with high spatial and temporal resolution.

Phase transferring luminescent gold nanoclusters via single-stranded DNA

Atomically precise gold nanoclusters(Au NCs) are an emerging class of quantum-sized nanomaterials with discrete electronic energy levels, which has led to a range of attractive electronic and optical applications. Nevertheless, the lack of general methods to transfer Au NCs protected with hydrophobic ligands to an aqueous solution hampers their use in physiological settings. Here,we developed a single-stranded DNA-based approach that could transfer ~90% hydrophobic Au NCs into an aqueous solution.We experimentally and theoretically established that multivalent electrostatic and hydrophobic interactions between DNA strands and the hydrophobic ligand layer on Au NCs resulted in monodispersed DNA-coated Au NCs with high physical integrity in an aqueous solution. The fluorescence quantum yield of Au NCs was increased by ~13 fold, and surface-constrained DNA retained the specific recognition ability for biosensing. We further demonstrated the versatility of this phase-transfer approach, which thus holds great potential to advance biological and medical applications of Au NCs.

Facile Synthesis of 7-epi-Taxane and Its Derivatives and Preliminary Evaluation of Anticancer Activity

7-epi-Taxane has been achieved efficiently in gram scale from natural taxane via inversion of the 7-hydroxyl group simply using Ag20 as catalyst and DMF as solvent. The catalyst could he quantitatively recovered by filtra- tion without loss of catalytic activity. This condition is also applicable to the direct epimerization of taxane derivatives （e.g., docetaxel and paclitaxel） to 7-epi-taxane derivatives （e.g., 7-epi-docetaxel and 7-epi-paclitaxel）. Furthermore, 33 ester derivatives of 7-epi-taxane with different amino acid moieties at the position of C-13 were successfully synthesized via esterification without protecting C-7-OH. Bioassay results revealed that compounds 13 and 18 have good selectivity against prostatic cancer cell line DU145, with ICs0 value as low as 15.9 nmol/L for 18.