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At the present time a new direction of theranostics associated with using of nanostructured multifunctional carriers is developed rapidly. Appreciative examples of such carriers are core-shell nanoparticles, liposomes, polymer micelles, capsules produced by Layer by Layer assembly (LbL) method. Every type of nanostructured carriers has its own advantages and disadvantages. Undoubted advantages of LbL capsules are high loading capacity, wide range of possible internal payloads and wide possibilities of controlling physical and chemical properties of nanostructured carriers by variation of shell structure, thickness and its chemical composition [М.Delcea, et al, Adv. drug delivery reviews, 2011, 63(9), 730, A.S.Timin, et al, Adv. Mater. Interfaces,2016, 4, 1600338]. Application of nanostructured carriers is limited by absence of methods for its in vivo visualization with sufficient spatial resolution and significant tissue penetration depth [A.S.Timin, et al, Adv. Mater. Interfaces, 2016, 4,1600338]. One of the method that allows to visualize and to detect the nanostructured carriers efficiently is a photoacoustic (PA) method. PA approach allows to use the photoacoustic cytometry in vivo [E.I. Galanzha et al, Cancer Res. 2009, 69, 7926]. It is also very important for detection and killing of free circulating cancer cells required for early cancer diagnostics and decreasing the metastases probability [E.I. Galanzha, et al, J. Biophotonics, 2009, 2, 725]. Unique combination of photoacoustic cytometry and nanostructured carriers prepared by LbL assembly approach gives clinicians and researchers significant advantages in the developing of new therapy method based on delivery of nanostructured carriers loaded by bioactive substances into lesion focus and also their visualization and remote controlled release of encapsulated bioactive substances using PA approach. Visualization of two types of nanostructured carriers produced by LbL assembly method was demonstrated recently in diluted and undiluted blood [E.I. Galanzha, et al, J. Biophotonics, 2009, 2, 725]. It was established that hollow microcapsules exhibited greater photoacoustic signal comparing to core-shell type of microparticles with the same composition of polymeric shell [E.I. Galanzha, et al, J. Biophotonics, 2009, 2, 725]. Nevertheless, there are no known examples of in vivo photoacoustic detection of LbL nanostructured carriers, therefore the main goal of present study is formation of biocompatible nanostructured carriers (BNCs) that will exhibit giant photoacoustic signal allowing in vivo detection of such structures. It was demonstrated for the first time, the super (giant) PA contrast of BNCs both in vitro and in vivo. It was verified the unique PA characteristics of these advanced contrast agents using PA flow cytometry diagnostic platform. The obtained data suggest the high PA contrast of BNCs that can be associated with synergistic plasmonic, thermal and acoustic effects, especially in nonlinear mode with nanobubble formation in overheated absorbing layers, in particular gold nanoclusters between two light transparent shells.
This work was partly supported by RFBR (project №18-29-08046), the Government of the Russian Federation (grant no. 14.Z50.31.0044 to support scientific research projects implemented under the supervision of leading scientists at Russian institutions and Russian institutions of higher education) and Saratov State University.
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