NET-targeted nanoparticles for antithrombotic therapy in pregnancy.

Pulmonary embolism caused by deep vein thrombosis (DVT) is a major contributor to maternal morbidity and mortality. There is still an unmet need for safe and effective treatment options for DVT during pregnancy. Recent research has shown that neutrophil extracellular trap (NET) formation plays a very vital role in thrombosis. We created nanoparticles surface-modified by neutrophil elastase (NE)-binding peptide that can target activated neutrophils specifically in vitro and in vivo. Prussian blue nanoparticles (PB NPs) designed in the core scavenges abnormally elevated reactive oxygen species (ROS) in the vascular microenvironment and acts as a photothermal agent to mediate photothermal therapy (PTT) to damage fibrin network structure. Based on the data we have included, this noninvasive therapeutic approach is considered safe for both mothers and the fetus. Furthermore, our findings indicate that this therapeutic approach has a significant alleviation effect on intrauterine growth restriction caused by maternal thrombosis.

Platelet membrane encapsulated curcumin nanomaterial-mediated specific thrombolysis and anti-thrombotic treatment among pregnant women.

The current treatment for venous thrombosis during pregnancy is ineffective, primarily, due to the unique physiology of pregnant women. Most clinical medications have fetal side effects when they circulate in the body. We first synthesized nanomaterials (Cur-PFP@PC) using poly lactic-co-glycolic acid (PLGA) as the base material, with curcumin (Cur) and perfluoropentane (PFP) as core components. Subsequently, we encapsulated Cur-PFP@PC into the platelet membrane to synthesize P-Cur-PFP@PC. Under ultrasound guidance, in combination with low-intensity focused ultrasound (LIFU), PFP underwent a phase change, resulting in thrombolysis. The generated microbubbles enhanced the signal impact of ultrasound, and P-Cur-PFP@PC showed better performance than Cur-PFP@PC. P-Cur-PFP@PC can target thrombosis treatment, achieve visually and precisely controlled drug release, and repair damaged blood vessels, thus avoiding the adverse effects associated with traditional long-term drug administration.

Visual resource extraction and artistic communication model design based on improved CycleGAN algorithm.

Through the application of computer vision and deep learning methodologies, real-time style transfer of images becomes achievable. This process involves the fusion of diverse artistic elements into a single image, resulting in the creation of innovative pieces of art. This article centers its focus on image style transfer within the realm of art education and introduces an ATT-CycleGAN model enriched with an attention mechanism to enhance the quality and precision of style conversion. The framework enhances the generators within CycleGAN. At first, images undergo encoder downsampling before entering the intermediate transformation model. In this intermediate transformation model, feature maps are acquired through four encoding residual blocks, which are subsequently input into an attention module. Channel attention is incorporated through multi-weight optimization achieved via global max-pooling and global average-pooling techniques. During the model's training process, transfer learning techniques are employed to improve model parameter initialization, enhancing training efficiency. Experimental results demonstrate the superior performance of the proposed model in image style transfer across various categories. In comparison to the traditional CycleGAN model, it exhibits a notable increase in structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR) metrics. Specifically, on the Places365 and selfi2anime datasets, compared with the traditional CycleGAN model, SSIM is increased by 3.19% and 1.31% respectively, and PSNR is increased by 10.16% and 5.02% respectively. These findings provide valuable algorithmic support and crucial references for future research in the fields of art education, image segmentation, and style transfer.

Low Intensity Focused Ultrasound Ignited "Deep-Penetration Nanobomb" (DPNB) for Tetramodal Imaging Guided Hypoxia-Tolerant Sonodynamic Therapy Against Hypoxic Tumors.

Background: Sonodynamic therapy (SDT) has been regarded as a novel therapeutic modality for killing tumors. However, the hypoxic tumor microenvironment, especially deep-seated tumors distant from blood vessels, severely restricts therapeutic efficacy due to the oxygen-dependent manner of SDT. Methods: Herein, we report a novel ultrasonic cavitation effect-based therapeutic modality that is able to facilitate the hypoxia-tolerant SDT for inducing hypoxic tumor death. A tLyP-1 functionalized liposomes is fabricated, composed of hematoporphyrin monomethyl ether gadolinium as the sonosentizer and perfluoropentane (PFP) as the acoustic environment regulator. Moreover, the tLyP-1 functioned liposomes could achieve active tumor homing and effective deep-penetrating into hypoxic tumors. Upon low intensity focused ultrasound (LIFU) irradiation, the acoustic droplet vaporization effect of PFP induced fast liquid-to-gas transition and quick bubbles explosion to generate hydroxyl radicals, efficiently promoting cell death in both normoxic and hypoxic microenvironment (acting as deep-penetration nanobomb, DPNB). Results: The loading of PFP is proved to significantly enhance the therapeutic efficacy of hypoxic tumors. In particular, these DPNB can also act as ultrasound, photoacoustic, magnetic resonance, and near-infrared fluorescence tetramodal imaging agents for guiding the therapeutic process. Conclusion: This study is the first report involving that liquid-to-gas transition based SDT has the potential to combat hypoxic tumors.

A multimodal imaging-guided nanoreactor for cooperative combination of tumor starvation and multiple mechanism-enhanced mild temperature phototherapy.

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has shown great promise for cancer treatment in many preclinical studies. This study reports a nanoreactor designed for an enhanced mild temperature phototherapy which utilizes multiple mechanisms including simultaneous glucose consumption, oxygen supply, glutathione (GSH) depletion and heat-resistance relief. The nanoreactor is prepared using an Fe-doped polydiaminopyridine (Fe-PDAP) nanozyme with an intrinsic catalase-like activity coloaded with glucose oxidase (GOx) and indocyanine green (ICG). Evidence shows that glucose plays a vital role in tumor progression. Initiated by the breakdown of glucose into gluconic acid and H2O2 by GOx, Fe-PDAP promotes reoxygenation by catalyzing the reaction-supplied and tumor cell-supplied H2O2 into O2, which then enhances the O2-dependent PDT. Moreover, Fe-PDAP depletes GSH in tumor cells for more efficient reactive oxygen species (ROS) production. Meanwhile, the heat resistance of tumor cells is relieved by GOx-induced glucose exhaustion and heat shock protein (HSP) reduction, improving the efficiency of PTT. In particular, the nanoreactor also serves as a contrast agent for fluorescence, photoacoustic, and magnetic resonance multimodal imaging. Consequently, this nanoreactor efficiently inhibits tumor growth through mild temperature phototherapy under multimodal imaging guidance, resulting in successful tumor ablation with minimal systemic toxicity.

Artificial Nanotargeted Cells with Stable Photothermal Performance for Multimodal Imaging-Guided Tumor-Specific Therapy.

Organic-inorganic hybrid materials have drawn increasing attention as photothermal agents in tumor therapy due to the advantages of green synthesis, high loading efficiency of hydrophobic drugs, facile incorporation of theranostic iron, and excellent photothermal efficiency without inert components or additives. Herein, we proposed a strategy for biomimetic engineering-mediated enhancement of photothermal performance in the tumor microenvironment (TME). This strategy is based on the specific characteristics of organic-inorganic hybrid materials and endows these materials with homologous targeting ability and photothermal stability in the TME. The hybrid materials perform the functions of cancer cells to target homolytic tumors (acting as "artificial nanotargeted cells (ANTC)"). Inspired by the pH-dependent disassembly behaviors of tannic acid (TA) and ferric ion (FeIII) and subsequent attenuation of photothermal performance, cancer cell membranes were self-deposited onto the surfaces of protoporphyrin-encapsulated TA and FeIII nanoparticles to achieve ANTC with TME-stable photothermal performance and tumor-specific phototherapy. The resulting ANTC can be used as contrast agents for concurrent photoacoustic imaging, magnetic resonance imaging, and photothermal imaging to guide the treatment. Importantly, the high loading efficiency of protoporphyrin enables the initiation of photodynamic therapy to enhance photothermal therapeutic efficiency, providing antitumor function with minimal side effects.

Thrombin-responsive engineered nanoexcavator with full-thickness infiltration capability for pharmaceutical-free deep venous thrombosis theranostics.

Although nanotechnology has shown great promise for treating multiple vascular diseases in recent years, simultaneous noninvasive detection and efficient dissolution of deep venous thrombosis (DVT) still remains challenging. In particular, long blockage areas and large thrombus thicknesses in DVT cause enormous difficulties for site-specific deep-seated thrombus theranostics. Therefore, based on the unique components of DVT, the novel concept of a thrombin-responsive full-thickness infiltration nonpharmaceutical nanoplatform for DVT theranostics is proposed here. The penetration depth is innovatively enhanced with efficient targeting and accumulation in the whole thrombi. Herein, we report a thrombin-responsive phase-transition liposome incorporating a liquid perfluoropentane (PFP) core and modified with two binding peptides, activatable cell-penetrating peptide (ACPP) and fibrin-binding ligand (FTP), which contribute to efficient liposome targeting and accumulation within the thrombi. This targeted nanoplatform is constructed to dig out the thrombus with the assistance of low-intensity focused ultrasound (LIFU), performing the destructive function of an excavator via an acoustic droplet vaporization effect (acting as a "nanoexcavator" system), which can activate and vaporize into microbubbles to enhance LIFU efficacy. The resulting microbubbles enable real-time monitoring of the therapeutic process with ultrasound imaging and high performance photoacoustic imaging after loading DIR. This non-invasive nonpharmaceutical thrombolytic strategy is an improvement over existing clinical methods without systemic side effects.