Wenxin Li

The cytotoxicity of cadmium based, aqueous phase -Synthesized, quantum dots and its modulation by surface coating

In this report, we evaluated the cytotoxicity of a series of quantum dots (QDs) directly synthesized in aqueous phase, i.e., thiols-stabilized CdTe, CdTe/CdS core-shell structured and CdTe/CdS/ZnS core-shell-shell structured QDs, with a variety of cell lines including K562 and HEK293T. We have demonstrated that the CdTe QDs are highly toxic for cells due to the release of cadmium ions. Epitaxial growth of a CdS layer reduces the cytotoxicity of QDs to a small extent. However, the presence of a ZnS outlayer greatly improves the biocompatibility of QDs, with no observed cytotoxicity even at very high concentration and long-time exposure in cells. Our systematic investigation clearly shows that the cytotoxicity of QDs can be modulated through elaborate surface coatings and that the CdTe/CdS/ZnS core-shell-shell structured QDs directly synthesized in aqueous phase are highly promising biological fluorescent probes for cellular imaging.

The Biocompatibility of Nanodiamonds and Their Application in Drug Delivery Systems

Nanodiamonds (NDs), as a new member of the carbon nanoparticles family, have attracted more and more attention in biomedicine recently due to their excellent physical and chemical properties. This paper summarizes the main results from the in vitro and in vivo safety assessments of NDs and reports the application of NDs in the development of drug delivery systems. In view of the NDs characteristics of easy formation of a porous cluster structure in solution, an adsorption model for a variety of functional molecules on the ND clusters is proposed, which provides new ideas for developing a novel smart drug with various features such as sustained-release, targeting, and fluorescence imaging.

The cytotoxicity of CdTe quantum dots and the relative contributions from released cadmium ions and nanoparticle properties

A systematic study was carried out on the relationship between the cytotoxicity of quantum dots (QDs) and free cadmium ions using CdCl(2) solution with known amounts of Cd(2+) as the control. We found that the CdTe QDs were more cytotoxic than CdCl(2) solutions even when the intracellular Cd(2+) concentrations were identical in HEK293 cells treated with them, implying the cytotoxicity of CdTe QDs cannot attributed solely to the toxic effect of free Cd(2+). Moreover, we discovered that the cytotoxicity of QDs was based on the concentration of total QDs ingested by cells. Our data clearly showed that specific properties of nanoparticles have an obvious influence on their cytotoxicity.

Nanodiamonds as intracellular transporters of chemotherapeutic drug

To explore the application of nanodiamonds (NDs) as anticancer drug delivery vehicles, firstly we examined the toxicity of NDs to three kinds of mammalian cells. The studies indicated that serum proteins in cell culture medium had significant effect. When cells were exposed to NDs dispersed in complete cell culture medium, no cytotoxicity was detected. However, severe cell death was found after exposed to NDs dispersed in serum-free medium. Possible reasons for serum-dependent cytotoxicity were discussed and the potential influence of serum on the test of efficacy was pointed for anticancer drug delivery system based on NDs. Then adsorption of anticancer drug 10-hydroxycamptothecin (HCPT) by NDs was studied. Experiments indicated that diluted NaOH solution could promote the loading of HCPT on NDs. And a slow release of HCPT from the HCPT-ND complex was established in low pH media. Assessments of cell viability and imaging with transmission electron microscopy demonstrated a much higher efficacy of the HCPT-ND complex compared with HCPT alone. On the basis of adsorption feature of ND aggregates, new strategy for the design of targeting drug delivery systems of NDs was proposed.

Biodistribution and toxicity of nanodiamonds in mice after intratracheal instillation

Nanodiamonds (NDs) are receiving increasing attention in materials science and nanotechnology-based industries for a large variety of applications, including protein immobilization, biosensors, therapeutic molecule delivery, and bioimaging. However, limited information is known about their biokinetic behavior and toxicity in vivo. In this article, we investigated the biodistribution of NDs using radiotracer techniques and evaluated its acute toxicity in Kun Ming mice after intratracheal instillation. The biodistribution showed that, besides having the highest retention in the lung, NDs were distributed mainly in the spleen, liver, bone and heart. An analysis of histological morphology and biochemical parameters indicated that NDs could induce dose-dependent toxicity to the lung, liver, kidney and blood. This work provided fundamental data for understanding the biodistribution of NDs and will provide guidance for further study of their toxicity.

Polyhydroxylated fullerene derivative C60(OH)24 prevents mitochondrial dysfunction and oxidative damage in an MPP+-induced cellular model of Parkinson's disease

To find effective agents for Parkinsons disease (PD) prevention and therapy, we examined the protective effects of the polyhydroxylated fullerene derivative C60(OH)24 in a 1‐methyl‐4‐phenylpyridinium (MPP+)‐induced acute cellular PD model in human neuroblastoma cells and the free radical scavenging effects in this model with an electron spin resonance (ESR) spectrometer. Pretreatment with C60(OH)24 at concentrations greater than 20 μM showed significant protective effects on MPP+‐induced loss in cell viability, decreases in mitochondrial function (including mitochondrial membrane potential and activities of complex I and II), and increases in the levels of reactive oxygen species and oxidative damage to DNA and proteins. In addition, C60(OH)24 acts as a phase 2 enzyme inducer to protect cells from MPP+‐induced decreases in expression of nuclear factor‐E2‐related factor 2, expression and activity of γ‐glutamyl cysteine ligase and level of glutathione. The ESR study showed that C60(OH)24 is a powerful radical scavenger for superoxide, hydroxyl, and lipid radicals. These data suggest that C60(OH)24 is a mitochondrial protective antioxidant with direct radical scavenging activity and indirect antioxidant inducing activity.

Magnetically assisted DNA assays: high selectivity using conjugated polymers for amplified fluorescent transduction

We report a strategy for conjugated polymer (CP)-based optical DNA detection with improved selectivity. The high sensitivity of CP-based biosensors arises from light harvesting by the CP and the related amplified fluorescent signal transduction. We demonstrate that the use of magnetic microparticles significantly improves the selectivity of this class of DNA sensors. Compared with previously reported DNA sensors with CP amplification, this novel sensing strategy displays excellent discrimination against non-cognate DNA in the presence of a protein mixture or even human serum. We also demonstrate that the magnetically assisted DNA sensor can conveniently identify even a single-nucleotide mismatch in the target sequence.

Dependence of the cytotoxicity of multi-walled carbon nanotubes on the culture medium

This study examined the influence of multi-walled carbon nanotubes (MWNTs) on the growth of the unicellular protozoan Tetrahymena pyriformis. Contrary to the findings from most other investigations, our experiment indicated that MWNTs stimulated growth of the cells cultured in proteose peptone yeast extract medium (PPY). Atomic force microscopy images and thermogravimetric analysis showed the spontaneous formation of peptone-MWNT conjugates in the medium by noncovalent binding. Uptake of large amounts of the conjugates by Tetrahymena pyriformis was responsible for growth stimulation, evidenced by images with fluorescently labelled peptone. After the PPY medium was replaced by a filtrated pond water medium (FPW), however, inhibition of the growth of cells exposed to MWNTs occurred. Measurements of the level of malondialdehyde and superoxide dismutase activity demonstrated further that MWNTs might be either toxic or nontoxic, depending on the medium used to cultivate Tetrahymena pyriformis. The biological effects of the interaction of MWNTs with some composites in culture media would be helpful for understanding the mechanisms of the toxicity of carbon nanotubes to living systems.

The polyhydroxylated fullerene derivative C60(OH)24 protects mice from ionizing-radiation-induced immune and mitochondrial dysfunction

Although the protective effect of the polyhydroxylated fullerene derivative C(60)(OH)(n) against ionizing radiation is an area of much interest, the mechanisms relating to how polyhydroxylated fullerene derivatives improve mitochondrial dysfunction remain unknown. In order to find new and effective radioprotective agents, we synthesized a new polyhydroxylated fullerene molecule with 24 hydroxyl groups of known positions on C(60) and studied its protective effects in mice subjected to irradiation. Mice were pretreated with C(60)(OH)(24) for 2 weeks (daily, 40 mg/kg i. p.), then subjected to a lethal dose of whole body gamma-irradiation (from a (60)Co source). Survival was observed for 30 days after irradiation. Immune and mitochondrial dysfunction and oxidative damage were analyzed in mice with the same C(60)(OH)(24) pretreatment and irradiation except that the animals were euthanized at day 5 after the irradiation. It was found that 2-week C(60)(OH)(24) pretreatment effectively reduced whole body irradiation-induced mortality without apparent toxicity. C(60)(OH)(24) pretreatment also showed significant protective effects against ionizing-radiation-induced decreases in immune and mitochondrial function and antioxidant defense in the liver and spleen. These results suggest that the polyhydroxylated fullerene derivative C(60)(OH)(24) protects against ionizing-radiation-induced mortality, possibly by enhancing immune function, decreasing oxidative damage and improving mitochondrial function.

Comparative study on the acute pulmonary toxicity induced by 3 and 20 nm TiO2 primary particles in mice

The acute pulmonary toxicity induced by 3-nm TiO(2) primary particles was preliminary investigated after they were intratracheally instilled at doses of 0.4, 4 and 40mg/kg into lungs of mice. The biochemical parameters in bronchoalveolar lavage fluid (BALF) and pathological examination were used as endpoints to assess their pulmonary toxicity at 3-day postexposure. As such, the pulmonary toxicity assessment of 20-nm TiO(2) primary particles was performed using the same method. It was found that the 3-nm TiO(2) primary particles induced no pulmonary toxicity at dose of 0.4mg/kg, moderate toxicity at 4mg/kg and lung overload at 40mg/kg, and this kind of particles did not produce more pulmonary toxicity than the 20-nm ones at any instilled doses. As regards physicochemical characteristics of the two TiO(2) particles, their pH values in medium, other than particle size, surface area and aggregation, may play important role in affecting their pulmonary toxicity.