Two-in-one sensor of refractive index and Raman scattering using hollow-core microstructured optical waveguides for colloid characterization.

Hollow-core microstructured optical waveguides (HC-MOW) have recently emerged in sensing technologies, including the gas and liquid detection for industrial as well as clinical applications. Antiresonant HC-MOW provide capabilities for applications in refractive index (RI) sensing, while the long optical path for analyte-light interaction in HC-MOW leads to increased sensitivity of sensor based on Raman scattering signal measurements. In this study, we developed a two-in-one sensor device using HC-MOW for RI and Raman scattering detection. The performance of the sensor was evaluated by characterizing protein-copolymer multicomponent colloids, specifically, bovine serum albumin (BSA) and poly(N - vinyl-2 -pyrrolidone-co-acrylic acid) P(VP-AA) nano-sized complexes and microbubbles of the corresponding shell. Monocomponent solutions showed linear dependencies of RI and characteristic Raman peak intensities on mass concentration. Multicomponent Raman sensing of BSA@P(VP-AA) complexes and microbubbles revealed that changes in P(VP-AA) characteristic peak intensities can describe interactions between components needed to produce colloid systems. RI sensing of multicomponent colloids demonstrated linear dependence on total mass concentrations for BSA@P(VP-AA) complexes, while corresponding BSA@P(VP-AA) microbubbles can be detected with concentrations as high as 4.0 × 108 MB/mL. Therefore, the developed two-in-one sensor of RI and Raman scattering can be used the robust characterization of albumin-based colloids designed for therapeutic and diagnostic needs.

Modification of bacterial cells for in vivo remotely guided systems.

It was shown recently that bacterial strains, which can act specifically against malignant cells, can be used efficiently in cancer therapy. Many appropriate bacterial strains are either pathogenic or invasive and there is a substantial shortage of methods with which to monitor in vivo the distribution of bacteria used in this way. Here, it is proposed to use a Layer-by-Layer (LbL) approach that can encapsulate individual bacterial cells with fluorescently labeled polyelectrolytes (PE)s and magnetite nanoparticles (NP)s. The NP enable remote direction in vivo to the site in question and the labeled shells in the far-red emission spectra allow non-invasive monitoring of the distribution of bacteria in the body. The magnetic entrapment of the modified bacteria causes the local concentration of the bacteria to increase by a factor of at least 5. The PEs create a strong barrier, and it has been shown in vitro experiments that the division time of bacterial cells coated in this way can be regulated, resulting in control of their invasion into tissues. That animals used in the study survived and did not suffer septic shock, which can be attributed to PE capsules that prevent release of endotoxins from bacterial cells.

Sentinel lymph node detection by combining nonradioactive techniques with contrast agents: State of the art and prospects.

The status of sentinel lymph nodes (SLNs) has a substantial prognostic value because these nodes are the first place where cancer cells accumulate along their spreading route. Routine SLN biopsy ("gold standard") involves peritumoral injections of radiopharmaceuticals, such as technetium-99m, which has obvious disadvantages. This review examines the methods used as "gold standard" analogs to diagnose SLNs. Nonradioactive preoperative and intraoperative methods of SLN detection are analyzed. Promising photonic tools for SLNs detection are reviewed, including NIR-I/NIR-II fluorescence imaging, photoswitching dyes for SLN detection, in vivo photoacoustic detection, imaging and biopsy of SLNs. Also are discussed methods of SLN detection by magnetic resonance imaging, ultrasonic imaging systems including as combined with photoacoustic imaging, and methods based on the magnetometer-aided detection of superparamagnetic nanoparticles. The advantages and disadvantages of nonradioactive SLN-detection methods are shown. The review concludes with prospects for the use of conservative diagnostic methods in combination with photonic tools.

Biodegradable polyelectrolyte/magnetite capsules for MR imaging and magnetic targeting of tumors.

Rationale: The tireless research for effective drug delivery approaches is prompted by poor target tissue penetration and limited selectivity against diseased cells. To overcome these issues, various nano- and micro-carriers have been developed so far, but some of them are characterized by slow degradation time, thus hampering repeated drug administrations. The aim of this study was to pursue a selective delivery of magnetic biodegradable polyelectrolyte capsules in a mouse breast cancer model, using an external magnetic field. Methods: Four different kinds of magnetic polyelectrolyte capsules were fabricated via layer-by-layer assembly of biodegradable polymers on calcium carbonate templates. Magnetite nanoparticles were embedded either into the capsules' shell (sample S) or both into the shell and the inner volume of the capsules (samples CnS, where n is the number of nanoparticle loading cycles). Samples were first characterized in terms of their relaxometric and photosedimentometric properties. In vitro magnetic resonance imaging (MRI) experiments, carried out on RAW 264.7 cells, allowed the selection of two lead samples that proceeded for the in vivo testing on a mouse breast cancer model. In the set of in vivo experiments, an external magnet was applied for 1 hour following the intravenous injection of the capsules to improve their delivery to tumor, and MRI scans were acquired at different time points post administration. Results: All samples were considered non-cytotoxic as they provided more than 76% viability of RAW 264.7 cells upon 2 h incubation. Sample S appeared to be the most efficient in terms of T2-MRI contrast, but the less sensitive to external magnet navigation, since no difference in MRI signal with and without the magnet was observed. On the other side, sample C6S was efficiently delivered to the tumor tissue, with a three-fold T2-MRI contrast enhancement upon the external magnet application. The effective magnetic targeting of C6S capsules was also confirmed by the reduction in T2-MRI contrast in spleen if compared with the untreated with magnet mice values, and the presence of dense and clustered iron aggregates in tumor histology sections even 48 h after the magnetic targeting. Conclusion: The highlighted strategy of magnetic biodegradable polyelectrolyte capsules' design allows for the development of an efficient drug delivery system, which through an MRI-guided externally controlled navigation may lead to a significant improvement of the anticancer chemotherapy performance.

Endovascular addressing improves the effectiveness of magnetic targeting of drug carrier. Comparison with the conventional administration method.

Many nanomedicine approaches are struggling to reach high enough effectiveness in delivery if applied systemically. The perspective is sought to explore the clinical practices currently used for localized treatment. In this study, we combine in vivo targeting of carriers sensitive to the external magnetic field with clinically used endovascular delivery to specific site. Fluorescent micron-size capsules made of biodegradable polymers and containing magnetite nanoparticles incorporated in the capsule wall were explored in vivo using Near-Infrared Fluorescence Live Imaging for Real-Time. Comparison of systemic (intravenous) and directed (intra-arterial) administration of the magnetic microcapsule targeting in the hindpaw vessels demonstrated that using femoral artery injection in combination with magnetic field exposure is 4 times more efficient than tail vein injection. Thus, endovascular targeting significantly improves the capabilities of nanoengineered drug delivery systems reducing the systemic side effects of therapy.

Submicron-Sized Nanocomposite Magnetic-Sensitive Carriers: Controllable Organ Distribution and Biological Effects.

Although new drug delivery systems have been intensely developed in the past decade, no significant increase in the efficiency of drug delivery by nanostructure carriers has been achieved. The reasons are the lack of information about acute toxicity, the influence of the submicron size of the carrier and difficulties with the study of biodistribution in vivo. Here we propose, for the first time in vivo, new nanocomposite submicron carriers made of bovine serum albumin (BSA) and tannic acid (TA) and containing magnetite nanoparticles with sufficient content for navigation in a magnetic field gradient on mice. We examined the efficacy of these submicron carriers as a delivery vehicle in combination with magnetite nanoparticles which were systemically administered intravenously. In addition, the systemic toxicity of this carrier for intravenous administration was explicitly studied. The results showed that (BSA/TA) carriers in the given doses were hemocompatible and didn't cause any adverse effect on the respiratory system, kidney or liver functions. A combination of gradient-magnetic-field controllable biodistribution of submicron carriers with fluorescence tomography/MRI imaging in vivo provides a new opportunity to improve drug delivery efficiency.

Transfer of cells with uptaken nanocomposite, magnetite-nanoparticle functionalized capsules with electromagnetic tweezers.

Targeted cell delivery via magnetically sensitive microcapsules of an applied magnetic field would advance localized cell transplantation therapy, by which healthy cells can be introduced into tissues to repair damaged or diseased organs. In the present research, we implement magnetically sensitive cells via an uptake of microcapsules containing magnetic nanoparticles in their walls. As is shown in an example of the MA-104 cell line, the magnetic polyelectrolyte multilayer capsules have no toxicity effect on the cells after internalization. Microscopy methods have been used to evaluate the uptake of capsules by the cells. Magnetically sensitive cells are retained in the capillary flow when the magnetic gradient field is applied (<200 T m-1), but they proliferate at the site of retention for several days after the magnet is removed. As an example of cell manipulation, we have demonstrated a novel methodology for cell sheet isolation and transfer using cells impregnated with magnetic microcapsules. A weak enzyme treatment is used to facilitate tissue engineering assemblies by cell monolayer deposition. This type of cell monolayer assembly has provided a 3D tissue engineering construction using an externally applied magnetic field, which is modelled in this study. The approach presented in this work opens perspectives for preclinical studies of tissue and organ repair.

In vitro and in vivo MRI visualization of nanocomposite biodegradable microcapsules with tunable contrast.

Microcapsules, made of biodegradable polymers, containing magnetite nanoparticles with tunable contrast in both the T1 and T2 MRI modes, were successfully prepared using a layer-by-layer approach. The MRI contrast of the microcapsules was shown to depend on the distance between magnetite nanoparticles in the polymeric layers, which is controlled by their concentration in the microcapsule shell. A fivefold increase in the average distance between the nanoparticles in the microcapsule shell led to a change in the intensity of the MR signal of 100% for both the T1 and T2 modes. Enzyme treatment of biodegradable shells resulted in a change of the microcapsules' MRI contrast. In vivo degradation of nanocomposite microcapsules concentrated in the liver after intravenous injection was demonstrated by MRI. This method can be used for the creation of a new generation of drug delivery systems, including drug depot, with combined navigation, visualization and remote activated release of bioactive substances in vivo.