Drug-induced liver injury (DILI)
is a frequent cause of hepatic
dysfunction as well as the single most frequent reason for removing
approved medications from the market, and multispectral optoacoustic
tomography (MSOT) is an emerging and noninvasive imaging modality
for diagnosing and monitoring diseases. Herein, we report an activatable
optoacoustic probe for imaging DILI through detecting the activity
of leucine aminopeptidase (LAP). In this probe, an N-terminal leucyl
moiety serving as the LAP recognition element is linked with a chromene-benzoindolium
chromophore via 4-aminobenzylalcohol group. The elevated expression
of hepatic LAP as a result of DILI cleaves the leucyl moiety and causes
the red-shift of the probe’s absorption band, thereby generating
prominent optoacoustic signals for MSOT imaging. During this process,
the probe also exhibits prominent NIR fluorescence, which can be utilized
for fluorescent imaging. More importantly, by rendering stacks of
cross-sectional images as maximal intensity projection (MIP) images,
we could precisely locate the focus of drug-induced liver injury in
mice. This probe is expected to serve a powerful tool for studying
physiological and pathological processes related to LAP.
Gold nanocages (AuNCs) and gold nanoclusters (AuClusters) are two classes of advantageous nanostructures with special optical properties, and many other attractive properties. Integrating them into one nanosystem may achieve greater and smarter performance. Herein, a hybrid gold nanostructure for fluorescent and optoacoustic tomography imaging, controlled release of drugs, and photothermal therapy (PTT) is demonstrated. For this nanodrug (EA–AB), an epidermal growth factor receptor (EGFR) inhibitor erlotinib (EB) is loaded into AuNCs, which are then capped and functionalized by biocompatible AuCluster@BSA (BSA = bovine serum albumin) conjugates via electrostatic interaction. Upon cell internalization, the lysosomal proteases and low pH cause the release of EB from EA–AB, and also induce fluorescence restoration of the AuCluster for imaging. Irradiation with near‐infrared light further promotes the drug release and affords a PTT effect as well. The AuNC‐based nanodrug is optoacoustically active, and its biodistribution and metabolic process have been successfully monitored by whole‐body and 3D multispectral optoacoustic tomography imaging. Owing to the combined actions of PTT and EGFR pathway blockage, EA–AB exhibits marked tumor inhibition efficacy in vivo.
This paper presents an output-capacitor-free adaptively biased low-dropout regulator with subthreshold undershootreduction (ABSTUR LDR) for SoC power management applications. Techniques of adaptive biasing (AB) and Miller compensation with Q-reduction are employed to achieve low-voltage highprecision regulation with extended loop bandwidth while maintaining low quiescent current and high current efficiency. The pass transistor is designed to work in the linear region at heavy load to save silicon area, and a symmetrically matched current-voltage mirror is used to implement the AB scheme with accurate current sensing for the full load range. The dedicated STUR circuit, which is low-voltage compatible and consumes very low current in the steady state, is inserted to momentarily but exponentially increase the gate discharging current of the pass transistor when the LDR output has a large undershoot due to a large step up of the load current. Undershoot voltage is hence dramatically reduced. Stability of the ABSTUR LDR is thoroughly analyzed and tradeoffs between the undershoot-reduction strength and the light load stability are discussed. Features of the proposed ABSTUR LDR are experimentally verified by a prototype fabricated in a standard 0.35-m CMOS process.
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