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Endosomal escape remains a central issue limiting the high protein expression of mRNA therapeutics. Here, we present second near‐infrared (NIR‐II) lipid nanoparticles (LNPs) containing pH activatable NIR‐II dye conjugated lipid (Cy‐lipid) for potentiating mRNA delivery efficiency via a stimulus‐responsive photothermal‐promoted endosomal escape delivery (SPEED) strategy. In acidic endosomal microenvironment, Cy‐lipid is protonated and turns on NIR‐II absorption for light‐to‐heat transduction mediated by 1064 nm laser irradiation. Then, the heat‐promoted LNPs morphology change triggers rapid escape of NIR‐II LNPs from the endosome, allowing about 3‐fold enhancement of enhanced green fluorescent protein (eGFP) encoding mRNA translation capacity compared to the NIR‐II light free group. In addition, the bioluminescence intensity induced by delivered luciferase encoding mRNA in the mouse liver region shows positive correlation with incremental radiation dose, indicating the validity of the SPEED strategy. [ABSTRACT FROM AUTHOR]

We present a second near‐infrared (NIR‐II) self‐checking molecule, LET‐1052, for acidic tumor microenvironment (TME) turn‐on photothermal therapy (PTT), followed by viscosity based therapeutic efficacy evaluation by itself in two independent channels, denoted as "self‐checking" strategy. In acidic TME, LET‐1052 was protonated and turned on NIR‐II absorption for PTT under 1064 nm laser irradiation. Subsequently, PTT‐induced cellular death increases intracellular viscosity, which inhibited the intramolecular rotation of LET‐1052, resulting in the enhancement of NIR‐I fluorescence for real‐time evaluation of PTT efficacy. After PTT of tumor‐bearing mice for different periods of NIR‐II laser irradiation, NIR‐I fluorescence in the tumor region showed positive correlation with tumor growth inhibition rate, demonstrating reliable and prompt prediction of PTT efficacy. The strategy may be expanded for instant evaluation of other therapeutic modalities for personalized medicine. [ABSTRACT FROM AUTHOR]

Early detection of kidney disease is of vital importance due to its current prevalence worldwide. Fluorescence imaging, especially in the second near‐infrared window (NIR‐II) has been regarded as a promising technique for the early diagnosis of kidney disease due to the superior resolution and sensitivity. However, the reported NIR‐II organic renal‐clearable probes are hampered by their low brightness (ϵmaxΦf>1000 nm<10 M−1 cm−1) and limited blood circulation time (t1/2<2 h), which impede the targeted imaging performance. Herein, we develop the aza‐boron‐dipyrromethene (aza‐BODIPY) brush macromolecular probes (Fudan BDIPY Probes (FBP 912)) with high brightness (ϵmaxΦf>1000 nm≈60 M−1 cm−1), which is about 10‐fold higher than that of previously reported NIR‐II renal‐clearable organic probes. FBP 912 exhibits an average diameter of ≈4 nm and high renal clearance efficiency (≈65 % excretion through the kidney within 12 h), showing superior performance for non‐invasively diagnosis of renal ischemia‐reperfusion injury (RIR) earlier than clinical serum‐based protocols. Additionally, the high molecular weight polymer brush enables FBP 912 with prolonged circulation time (t1/2≈6.1 h) and higher brightness than traditional PEGylated renal‐clearable control fluorophores (t1/2<2 h), facilitating for 4T1 tumor passive targeted imaging and renal cell carcinoma active targeted imaging with higher signal‐to‐noise ratio and extended retention time. [ABSTRACT FROM AUTHOR]

Abstract: A small‐molecule fluorophore FD‐1080 with both excitation and emission in the NIR‐II region has been successfully synthesized for in vivo imaging. A heptamethine structure is designed to shift the absorption and emission into NIR‐II region. Sulphonic and cyclohexene groups are introduced to enhance its water solubility and stability. The quantum yield of FD‐1080 is 0.31 %, and can be increased to 5.94 % after combining with fetal bovine serum (FBS). Significantly, 1064 nm NIR‐II excitation was demonstrated with the high tissue penetration depth and superior imaging resolution compared to previously reported NIR excitation from 650 nm to 980 nm. FD‐1080 is not only capable of realizing non‐invasive high‐resolution deep‐tissue hindlimb vasculature and brain vessel bioimaging, but also quantifying the respiratory rate based on the dynamic imaging of respiratory craniocaudal motion of the liver for the awake and anaesthetized mouse. [ABSTRACT FROM AUTHOR]

Effective delivery of imaging agents or therapeutics to the brain has remained elusive due to the poor blood-brain barrier (BBB) permeability, resulting in the apparent risks of inefficient diagnosis and therapeutic agents for brain disease. Herein, we report on the surface roughness mediated BBB transportation for the first time. The lanthanide-based core/shell/shell structured NaYF 4 :Yb,Er@NaGdF 4 :Yb@NaNdF 4 :Yb nanoplates with controllable surface roughness and multi-model bioimaging features were synthesized and used to evaluate the surface roughness dependent BBB permeability without any surface bio-functionalization. By controlling the kinetics of the shell coating process, the hexagon-disc, multi-petals and six-petals nanoplates with different surface roughness can be obtained. Comparing with the NPs with less Ra and receptor-conjugated NPs, the obtained six-petals nanoplates with highest roughness exhibit excellent performance in BBB transportation and tumor targeting, which lay solid foundation for the diagnosis and the therapy of brain tumor. [ABSTRACT FROM AUTHOR]