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Organic semiconducting nanoprobe with redox-activatable NIR-II fluorescence for <i>in vivo</i> real-time monitoring of drug toxicity
摘要： An activatable organic semiconducting nanoprobe that specifically turns on its second near-infrared window fluorescence upon being exposed to nitric oxide stimuli was developed for in vivo, in situ, real-time and high-spatial-resolution mapping of drug-induced hepatotoxicity.
关键词： drug toxicity,nitric oxide,NIR-II fluorescence,hepatotoxicity,redox-activatable,in vivo monitoring,Organic semiconducting nanoprobe
更新于2025-09-19 17:15:36
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Photoacoustic Imaging Quantifies Drug Release from Nanocarriers via Redox Chemistry of Dye‐Labeled Cargo
摘要： There have been remarkable advances in imaging drug nanocarriers, but there are few real-time imaging strategies to determine if the cargo has been released from the carrier. This is important because the pharmacokinetics and pharmacodynamics of the carrier can often be dramatically decoupled from that of the cargo. Thus, new tools are clearly needed to image the timing and quantity of drug release from nanocarriers. Here, we describe a simple strategy for photoacoustic monitoring of drug release based on the redox chemistry of methylene blue, which offers predictable redox chemistry: It can transition from the oxidized state with a bright blue color and robust photoacoustic signal to the reduced state that the transparent with no photoacoustic signal. We locked this drug-dye conjugate into a reduced state inside of a nanoparticle with no photoacoustic signal. As the drug is released from the carrier, the dye is oxidized for quantification with photoacoustic imaging. We first prepared paclitaxel-methylene blue conjugate (PTX-MB) with strong absorbance at 640 nm and photoacoustic intensity proportional to its concentration. This cargo was co-encapsulated in a poly(lactic-co-glycolic acid) nanoparticle with a dithiothreitol reducing agent. The IC50 of PTX-MB-loaded NPs (PTX-MB @ PLGA NPs) was 78 μg mL-1. We then used the redox reaction of PTX-MB to monitor its release from poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). In vitro drug-release in phosphate buffer saline with 20% v/v normal mice serum showed a 670-fold increase in photoacoustic signal. The particles showed an initial burst release (25%) during the first 24 hours. After 24 hours, a sustained release was observed through 120 hours leading to cumulative release of 40.6% of PTX-MB. In vivo drug release study in mice for a duration of 12 hours showed a photoacoustic signal enhancement of up to 649% after 10 hours. We then used this system to treat an orthotopic model of colon cancer via luciferase-positive CT26 cells. Our data showed that tumor burden decreased by 44.7% ± 4.8% when treated with the PTX-MB @ PLGA NPs versus the empty PLGA carrier. This work presents a direct strategy to simultaneously monitor drug release biodistribution.
关键词： Photoacoustic imaging,Paclitaxel,Image-guided drug delivery,PLGA nanoparticles,Drug-release,Cancer therapy,in vivo monitoring
更新于2025-09-16 10:30:52