Dual-Responsive Curcumin-Loaded Nanoparticles for the Treatment of Cisplatin-Induced Acute Kidney Injury.

Acute kidney injury (AKI) has been a global public health concern leading to high patient morbidity and mortality in the world. Nanotechnology-mediated antioxidative therapy has facilitated the treatment of AKI. Herein, a hierarchical curcumin-loaded nanodrug delivery system (NPS@Cur) was fabricated for antioxidant therapy to ameliorate AKI. The nanoplatform could respond to subacidic and reactive oxygen species (ROS) microenvironments. The subacidic microenvironment led to a smaller size (from 140.9 to 99.36 nm) and positive charge (from -4.9 to 12.6 mV), contributing to the high accumulation of nanoparticles. An excessive ROS microenvironment led to nanoparticle degradation and drug release. In vitro assays showed that NPS@Cur could scavenge excessive ROS and relieve oxidative stress in H2O2-induced HK-2 cells through reduced apoptosis, activated autophagy, and decreased endoplasmic reticulum stress. Results from cisplatin-induced AKI models revealed that NPS@Cur could effectively alleviate mitochondria injury and protect kidneys via antioxidative protection, activated autophagy, decreased endoplasmic reticulum stress, and reduced apoptosis. NPS@Cur showed excellent biocompatibility and low toxicity to primary tissues in mice. These results revealed that NPS@Cur may be a potential therapeutic strategy for efficiently treating cisplatin or other cause-induced AKI.

An Activatable Probe with Aggregation-Induced Emission for Detecting and Imaging Herbal Medicine Induced Liver Injury with Optoacoustic Imaging and NIR-II Fluorescence Imaging.

Whilte herbal medicines are widely used for health promotion and therapy for chronic conditions, inappropriate use of them may cause adverse effects like liver injury, and accurately evaluating their hepatotoxicity is of great significance for public health. Herein, an activatable probe QY-N for diagnosing herbal-medicine-induced liver injury by detecting hepatic NO with NIR-II fluorescence and multispectral optoacoustic tomography (MSOT) imaging is demonstrated. The probe includes a bismethoxyphenyl-amine-containing dihydroxanthene serving as electron donor, a quinolinium as electron acceptor, and a butylamine as recognition group and fluorescence quencher. The hepatic level of NO reacts with butylamine, thereby generating the activated probe QY-NO which exhibits a red-shifted absorption band (700-850 nm) for optoacoustic imaging and generates strong emission (910-1110 nm) for NIR-II fluorescence imaging. QY-NO is aggregation-induced-emission (AIE) active, which ensures strong emission in aggregated state. QY-N is utilized in the triptolide-induced liver injury mouse model, and experimental results demonstrate the QY-N can be activated by hepatic NO and thus be used in detecting herbal-medicine-induced liver injury. The temporal and spatial information provided by three-dimensional MSOT images well delineates the site and size of liver injury. Moreover, QY-N has also been employed to monitor rehabilitation of liver injury during treatment process.

A Gold Nanocage/Cluster Hybrid Structure for Whole-Body Multispectral Optoacoustic Tomography Imaging, EGFR Inhibitor Delivery, and Photothermal Therapy.

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.

A conjugated-polymer-based ratiometric nanoprobe for evaluating in-vivo hepatotoxicity induced by herbal medicine via MSOT imaging.

Herbal medicines are widely used around the world, while some of them are associated with adverse effects like herb-induced liver injury due to oxidative/nitrosative stress resulted from hepatically-generated ROS/RNS. It is of significance to accurately evaluate herbal-medicine-induced hepatotoxicity, since it would help provide effective monitoring method of the safety of herbal remedies. Herein we designed a ratiometric nanoprobe for in vivo imaging hepatic injury induced by herbal medicine (polygonum multiflorum, PM) via specifically responding to NO generated in liver by PM, and with MSOT imaging the precise location of liver injury can be identified. The liposomal nanoprobe consists of a responsive dye (IX-2NH2) which could specifically respond to NO and the diketopyrrolopyrrole-based conjugated polymer (DPP-TT) as the internal reference. Thus we can realize ratiometric optoacoustic detection of herbal-medicine-induced liver injury with 3D information in mouse model in a noninvasive way.

Polymer micelle with pH-triggered hydrophobic-hydrophilic transition and de-cross-linking process in the core and its application for targeted anticancer drug delivery.

In this study, an novel amphiphilic block copolymer P[PEGMA-b-(DEMA-co-APMA)]-FA and its cross-linker uracil-(CH2)6-uracil (U-(CH2)6-U) were synthesized and used as the targeted and pH-responsive nanocarriers for anticancer drug delivery. The hydrophobic block of the copolymer contains adenine (A) and tertiary amine moieties and the hydrophilic block is terminated with a targeting ligand folic acid (FA). Under neutral pH, the hydrophobic chain segments of the copolymer are cross-linked by U-(CH2)6-U through the A-U nucleobase pairing based on complementary multiple hydrogen bonding, and the copolymer forms stable micelles with their mean diameter of around 170 nm in water. While under acidic pH, the micelles dissociate as a result of protonation of tertiary amines and disruption of the A-U nucleobase pairing. Flow cytometry and fluorescent microscope observation show that, when loaded with an anticancer drug DOX, the micelles can preferably enter folate receptor (FR)-positive cancer cells and kill the cells via intracellular release of the anticancer drug. Cytotoxicity tests (MTT tests) indicate that the micelles with FA on their surfaces exhibit higher cytotoxicity toward FR-positive cells than those without FA. This study provides useful insights on designing and improving the applicability of copolymer micelles for other targeted drug delivery systems.