Self-Assembly of Selenium-Doped Carbon Quantum Dots as Antioxidants for Hepatic Ischemia-Reperfusion Injury Management.

Hepatic ischemia-reperfusion injury (HIRI) is a critical complication after liver surgery that negatively affects surgical outcomes of patients with the end-stage liver-related disease. Reactive oxygen species (ROS) are responsible for the development of ischemia-reperfusion injury and eventually lead to hepatic dysfunction. Selenium-doped carbon quantum dots (Se-CQDs) with an excellent redox-responsive property can effectively scavenge ROS and protect cells from oxidation. However, the accumulation of Se-CQDs in the liver is extremely low. To address this concern, the fabrication of Se-CQDs-lecithin nanoparticles (Se-LEC NPs) is developed through self-assembly mainly driven by the noncovalent interactions. Lecithin acting as the self-assembly building block also makes a pivotal contribution to the therapeutic performance of Se-LEC NPs due to its capability to react with ROS. The fabricated Se-LEC NPs largely accumulate in the liver, effectively scavenge ROS and inhibit the release of inflammatory cytokines, thus exerting beneficial therapeutic efficacy on HIRI. This work may open a new avenue for the design of self-assembled Se-CQDs NPs for the treatment of HIRI and other ROS-related diseases.

Finely tuned Prussian blue-based nanoparticles and their application in disease treatment.

The Prussian blue (PB) based nanostructure is a mixed-valence coordination network with excellent biosafety, remarkable photothermal effect and multiple enzyme-mimicking behaviours. Compared with other nanomaterials, PB-based nanoparticles (NPs) exhibit several unparalleled advantages in biomedical applications. This review begins with the chemical composition and physicochemical properties of PB-based NPs. The tuning strategies of PB-based NPs and their biomedical properties are systemically demonstrated. Afterwards, the biomedical applications of PB-based NPs are comprehensively recounted, mainly focusing on treatment of tumors, bacterial infection and inflammatory diseases. Finally, the challenges and future prospects of PB-based NPs and their application in disease treatment are discussed.

Gadolinium Metallofullerene-Polypyrrole Nanoparticles for Activatable Dual-Modal Imaging-Guided Photothermal Therapy.

Accurate diagnosis of tumor is promising to guide photothermal therapy (PTT) for efficacious tumor ablation with minimal damage to healthy tissues. Here, we report an activatable dual-modal imaging agent, which is based on PEGylated-gadolinium metallofullerene-polypyrrole nanoparticle (PEG-GMF-PPy NP) for imaging-guided PTT. A contrast agent (gadolinium metallofullerene, GMF) with excellent magnetic resonance imaging (MRI) performance and an ultra-pH-responsive polymer (PEG-PC7A) are successively modified to the surface of photothermal agent (PPy NP). The prepared PEG-GMF-PPy NPs show strong absorption in the near-infrared (NIR) region, so they can be utilized for photoacoustic imaging. Furthermore, in a tumor extracellular environment, the PEG-GMF-PPy NPs can achieve pH-enhanced MRI because of the hydrophobic-to-hydrophilic conversion of the PC7A. Upon accurate diagnosis-guided NIR laser irradiation, excellent tumor ablation effect is achieved. The results suggest that the PEG-GMF-PPy NPs are promising agents for activatable imaging-guided PTT.

Glutathione-Responsive Self-Assembled Magnetic Gold Nanowreath for Enhanced Tumor Imaging and Imaging-Guided Photothermal Therapy.

Designing nanomaterials with advanced functions and physical properties to improve cancer diagnosis and treatment has been an enormous challenge. In this work, we report the synthesis of magnetic gold nanowreaths (AuNWs) by combining wet-chemical synthesis with layer-by-layer self-assembly. The presence of Au branches, small junctions, and central holes in AuNWs led to improved photothermal effect compared with Au nanoring seeds and thick Au nanoring with smooth surface. The self-assembly of exceedingly small magnetic iron oxide nanoparticles (ES-MIONs) on the surfaces of AuNWs not only effectively quenched the T1-weighted magnetic resonance imaging (MRI) ability due to the enhanced T2 decaying effect but also provided the responsiveness to glutathione (GSH). After intravenous injection, the T1 signal of magnetic AuNWs initially in the "OFF" state can be intelligently switched on in response to the relatively high GSH concentration in tumor, and the formation of larger assemblies of ES-MIONs improved their tumor delivery compared to ES-MIONs themselves. Thus, the magnetic AuNWs showed higher MRI contrast than ES-MIONs or commercial Magnevist in T1-weighted MR imaging of tumor. Furthermore, the magnetic AuNWs have absorption in near-infrared range, leading to strong photoacoustic signal and effective photoablation of tumor. Therefore, our GSH-responsive self-assembled magnetic AuNWs could enhance T1-weighted MRI and photoacoustic imaging of tumor and be used for imaging-guided photothermal therapy.

Organic Semiconducting Photoacoustic Nanodroplets for Laser-Activatable Ultrasound Imaging and Combinational Cancer Therapy.

Combination of photoacoustic (PA) and ultrasound (US) imaging offers high spatial resolution images with deep tissue penetration, which shows great potential in applications in medical imaging. Development of PA/US dual-contrast agents with high contrast and excellent biocompatibility is of great interest. Herein, an organic semiconducting photoacoustic nanodroplet, PS-PDI-PAnD, is developed by stabilizing low-boiling-point perfluorocarbon (PFC) droplet with a photoabsorber and photoacoustic agent of perylene diimide (PDI) molecules and coencapsulating the droplet with photosensitizers of ZnF16Pc molecules. Upon irradiation, the PDI acts as an efficient photoabsorber to trigger the liquid-to-gas phase transition of the PFC, resulting in dual-modal PA/US imaging contrast as well as photothermal heating. On the other hand, PFC can serve as an O2 reservoir to overcome the hypoxia-associated resistance in cancer therapies, especially in photodynamic therapy. The encapsulated photosensitizers will benefit from the sustained oxygen release from the PFC, leading to promoted photodynamic efficacy regardless of pre-existing hypoxia in the tumors. When intravenously injected into tumor-bearing mice, the PS-PDI-PAnDs show a high tumor accumulation via EPR effect. With a single 671 nm laser irradiation, the PS-PDI-PAnDs exhibit a dual-modal PA/US imaging-guided synergistic photothermal and oxygen self-enriched photodynamic treatment, resulting in complete tumor eradication and minimal side effects. The PS-PDI-PAnDs represents a type of PFC nanodroplets for synergistic PDT/PTT treatment upon a single laser irradiation, which is expected to hold great potential in the clinical translation in dual-modal PA/US imaging-guided combinational cancer therapy.

Suppressing Nanoparticle-Mononuclear Phagocyte System Interactions of Two-Dimensional Gold Nanorings for Improved Tumor Accumulation and Photothermal Ablation of Tumors.

The clearance of nanoparticles (NPs) by mononuclear phagocyte system (MPS) from blood leads to high liver and spleen uptake and negatively impacts their tumor delivery efficiency. Here we systematically evaluated the in vitro and in vivo nanobio interactions of a two-dimensional (2D) model, gold (Au) nanorings, which were compared with Au nanospheres and Au nanoplates of similar size. Among different shapes, Au nanorings achieved the lowest MPS uptake and highest tumor accumulation. Among different sizes, 50 nm Au nanorings showed the highest tumor delivery efficiency. In addition, we demonstrated the potential use of Au naonrings in photoacoustic imaging and photothermal therapy. Thus, engineering the shape, surface area, and size of Au nanostructures is important in controlling NP-MPS interactions and improving the tumor uptake efficiency.

Self-Assembly of Semiconducting-Plasmonic Gold Nanoparticles with Enhanced Optical Property for Photoacoustic Imaging and Photothermal Therapy.

Although various noble metal and semiconducting molecules have been developed as photoacoustic (PA) agents, the use of semiconducting polymer-metal nanoparticle hybrid materials to enhance PA signal has not been explored. A novel semiconducting-plasmonic nanovesicle was fabricated by self-assembly of semiconducting poly(perylene diimide) (PPDI) and poly(ethylene glycol (PEG) tethered gold nanoparticles (Au@PPDI/PEG). A highly localized and strongly enhanced electromagnetic (EM) field is distributed between adjacent gold nanoparticles in the vesicular shell, where the absorbing collapsed PPDI is present. Significantly, the EM field in turn enhances the light absorption efficiency of PPDI, leading to a much greater photothermal effect and a stronger photoacoustic signal compared to PDI nanoparticle or gold nanovesicle alone. The optical property of the hybrid vesicle can be further tailored by controlling the ratio of PPDI and gold nanoparticle as well as the adjustable interparticle distance of gold nanoparticles localized in the vesicular shell. In vivo imaging and therapeutic evaluation demonstrated that the hybrid vesicle is an excellent probe for cancer theranostics.

Rational Design of Branched Nanoporous Gold Nanoshells with Enhanced Physico-Optical Properties for Optical Imaging and Cancer Therapy.

Reported procedures on the synthesis of gold nanoshells with smooth surfaces have merely demonstrated efficient control of shell thickness and particle size, yet no branch and nanoporous features on the nanoshell have been implemented to date. Herein, we demonstrate the ability to control the roughness and nanoscale porosity of gold nanoshells by using redox-active polymer poly(vinylphenol)-b-(styrene) nanoparticles as reducing agent and template. The porosity and size of the branches on this branched nanoporous gold nanoshell (BAuNSP) material can be facilely adjusted by control of the reaction speed or the reaction time between the redox-active polymer nanoparticles and gold ions (Au3+). Due to the strong reduction ability of the redox-active polymer, the yield of BAuNSP was virtually 100%. By taking advantage of the sharp branches and nanoporous features, BAuNSP exhibited greatly enhanced physico-optical properties, including photothermal effect, surface-enhanced Raman scattering (SERS), and photoacoustic (PA) signals. The photothermal conversion efficiency can reach as high as 75.5%, which is greater than most gold nanocrystals. Furthermore, the nanoporous nature of the shells allows for effective drug loading and controlled drug release. The thermoresponsive polymer coated on the BAuNSP surface serves as a gate keeper, governing the drug release behavior through photothermal heating. Positron emission tomography imaging demonstrated a high passive tumor accumulation of 64Cu-labeled BAuNSP. The strong SERS signal generated by the SERS-active BAuNSP in vivo, accompanied by enhanced PA signals in the tumor region, provide significant tumor information, including size, morphology, position, and boundaries between tumor and healthy tissues. In vivo tumor therapy experiments demonstrated a highly synergistic chemo-photothermal therapy effect of drug-loaded BAuNSPs, guided by three modes of optical imaging.

A pillararene-based ternary drug-delivery system with photocontrolled anticancer drug release.

A novel ternary drug delivery system (DDS) is constructed using a photodegradable anticancer prodrug (Py-Cbl), a water-soluble pillararene supramolecular container (WP6), and the diblock copolymer methoxy-poly(ethylene glycol)114 -block-poly(L -lysine hydrochloride)200. This DDS successfully addresses three important issues: enhancement of the water solubility of the anticancer prodrug; controlled release of the anticancer drug; accurate and quantitative measurement of the drug release.