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.
Delivery of particle-based theranostic agents via their transportation on the surfaces of red blood cells, commonly referred to as RBC-hitchhiking, has historically been developed as a promising strategy for increasing the extremely poor blood circulation lifetime, primarily, of the large-sized sub-micron agents. Here, we show for the first time that RBC-hitchhiking can be extremely efficient for nanoparticle delivery and tumor treatment even in those cases when no circulation prolongation is observed. Specifically, we demonstrate that RBC-hitchhiking of certain small 100 nm particles, unlike that of the conventional sub-micron ones, can boost the delivery of non-targeted particles to lungs up to a record high value of 120-fold (and up to 40% of the injected dose). To achieve this remarkable result, we screened sub-200 nm nanoparticles of different sizes, polymer coatings and ζ-potentials and identified particles with the optimal RBC adsorption/desorption behavior. Furthermore, we demonstrated that such RBC-mediated rerouting of particles to lungs can be used to fight pulmonary metastases of aggressive melanoma B16-F1. Our findings could change the general paradigm of drug delivery for cancer treatment with RBC-hitchhiking. It is not the blood circulation lifetime that is the key factor for nanoparticle efficiency, but rather the complexation of nanoparticles with the RBC. The demonstrated technology could become a valuable tool for development of new strategies based on small nanoparticles for the treatment of aggressive and small-cell types of cancer as well as other lung diseases.
Conditions at which phase of light demonstrates a markedly different behavior for close values of system parameters as well as the Heaviside jump are discussed and explained in terms of phase topology. On this basis, a method of interferometric surface plasmon resonance imaging is proposed and applied to develop ultrasensitive affinity array sensors with a monoatomic thickness resolution.