RBC-hitchhiking regime is shown without prolongation of nanoparticle blood circulation but with the record 120-fold boost of particle delivery to lungs. The approach is efficient for treatment of pulmonary metastases.

Nanoparticles with biocomputing capabilities could potentially be used to create sophisticated robotic devices with a variety of biomedical applications, including intelligent sensors and theranostic agents. DNA/RNA-based computing techniques have already been developed that can offer a complete set of Boolean logic functions and have been used, for example, to analyse cells and deliver molecular payloads. However, the computing potential of particle-based systems remains relatively unexplored. Here, we show that almost any type of nanoparticle or microparticle can be transformed into autonomous biocomputing structures that are capable of implementing a functionally complete set of Boolean logic gates (YES, NOT, AND and OR) and binding to a target as result of a computation. The logic-gating functionality is incorporated into self-assembled particle/biomolecule interfaces (demonstrated here with proteins) and the logic gating is achieved through input-induced disassembly of the structures. To illustrate the capabilities of the approach, we show that the structures can be used for logic-gated cell targeting and advanced immunoassays.

Accurate and precise drug delivery is the key to successful therapy. Monoclonal antibodies, which can transport therapeutic payload to cells expressing specific markers, have paved the way for targeted drug delivery and currently show tremendous clinical success. However, in those abundant cases, when a disease cannot be characterized by a single specific marker, more sophisticated drug delivery systems are required. To enhance targeting accuracy, diverse smart materials have been proposed that can also react to stimuli like variations of pH, temperature, magnetic field, etc. Furthermore, over the past few years a new category of smart materials has emerged, which can not only respond to virtually any biochemical or physical stimulus but also simultaneously analyze several cues and, moreover, can be programmed to use Boolean logic for such analysis. These advanced biocomputing agents have the potential to become a basis for future nanorobotic devices that could overcome some of the grand challenges of modern biomedicine. Here, with a brief introduction to the multidisciplinary field of biomolecular computing, we will review the concepts of nanomaterials with built-in biocomputing capabilities, which can be potentially used for drug delivery and other theranostic applications.

We present a multiplex quantitative lateral flow (LF) assay for simultaneous on-site detection of botulinum neurotoxin (BoNT) types A, B, and E in complex matrixes, which is innovative by virtually no sacrifice in performance while transition from the single-plex assays and by characteristics on the level of laboratory quantitative methods. The novel approach to easy multiplexing is realized via joining an on-demand set of single-plex LF strips, which employ magnetic nanolabels, into a miniature cylinder cartridge that mimics LF strip during all assay stages. The cartridge is read out by an original portable multichannel reader based on the magnetic particle quantification technique. The developed reader offers the unmatched 60 zmol detection limit and 7-order linear dynamic range for volumetric registration of magnetic labels inside a cartridge of several millimeters in diameter regardless of its optical transparency. Each of the test strips, developed here as building blocks for the multiplex assay, can be used "as is" for autonomous quantitative single-plex detection with the same measuring setup, exhibiting the limits of detection (LOD) of 0.22, 0.11, and 0.32 ng/mL for BoNT-A, -B, and -E, respectively. The proposed multiplex assay has demonstrated the remarkably similar LOD values of 0.20, 0.12, 0.35 ng/mL under the same conditions. The multiplex assay performance was successfully validated by BoNT detection in milk and apple and orange juices. The developed methods can be extended to other proteins and used for rapid multianalyte tests for point-of-care in vitro diagnostics, food analysis, biosafety and environmental monitoring, forensics, and security, etc.

A bioengineering method for self-assembly of multifunctional superstructures with in-advance programmable properties has been proposed. The method employs two unique proteins, barnase and barstar, to rapidly join the structural components together directly in water solutions. The properties of the superstructures can be designed on demand by linking different agents of various sizes and chemical nature, designated for specific goals. As a proof of concept, colloidally stable trifunctional structures have been assembled by binding together magnetic particles, quantum dots, and antibodies using barnase and barstar. The assembly has demonstrated that the bonds between these proteins are strong enough to hold macroscopic (5 nm-3 μm) particles together. Specific interaction of such superstructures with cancer cells resulted in fluorescent labeling of the cells and their responsiveness to magnetic field. The method can be used to join inorganic moieties, organic particles, and single biomolecules for synergistic use in different applications such as biosensors, photonics, and nanomedicine.superstructures | cancer cells | targeting | fusion proteins | magnetic nanoparticles R ecently, nanoparticles have become attractive objects for life science applications, in particular, in such rapidly growing areas as express diagnostics and advanced medical treatment. Encapsulation of nanoparticles with drug molecules (1, 2) or attaching them to viruses, bacteria, etc. are of special interest. Time-controlled release of the absorbed drugs would be advantageous for treatment of many diseases, e.g. diabetes, because of a decreased number of injections compared to that of molecular insulin. Furthermore, fluorescent or colored particles such as quantum dots (QD) (3), nanodiamonds (4), and gold nanoparticles (5) can be used for diagnostics as markers that provide visual information about the distribution of labeled agents in tissues and blood. Magnetic particles (MP) (6) can be also used as efficient labels for MRI diagnostics and can be precisely quantified even inside a living organism by an external induction probe (7,8). At present, MP are widely studied for hyperthermia of tumors by heating in an AC magnetic field and for targeted delivery of drugs by magnetic field gradients, to avoid systemic intoxication of the organism (9, 10). Specific immunological targeting of nanoparticles by antibodies against pathogenic cells is another noteworthy application. Not only does it allow marking tumors for accurate dissection, but it also enhances drug delivery to the target cells.The above-mentioned functional aspects of nanoparticles are brought into play in many life science applications. In certain cases, however, it would be beneficial to use multifunctional structures (11-13), which consist of several types of particles. Extensive studies were devoted to the synthesis of hybrid complexes of magnetic particles and different fluorophores (quantum dots or conventional chemical dyes) to allow visual MP tracking. Most approaches (14-16) emp...

Method of highly sensitive registration of magnetic nanoparticles by their nonlinear magnetization is used in a novel sandwich-type immunoassay for detection of staphylococcal toxins in complex media of virtually any volume, with increasing sensitivity at higher sample volume. The signal is read out from the entire volume of a nontransparent 3D fiber structure employed as a solid phase, which provides large reaction surface, quick reagent mixing, as well as antigen immunofiltration directly in the course of the assay. The method has demonstrated near-linear dose-response curves within a wide range of ~3 decades, while detection of staphylococcal enterotoxin A (SEA) and toxic shock syndrome toxin (TSST) in neat milk without sample preparation. The limits of detection (LOD) as low as 4 and 10 pg/mL for TSST and SEA, respectively, were obtained in 2-h format using 30-mL samples. The second, 25-min format, showed the LOD of 0.1 and 0.3 ng/mL for the same toxins in a 150 μL sample. The developed immunoassay can be applied in food safety control, in vitro diagnostics, and veterinary for a variety of research from express tests in the field to highly sensitive laboratory tests.

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