No abstract

Gold nanomaterials have received great interest for their use in cancer theranostic applications over the past two decades. Many gold nanoparticle-based drug delivery system designs rely on adsorbed ligands such as DNA or cleavable linkers to load therapeutic cargo. The heightened research interest was recently demonstrated in the simple design of nanoparticle-drug conjugates wherein drug molecules are directly adsorbed onto the as-synthesized nanoparticle surface. The potent chemotherapeutic, doxorubicin often serves as a model drug for gold nanoparticle-based delivery platforms; however, the specific interaction facilitating adsorption in this system remains understudied. Here, for the first time, we propose empirical and theoretical evidence suggestive of the main adsorption process where (1) hydrophobic forces drive doxorubicin towards the gold nanoparticle surface before (2) cation-π interactions and gold-carbonyl coordination between the drug molecule and the cations on AuNP surface facilitate DOX adsorption. In addition, biologically relevant compounds, such as serum albumin and glutathione, were shown to enhance desorption of loaded drug molecules from AuNP at physiologically relevant concentrations, providing insight into the drug release and in vivo stability of such drug conjugates.

A major challenge in designing cancer therapies is the induction of cancer cell apoptosis, although activation of intrinsic apoptotic pathways by targeting gold nanoparticles to mitochondria is promising. We report an in vitro procedure targeting mitochondria with conjugated gold nanoparticles and investigating effects on apoptosis induction in the human breast cancer cell line Jimt-1. Gold nanoparticles were conjugated to a variant of turbo green fluorescent protein (mitoTGFP) harbouring an amino-terminal mitochondrial localization signal. Au nanoparticle conjugates were further complexed with cationic maltotriose-modified poly(propylene imine) third generation dendrimers. Fluorescence and transmission electron microscopy revealed that Au nanoparticle conjugates were directed to mitochondria upon transfection, causing partial rupture of the outer mitochondrial membrane, triggering cell death. The ability to target Au nanoparticles into mitochondria of breast cancer cells and induce apoptosis reveals an alternative application of Au nanoparticles in photothermal therapy of cancer.

The toxicity of arsenic (As) species to Lemna gibba L. and the influence of PO(4) (3-) on As bioavailability and uptake were tested in batch culture. L. gibba were exposed to six test concentrations of NaHAsO(4). 7H(2)O and NaAsO(3), with 0, 0.0136, 13.6, and 40 mg L(-1) KH(2)PO(4). In batch culture As toxicity to L. gibba did not relate linearly to As concentration. The growth rate, related to frond number as recommended by OECD and ISO/DIN, was significantly inhibited in fronds exposed to 20-50 microg L(-1) As(III) compared with fronds exposed to As(V). The growth rate was stimulated when plants were exposed to 50-250 microg L(-1) of both As(III) and As(V). After exposure to 300-800 microg L(-1) growth inhibition was significantly higher for As(III) than for As(V), whereas above 800 microg L(-1) As(V) was inhibited the most. The bioaccumulation of As(III) and As(V) was significantly higher for P-deficient cultures (0.98 +/- 0.08 and 1.02 +/- 0.19 g kg(-1), respectively for 0.0136 mg L(-1) PO(4) (3-)) than for P-sufficient cultures (243 and 343 mg kg(-1) for 40 mg L(-1), respectively). Plants exposed to As(V) had uptake and accumulation values slightly higher than did plants exposed to As(III). No significant differences in bioaccumulation were found between plants exposed to a concentration of As(III) >1 mg L(-1) and those exposed to As(V) at the same concentration. This indicates a direct relationship to P content in the culture. Toxicity may result from the uptake of As(V) instead of PO(4) (3-) as a result of ion competition during uptake because of close thermodynamic properties, which may change the interaction among components in the media. The toxicity pattern is interpreted as a manifestation of changing speciation in the batch culture and of the oxidation of As(III) to As(V) in an oxygen-rich environment.