Delivery of therapeutic or diagnostic agents across an intact blood–brain barrier (BBB) remains a major challenge. Here we demonstrate in a mouse model that magnetic nanoparticles (MNPs) can cross the normal BBB when subjected to an external magnetic field. Following a systemic administration, an applied external magnetic field mediates the ability of MNPs to permeate the BBB and accumulate in a perivascular zone of the brain parenchyma. Direct tracking and localization inside endothelial cells and in the perivascular extracellular matrix in vivo was established using fluorescent MNPs. These MNPs were inert and associated with low toxicity, using a non-invasive reporter for astrogliosis, biochemical and histological studies. Atomic force microscopy demonstrated that MNPs were internalized by endothelial cells, suggesting that trans-cellular trafficking may be a mechanism for the MNP crossing of the BBB observed. The silica-coated magnetic nanocapsules (SiMNCs) allow on-demand drug release via remote radio frequency (RF) magnetic field. Together, these results establish an effective strategy for regulating the biodistribution of MNPs in the brain through the application of an external magnetic field.

Nanocapsules containing intentionally trapped magnetic nanoparticles and defined anticancer drugs have been prepared to provide a powerful magnetic vector under moderate gradient magnetic fields. These nanocapsules can penetrate into the interior of tumors and allow a controlled on-off switchable release of the drug cargo via remote RF field. This smart drug delivery system is compact as all the components can be self-contained in 80-150 nm capsules. In vitro as well as in vivo results indicate that these nanocapsules can be enriched near the mouse breast tumor and are effective in reducing tumor cell growth.

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Loading or filling nanostructures with antibiotics can be one of the relevant approaches for obtaining a controlled drug release rate. Vertically aligned silicon nanowire (SiNW) arrays with 10-40 nm diameter wires having 1-3 microm in length obtained by the electroless etching (EE) technique are used in this study as novel nanostructures for mediating drug delivery. Here we report controlled antibiotic activity and sustained bioavailability from SiNW arrays and also show microstructural manipulations for a tunable release rate. As well, we have demonstrated biodegradability of SiNWs in phosphate buffer saline (PBS) solution. Strikingly suppressed cell and protein adhesion was observed on our SiNW surface, which indicates a reduced probability for biofouling and drug release impediments. Such antibiotic release from the nanowire-structured surface can provide more reliable antibiotic protection at a targeted implantation or biosensor site.

Silicon is one of the most important materials for modern electronics, telecom, and photovoltaic (PV) solar cells. With the rapidly expanding use of Si in the global economy, it would be highly desirable to reduce the overall use of Si material, especially to make the PVs more affordable and widely used as a renewable energy source. Here we report the first successful direction-guided, nano/microshaping of silicon, the intended direction of which is dictated by an applied magnetic field. Micrometer thin, massively parallel silicon sheets, very tall Si microneedles, zigzag bent Si nanowires, and tunnel drilling into Si substrates have all been demonstrated. The technique, utilizing narrow array of Au/Fe/Au trilayer etch lines, is particularly effective in producing only micrometer-thick Si sheets by rapid and inexpensive means with only 5 μm level slicing loss of Si material, thus practically eliminating the waste (and also the use) of Si material compared to the ~200 μm kerf loss per slicing and ~200 μm thick wafer in the typical saw-cut Si solar cell preparation. We expect that such nano/microshaping will enable a whole new family of novel Si geometries and exciting applications, including flexible Si circuits and highly antireflective zigzag nanowire coatings.

Manipulation of cell patterns in three dimensions in a manner that mimics natural tissue organization and function is critical for cell biological studies and likely essential for successfully regenerating tissues--especially cells with high physiological demands, such as those of the heart, liver, lungs, and articular cartilage.(1, 2) In the present study, we report on the feasibility of arranging iron oxide-labeled cells in three-dimensional hydrogels using magnetic fields. By manipulating the strength, shape, and orientation of the magnetic field and using crosslinking gradients in hydrogels, multi-directional cell arrangements can be produced in vitro and even directly in situ. We show that these ferromagnetic particles are nontoxic between 0.1 and 10 mg/mL; certain species of particles can permit or even enhance tissue formation, and these particles can be tracked using magnetic resonance imaging. Taken together, this approach can be adapted for studying basic biological processes in vitro, for general tissue engineering approaches, and for producing organized repair tissues directly in situ.

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This paper describes the development of a new class of N-linked imidazoles as potential pH-sensitive, cleavable linkers for use in cancer drug delivery systems. Kinetic analysis of eight derivatives of N-ethoxybenzylimidazoles (NEBIs) showed that their rates of hydrolysis are accelerated in mild aqueous acidic solutions compared to in solutions at normal, physiological pH. Incorporation of electron donating or electron withdrawing substituents on the phenyl ring of the NEBI resulted in the ability to tune the rates of hydrolysis under mild acidic conditions with half-lives ranging from minutes to months. A derivative of NEBI carrying doxorubicin, a widely used anticancer agent, also showed an increased rate of hydrolysis under mild acid compared to that at normal physiological pH. The doxorubicin analogue resulting from hydrolysis from the NEBI exhibited good cytotoxic activity when exposed to human ovarian cancer cells. These results demonstrate a potentially useful, general strategy for conjugating a wide range of drugs to imidazole-containing delivery vessels via NEBI functionalities for controlled release of therapeutics for drug delivery applications.