Recent Advances in Interventional Fluorescence Imaging: Toward the Precise Visualization of Transarterial Mini-Invasive Delivery Systems

CONSPECTUS:Interventional fluorescence imaging has gradually developed into a promising imaging strategy for the diagnosis of diseases in clinic.This strategy could benefit interventional targeted treatment because of the clear display of microstructures at the margins and boundaries.There are some stranded crucial issues in clinical application:(i)fast clearance of fluorescence probes;(ii)light instability and photobleaching;and(iii)residual and microsatellite lesions.The development of superstable homoge-neous intermixed formulation technology(SHIFT)can solve the aforementioned clinical problems for precision hepatectomy.Interventional fluorescence imaging based on SHIFT-prepared product has some advantages such as(i)strong stability,(ii)greatly extending imageable time window,and(iii)precisely visualizing microsatellite lesions.In this Account,we overview our current progress in interventional fluorescence imaging based on SHIFT method for surgical resection following long-lasting embolization conversion.To greatly realize interventional fluorescence imaging,we summarize clinical and preclinical application of interventional fluorescence imaging in a transarterial delivery system.Indeed,compared with conventional fluorescence imaging,interventional fluorescence imaging possesses non-negligible strengths on improved intensity in target location and step-down systemic toxicity.Unfortunately,a challenging issue is that immobile fluorescence performance is difficult to maintain after long-time embolization,resulting in a failed hepatectomy.On this basis,associated with our previous research,SHIFT was proposed and developed.Thus,we detailedly introduce and account the development and preponderance of SHIFT on interventional fluorescence imaging.Predictably,after lengthy embolization,its lightful fluorescence was still observable in tumor targets of a clinical trial.To regulate the fluorescence rendering of microsatellite lesion,SHIFT combining with pure nanoprobes(nanoICG)occurs,namely SHIFT nanoICG,and we dwell on its performance in transarterial invasive surgical navigation and its clinical application under interventional fluorescence imaging compared with conventional indocyanine green(ICG)formulations.Amazingly,the SHIFT nanoICG brings us an extraordinary imaging consequence for deep-seated tumor tissues and imperceptible microsatellite lesions.Finally,we offer perspectives on the future tendency of interventional imaging-guided SHIFT products in clinical translation such as chemoembolization,radioembolization,and immunotherapy.Actually,these directions have been underway for some time,and even relative products are already applied for clinical trials,exhibiting effective therapeutic outcomes.Our green high-performance SHIFT products are concentrated on meeting clinical needs and solving clinical problems,breaking through the cure limitations of patients with advanced diseases.Thus,the discovery offers insight into the development and superiority of SHIFT products under interventional fluorescence imaging and simultaneously provides a new view on the development of clinically pragmatic products.

The characteristics of the structure, strain and kinematic vorticity of the Wulian detachment fault zone, Shandong Peninsula, China

As one of the vital tectonic units of the Wulian Metamorphic Core Complex(MCC), the Wulian detachment fault zone(WDFZ), which developed in the Jiaodong peninsula, separates the lower plate of the ultrahigh pressure(UHP) metamorphic rocks in the Sulu orogenic belt from the upper plate of the early Cretaceous Zhucheng basin and the basin basement. The fault zone generally strikes NNE with a dip in the west along the southern portion of the MCC and strikes NE with a dip in the WNWalong the northern portion. The fault zone displays a wavy-tile-shaped extension on the plane, principally composed of the fault breccias and mylonite and transits downward to the mylonitic gneiss. As a whole, the detachment fault zone shows a top-towest or a WNW extension. By calculating the harmonic mean, we obtain a Flynn index K of 0.98–2.0, and the mean value is approximately 1.35 in the fault zone. According to the polar Mohr construction, the extensional crenulation cleavage, the RS/θ,and the quartz C-axial fabric methods, we acquire mean kinematic vorticity values of 0.64–0.97, 0.76–0.93, 0.6–0.92, and 0.63–0.98 with mean values of 0.83, 0.80, 0.78 and 0.86, respectively, for mylonite and promylonite. The strain measurement results and the kinematic vorticity values indicate that the WDFZ is a normal ductile shear zone developed in the extensional setting.The kinematic track shows that the kinematic vorticity value decreases gradually from the NW to the SE as a whole. A simple shear dominates in the middle and upper parts of the shear zone, which is reflected by a higher vorticity value(>0.75, up to 0.98),a low thinning rate and a lower K value. In contrast, toward the footwall, the pure shear is increased significantly, showing a lower vorticity value(<0.70, low to 0.64), a relatively high thinning rate and a higher K value. Combined with the geotectonic background, the development and evolution of the WDFZ should respond to lithospheric thinning and the destruction of the North China Craton(NCC). As a result, the WDFZ can be defined as a thinning normal shear zone developed in the extension tectonic setting and the combined result of the simple shear caused by the crust extension and pure shear led by the rapid uplift of the footwall and magmatic upwelling.

Bioresponsive immune-booster-based prodrug nanogel for cancer immunotherapy

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death(ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment(ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin(DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels(DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful antitumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Mulberry Biomass-Derived Nanomedicines Mitigate Colitis through Improved Inflamed Mucosa Accumulation and Intestinal Microenvironment Modulation

The therapeutic outcomes of conventional oral medications against ulcerative colitis(UC)are restricted by inefficient drug delivery to the colitis mucosa and weak capacity to modulate the inflammatory microenvironment.Herein,a fluorinated pluronic(FP127)was synthesized and employed to functionalize the surface of mulberry leaf-derived nanoparticles(MLNs)loading with resveratrol nanocrystals(RNs).The obtained FP127@RN-MLNs possessed exosome-like morphologies,desirable particle sizes(around 171.4 nm),and negatively charged surfaces(−14.8 mV).The introduction of FP127 to RN-MLNs greatly improved their stability in the colon and promoted their mucus infiltration and mucosal penetration capacities due to the unique fluorine effect.