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Trastuzumab combined with chemotherapy is the first-line treatment for advanced HER2-positive gastric cancer, but it still suffers from limited therapeutic efficiency and serious side effects, which are usually due to the poor delivery efficiency and the drug resistance of tumor cells to the chemotherapeutic drugs. Herein, a type of ultrasound microbubble for simultaneous delivery of sonosensitizers and therapeutic antibodies to achieve targeting combination of sonodynamic therapy and antibody therapy of HER2-positive gastric cancer was constructed from pyropheophorbide-lipid followed by trastuzumab conjugation (TP MBs).

Ultrasound is widely used in biomedical engineering and has applications in conventional diagnosis and drug delivery. Recent advances in ultrasound-induced drug delivery have been summarized previously in several reviews that have primarily focused on the fabrication of drug delivery carriers. This review discusses the mechanisms underlying ultrasound-induced drug delivery and factors affecting delivery efficiency, including the characteristics of drug delivery carriers and ultrasound parameters. Firstly, biophysical effects induced by ultrasound, namely thermal effects, cavitation effects, and acoustic radiation forces, are illustrated. Secondly, the use of these biophysical effects to enhance drug delivery by affecting drug carriers and corresponding tissues is clarified in detail. Thirdly, recent advances in ultrasound-triggered drug delivery are detailed. Safety issues and optimization strategies to improve therapeutic outcomes and reduce side effects are summarized. Finally, current progress and future directions are discussed.

Hypoxia in a solid tumor microenvironment (TME) can lead to the overexpression of hypoxia-inducible factor-1α (HIF-1α), which correlates to tumor metastasis. Reactive oxygen species (ROS) induced tumor cell apoptosis is becoming a promising method in tumor treatment. Currently, the ROS generating systems, e.g., photodynamic treatment and sonodynamic treatment, highly depend on oxygen (Osub2/sub) in the tumor microenvironment (TME). However, the level of Osub2/subin TME is too low to produce enough ROS. Herein, we developed an ultrasmall DSPE-PEGsub2000/subcoated barium titanate nanoparticle (P-BTO) for tumor treatment based on ultrasound triggered piezocatalysis and water splitting. Interestingly, irradiated by ultrasound, the surface of ultasmall P-BTO nanoparticles produced imbalance charges, which induced a cascade of redox reaction processes to simultaneously generate ROS and Osub2/sub, the latter one was hardly generated in large-sized barium titanate nanoparticles. The as-synthesized P-BTO reached the highest accumulation in the tumor site at 4 h after intravenous injection. The results showed that the produced Osub2/subsignificantly alleviated the hypoxia of TME to down-regulate the expression of HIF-1α, and the produced ROS can efficiently kill tumor cells. Moreover, the tumor metastasis was also inhibited, providing a different way to treat triple-negative breast cancer, which was easily metastatic and lacked effective treatments in the clinic.

As an alternative to photodynamic therapy (PDT), ultrasound-triggered tumor sonodynamic therapy (SDT) has garnered significant attention, owing to its high tissue penetration, few side effects, and reliable patient compliance. A sonosensitizer is the most important component in SDT, and high-quantum-yield safe sonosensitizers are crucial for SDT. Existing sonosensitizers mainly include organic sonosensitizers and inorganic sonosensitizers. Organic sonosensitizers, mainly some small dye molecules, have been widely studied. However, organic sonosensitizers have limited utility owing to their poor stability, rapid blood clearance, and potential phototoxicity. In contrast, inorganic sonosensitizers have stable chemical properties, long circulation time in the blood and can effectively reduce phototoxicity. In addition to their utilization as sonosensitizers, some inorganic nanoparticles can also operate as carriers for delivering organic sonosensitizers, effectively overcoming the inherent shortcomings of organic small-molecule sonosensitizers. This review mainly focuses on inorganic nanomaterial-based SDT, the possible mechanisms of SDT, and newly developed inorganic sonosensitizers, as well as the challenges and possible solutions associated with their clinical translation are introduced.

Functional nanostructures are exploited for a variety of cutting-edge fields including plasmonics, metasurfaces, and biosensors, just to name a few. Some applications require nanostructures with uniform feature sizes while others rely on spatially varying morphologies. However, fine manipulation of the feature size over a large area remains a substantial challenge because mainstream approaches to precise nanopatterning are based on low-throughput pixel-by-pixel processing, such as those utilizing focused beams of photons, electrons, or ions. In this work, we provide a solution toward wafer-scale, arbitrary modulation of feature size distribution by introducing a lithographic portfolio combining interference lithography (IL) and grayscale-patterned secondary exposure (SE). Employed after the high-throughput IL, a SE with patterned intensity distribution spatially modulates the dimensions of photoresist nanostructures. Based on this approach, we successfully fabricated 4-inch wafer-scale nanogratings with uniform linewidths of

As a traditional treatment for papillary thyroid cancer (PTC), surgical resection of diseased tissues often brings lots of inconveniences to patients, and the tumor recurrence and metastasis are difficult to avoid. Herein, we developed a gene and photothermal combined therapy nanosystem based on a polypyrrole (Ppy)-poly(ethylene imine)-siILK nanocomplex (PPR

Soft actuators and robotics have been widely researched in recent years mainly due to their compliance to environments and safe interaction with humans. However, the need of tether and low energy efficiency of such actuators/robots has limited their practical applications. This article presents a novel tendon-driven soft actuator concept that has the property of self-pumping, called soft self-pumping actuator (SSPA) in this research. A SSPA is designed by assembling two soft pneumatic actuators (SPAs) face-to-face, whose air chambers are connected by two check valves. Actuation of the SSPA is achieved by tendons that allows precise and untethered control compared with traditional SPAs. The two chambers in the proposed actuators are precharged with air to a desired pressure to enlarge self-stiffness and to facilitate bending. When actuated, one chamber will be compressed and serve as a pump to inject its air into the other chamber, resulting in further bending of the actuator. The airflow involves energy transmission to help the intended actuation, thus improving energy efficiency. In experimental studies, differential chamber air pressure is found to reduce the force in initiating actuator bending. Experimental results have also shown that energy efficiency increase of up to 45% has been achieved compared with the same design but without air transmission. We believe that the proposed concept could lead to more novel designs of controllable and energy saving soft robots.

Hypoxia, as a typical factor in a tumor microenvironment, plays a vital role in tumor treatment resistance, tumor invasion and migration. Hypoxia inducible factor (HIF), as the vital response element of hypoxia, mediates these untoward effects through a series of downstream reactions. Cancer treatments such as photodynamic therapy (PDT), radiotherapy (RT) and chemotherapy are severely hindered by hypoxia and HIF, back, however, could be intelligently manipulated through nanocomposite materials for their great potentiality to combine different functions. Herein, we reviewed the smart strategies in emerging research studies to overcome hypoxia toward the enhancement of tumor therapy.

Axillary lymph node metastasis has always been defined as the most important prognostic factor in the treatment of early breast cancer. Ultrasound and MRI can detect only 10% of lymph node micrometastases in early breast cancer. Therefore, it is crucial to detect early breast cancer with lymph node metastasis, however, there is no current examination method for accurate diagnosis. When breast cancer presents a malignant tendency, colony stimulating factor-1 and chemokine CCL-2 absorb mononuclear cells from the surrounding environment and differentiate into M2 Tumor associated macrophages (TAM), which increase the invasion of tumor cells and further promote the development of tumors. Mannose, as a simple natural ligand, can selectively bind to TAM surface CD206 (macrophage mannose receptor, MMR). In this study, mannose was connected with near infrared dye (NIR) IR780 via disulfide bond to obtain Mannose-IR780 conjugate (MR780), which was further self-assembled into near infrared nanoprobe (MR780 NPs) with quenched fluorescence. When selectively targeting CD206 highly expressed on the surface of TAM, disulfide bond was cleaved by the glutathione enriched in the microenvironment, resulting in fluorescence recovery, thus achieving NIR fluorescence molecular imaging of TAM and diagnosis of tumor lymph node metastasis in mouse models. Our findings suggest that targeted imaging of TAM enable noninvasive and sensitive detection of metastatic lymph nodes in vivo, which is instructive for tumor therapy.

The •OH induced apoptosis is a promising strategy for tumor treatment. Many current •OH generating systems are highly dependent on H2O2 in tumor microenvironment (TME). However, the H2O2 level in the TME is not high enough to produce sufficient •OH. Herein, we develop a biomimetic nano-catalyst based on TiO2/Fe3O4 platform (designed as “FTP”) to initiate a cascade of biochemical reactions to produce •OH in TME. In this platform, the modified TiO2 acting as H2O2 adsorber can promote the concentration of H2O2 around and significantly amplify Fenton reaction efficiency of Fe3O4 to induce more cell apoptosis through •OH mediated mechanism, thereby resulting in remarkable inhibition of tumor growth. The as-synthesized FTP, with diameter of 7.20 ± 1.80 nm, could efficiently accumulate in tumor via the enhanced permeability and retention (EPR) effect and act as negative T2-weighted MRI contrast agent. The results showed that the FTP could induce a significantly higher cytotoxicity profile than naked Fe3O4 nanoparticles. More specifically, the FTP exhibited significant therapeutic performance of tumors than naked Fe3O4, TiO2, and control groups.

Known for being highly sensitive and noninvasive, ultrasound imaging using microbubble contrast agents is widely used in the clinic. To use ultrasound to image tissue beyond the vasculature, researchers have developed strategies that include nanobubbles, ultrasound contrast agents generated in situ, and gene expression of ultrasound contrast agents in situ. All of these strategies offer the capability of targeting tumor cells, intratumoral imaging tumor cells and require just a small incision or no incision. In this review, we will first describe the application of nanobubbles acting as ultrasound contrast agents. Then, we will briefly introduce the stimuli-responsive formulations to generate ultrasound contrast agents in situ. Finally, we will provide an overview of the use of state-of-the-art of gene expression of ultrasound contrast agents in situ to monitor cellular location and function inside living organisms.

In precision medicine, clinical decisions and pharmaceutical evaluations tends to be made upon parallel analysis of multiple protein biomarkers. Currently, the growing needs of high-throughput multiplex immunoassay is partially satisfied by spectrally encoded bead flow suspension arrays and other platforms, yet there is still room for progress in terms of encoding capacity, decoding accuracy, ease-of-manufacture/operation, and cost-effectiveness, for which graphical suspension arrays could make substantial contributions. Here we described a suspension array system made up of graphically encoded silica particles, an automated microplate imager and an in-house data processing program. The micro-fabricated, highly uniform planar particles provide a code space of 128-plex with further extendibility. The derived multiplex immunoassay reaches sub-picogram per milliliter sensitivity level (lowest LoD = 80 fg/ml) with wide dynamic range, as well as high precision and accuracy. The potential of clinical diagnostics was demonstrated by parallel measurement of three serum biomarkers for type 1 diabetes patients. Importantly, use of standard microplates as assay vessel extends its power to high-throughput applications, such as disease screening or drug discovery.

Wetland ecological water replenishment becomes necessary in most developing countries. A holistic water replenishment scheme considering both wetland ecosystem services and irrigation requirement is needed for river water reallocation. A framework was developed in this study to calculate wetland ecological water demand (WD), river water supply capacity (RSC) and the benefit of wetland ecological water replenishment and crop irrigation with consideration of the seasonal effects. The Xianghai wetland and the Taoerhe irrigation district (TID) were considered as the study area to investigate various wetland ecological water replenishment schemes (WRS). The results showed that the WRS, considering both wetland function and agricultural irrigation, has the highest overall benefit compared to the schemes with a single focus (either wetland or irrigation). In addition, the WRS design must consider the seasonal effect because of seasonal variation of rainfall, crop growth, and wetland plants and animals&rsquo, growth. The WRS design with consideration of seasonal effect not only increased the total value of river basin from $74.83 million to $104.02 million but also balanced the benefit between TID and wetland while meeting wetland WD. This study offers a decision-making framework of developing a holistic WRS considering benefits from multiple water users and seasonal variation.