Low intensity focused ultrasound responsive microcapsules for non-ablative ultrafast intracellular release of small molecules.

Focused ultrasound (FU) is in demand for clinical cancer therapy, but the possible thermal injury to the normal peripheral tissues limits the usage of the ablative FU for tumors with a large size; therefore research efforts have been made to minimize the possible side effects induced by the FU treatment. Non-ablative focused ultrasound assisted chemotherapy could open a new avenue for the development of cancer therapy technology. Here, low intensity focused ultrasound (LIFU) for controlled quick intracellular release of small molecules (Mw ≤ 1000 Da) without acute cell damage is demonstrated. The release is achieved by a composite poly(allylamine hydrochloride) (PAH)/poly-(sodium 4-styrenesulfonate) (PSS)/SiO2 microcapsules which are highly sensitive to LIFU and can be effectively broken by weak cavitation effects. Most PAH/PSS/SiO2 capsules in B50 rat neuronal cells can be ruptured and release rhodamine B (Rh-B) into the cytosol within only 30 s of 0.75 W cm-2 LIFU treatment, as demonstrated by the CLSM results. While the same LIFU treatment shows no obvious damage to cells, as proved by the live/dead experiment, showing that 90% of cells remain alive.

Focused ultrasound-mediated fluorescence of composite microcapsules loaded with magnetite nanoparticles: In vitro and in vivo study.

High intensity focused ultrasound (HIFU) is widely used in medical practice, including cancer therapy. Also this approach is promising for remote release of encapsulated drugs in various other biomedical applications where local treatment is needed. Our approach underpins the minimization of HIFU impact on possible degradation of biological tissues and expand the use of HIFU in the controlled release of encapsulated drugs. We demonstrated the efficient ultrasound-induced release of labeled protein (Cy7-BSA) from elaborated nanocomposite microcapsules in vitro an in vivo. The capsule fabrication was done using combination of recently developed freezing-induced loading (FIL) technique and Layer-by-Layer assembly (LbL) used for the preparation of complex multilayer BSA/tannic acid nanocomposite capsules sensitive to HIFU. These capsules contain NIR fluorescent Cy7-labeled BSA in the shell for tracking in vivo and the high concentration of labels inside the capsules resulted in self-quenching provides the real-time detection of the protein once it is released from the capsule. Ultrasound-induced release in vivo of Cy7-labeled BSA initially quenched by magnetite nanoparticles was confirmed by fluorescent tomography. The significant decrease of Cy7 fluorescence under HIFU treatment in vitro was found to be due to a generation of reactive oxygen species and fast dye oxidation. Our results demonstrate that adapted HIFU setup can be used for the directed release of encapsulated substances in vivo under tissue compatible NIR monitoring by fluorescent tomography.

Polylactic acid nano- and microchamber arrays for encapsulation of small hydrophilic molecules featuring drug release via high intensity focused ultrasound.

Long term encapsulation combined with spatiotemporal release for a precisely defined quantity of small hydrophilic molecules on demand remains a challenge in various fields ranging from medical drug delivery, controlled release of catalysts to industrial anti-corrosion systems. Free-standing individually sealed polylactic acid (PLA) nano- and microchamber arrays were produced by one-step dip-coating a PDMS stamp into PLA solution for 5 s followed by drying under ambient conditions. The wall thickness of these hydrophobic nano-microchambers is tunable from 150 nm to 7 µm by varying the PLA solution concentration. Furthermore, small hydrophilic molecules were successfully in situ precipitated within individual microchambers in the course of solvent evaporation after sonicating the PLA@PDMS stamp to remove air-bubbles and to load the active substance containing solvent. The cargo capacity of single chambers was determined to be in the range of several picograms, while it amounts to several micrograms per cm2. Two different methods for sealing chambers were compared: microcontact printing versus dip-coating whereby microcontact printing onto a flat PLA sheet allows for entrapment of micro-air-bubbles enabling microchambers with both ultrasound responsiveness and reduced permeability. Cargo release triggered by external high intensity focused ultrasound (HIFU) stimuli is demonstrated by experiment and compared with numerical simulations.

Spin noise explores local magnetic fields in a semiconductor.

Rapid development of spin noise spectroscopy of the last decade has led to a number of remarkable achievements in the fields of both magnetic resonance and optical spectroscopy. In this report, we demonstrate a new - magnetometric - potential of the spin noise spectroscopy and use it to study magnetic fields acting upon electron spin-system of an n-GaAs layer in a high-Q microcavity probed by elliptically polarized light. Along with the external magnetic field, applied to the sample, the spin noise spectrum revealed the Overhauser field created by optically oriented nuclei and an additional, previously unobserved, field arising in the presence of circularly polarized light. This "optical field" is directed along the light propagation axis, with its sign determined by sign of the light helicity. We show that this field results from the optical Stark effect in the field of the elliptically polarized light. This conclusion is supported by theoretical estimates.