Engineered Near‐Infrared Fluorescent Protein Assemblies for Robust Bioimaging and Therapeutic Applications

Abstract

Near-infrared (NIR) fluorescence imaging is an evolving field enabling high-resolution imaging and diagnosis in biomedicine. Due to the reduced photon scattering and minimal tissue absorption, fluorescence imaging in the NIR window Fluorescent proteins are investigated extensively as markers for the imaging of cells and tissues that are treated by gene transfection. However, limited transfection efficiency and lack of targeting restrict the clinical application of this method rooted in the challenging development of robust fluorescent proteins for in vivo bioimaging. To address this, a new type of near-infrared (NIR) fluorescent protein assemblies manufactured by genetic engineering is presented. Due to the formation of well-defined nanoparticles and spectral operation within the phototherapeutic window, the NIR protein aggregates allow stable and specific tumor imaging via simple exogenous injection. Importantly, in vivo tumor metastases are tracked and this overcomes the limitations of in vivo imaging that can only be implemented relying on the gene transfection of fluorescent proteins. Concomitantly, the efficient loading of hydrophobic drugs into the protein nanoparticles is demonstrated facilitating the therapy of tumors in a mouse model. It is believed that these theranostic NIR fluorescent protein assemblies, hence, show great potential for the in vivo detection and therapy of cancer.(700-1700 nm) offers increased tissue penetration depths and a better signal-to-noise ratio rendering it ideal for biomedical applications. [1][2][3][4][5][6][7] Currently, NIR fluorescent materials mainly comprise quantum dots, [8][9][10] lanthanide-doped upconverting nanoparticles, [11][12][13] organic small molecules, [14,15] and polymer-based systems. [16] However, long-term toxicity and immunogenicity, non-biodegradability, as well as photo-instability of these non-life-like materials have restricted their translation into clinical applications. [17][18][19][20][21][22] Thus, the development of new fluorophores with increased biocompatibility and biosafety as imaging diagnostic tools is essential for biomedical application.Fluorescent proteins (FPs), such as redshifted fluorescent protein and engineered monomeric near-infrared fluorescent proteins (mIFPs), were proven to be excellent candidates for noninvasive labeling and whole-body imaging in living organisms due to the low light scattering/background noise, reduced autofluorescence, and relatively easy construction procedure. [23][24][25][26][27][28][29][30] Typically, those fluorophores are genetically encoded and must be produced by gene transfection into living cells and animals for bioimaging. However, the transfection efficiency is limited and the FPs expressed by this procedure are unable to target tumors effectively owing to the lack of specific binding sites. [31,32] Moreover, FPs that are expressed by hosts such as Escherichia coli and yeast are rarely reported for direct in vivo bioimaging. This most likely stems from the fast photobleaching in blood protease...

Significantly Improving the Bioefficacy for Rheumatoid Arthritis with Supramolecular Nanoformulations

“…Traditionally, steroids or immune-suppressor compounds are employed for the treatment of RA, whereas it is often complicated by medication resistance, poor bioavailability, and a broad range of adverse effects such as osteoporosis, diabetes, and Typically, the nanotherapeutic with ambient particles size of 10-200 nm might effectively facilitate diffusion of the payloads and increase circulation half-life. [26][27][28] However in the context of immunotherapy of RA, it remains a stark challenge to formulate medications, for example, soluble and bioactive proteins into well-defined and easy-to-disassemble nanoparticulate systems for enhanced bioefficacy.…”

Anisotropic Protein Organofibers Encoded With Extraordinary Mechanical Behavior for Cellular Mechanobiology Applications

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“…Particles can be composed of biocompatible materials, metallic materials, magnetic materials or optical materials, [1][2][3][4] and have very rich functionality, showing broad application prospects. [5][6][7][8][9][10][11][12][13][14][15] Nanoprecipitation is a green bottom-up technique to prepare particles through nucleation and growth. [16][17][18] Generally, the polymer is dissolved in a good solvent, which is then mixed with an anti-solvent.…”

“…Particles can be composed of biocompatible materials, metallic materials, magnetic materials or optical materials, [1–4] and have very rich functionality, showing broad application prospects [5–15] . Nanoprecipitation is a green bottom‐up technique to prepare particles through nucleation and growth [16–18] .…”