Quality inspection of micro solder joints in laser spot welding by laser ultrasonic method.

The quality inspection of micro solder joints in laser spot welding (LSW) is a problem of great concern in industrial application. In this paper, a laser ultrasonic technology (LUT) was proposed to inspect the quality of micro solder joints in LSW. Firstly, based on the thermoelastic model of acoustic wave propagation in solid, a theoretical model was built and used to analyze the propagation properties of the Lamb wave in the whole field by finite element method (FEM), the transmitting properties of the excited Lamb wave via solder joint were affected by the effective contacted area of solder joint. Secondly, LUT was used to inspect the 1.2 mm/0.4 mm welding spot of standard/false 304 stainless steel welded components. By comparing the propagating properties of excited ultrasonic wave in different samples with different weld quality, the standard and false welding can be visually distinguished. Finally, a industrial CT was used to check the quality of the samples used in our experiment. Inclusions and pores have been found in the false solder joints, which will reduce the effective contacted area of solder joint, and then affected the propagation of ultrasonic wave. By combining the CT results and the experimental analysis, the experimental results detected by LUT are in good agreement with the simulation results. So, the LUT is a potential method in field of the quality inspection of micro solder joints in LSW.

Mesenchymal Stem Cells Functionalized Sonodynamic Treatment for Improving Therapeutic Efficacy and Compliance of Orthotopic Oral Cancer.

Despite multiple treatment options being available, many critical challenges are still ongoing in the treatment of oral squamous cell carcinoma (OSCC). Particularly, the major hurdle is to avoid facial disfigurement and oral function disability during treatment. Herein, nanoengineered mesenchymal stem cells (MSCs) are developed as a supersonosensitizer, named M/LPV/O2 , for improving nondestructive sonodynamic therapy (SDT) against OSCC along with good therapeutic compliance. M/LPV/O2 is composed of an MSCs membrane functionalized liposomal formulation of oxygen-loading perfluorocarbon and sonosensitizer verteporfin (M/LPV/O2 ), which can not only increase circulation and targeting efficacy but also supply oxygen to overcome tumor-hypoxia-associated resistance in SDT, resulting in enhanced therapeutic outcomes in vitro and in vivo. It is identified that M/LPV/O2 effectively stimulates the generation of reactive oxygen species even in hypoxic conditions, and consequently tremendously induces cancer cell death. In addition, M/LPV/O2 displays good tumor accumulation and penetration under ultrasound stimulation, and efficiently induces tumor inhibition and even abrogation, leading to prolonged survival of tumor-bearing mice. Importantly, M/LPV/O2 -based SDT exhibits minimal systemic adverse effects and successfully maintains oral functions with no facial tissue damage. Therefore, these studies provide a promising therapeutic strategy for OSCC, which has a potential to enhance life quality and compliance after treatment.

Nanosized Phase-Changeable "Sonocyte" for Promoting Ultrasound Assessment.

Despite the ability of microbubble contrast agents to improve ultrasound diagnostic performance, their application potential is limited due to low stability, fast clearance, and poor tissue permeation. This study presents a promising nanosized phase-changeable erythrocyte (Sonocyte), composed of liposomal dodecafluoropentane coated with multilayered red blood cell membranes (RBCm), for improving ultrasound assessments. Sonocyte is the first RBCm-functionalized ultrasound contrast agent with uniform nanosized morphology, and exhibits good stability, systemic circulation, target-tissue accumulation, and even ultrasound-responsive phase transition, thereby satisfying the inherent requirement of ultrasound imaging. It is identified that Sonocyte displays similar sensitivity as microbubble SonoVue, a clinical ultrasound contrast agent, for effectively detecting normal parenchyma and hepatic necrosis. Importantly, compared with SonoVue lacking of ability to detect tumors, Sonocyte can identify tumors with high sensitivity and specificity due to superior tumor accumulation and penetration. Therefore, Sonocyte exhibits superior capabilities over SonoVue, endowing with a great clinical application potential.

Ultrasound-responsive alkaline nanorobots for the treatment of lactic acidosis-mediated doxorubicin resistance.

Lactic acidosis is one of the key characteristics of the tumor microenvironment (TME), and plays a critical role in therapy resistance, making it an attractive target for enhancing anticancer treatment. However, no effective systems exhibit the ability to selectively neutralize tumor lactic acidosis in a controlled manner. Here, we have developed novel ultrasound-responsive alkaline nanorobots (AN-DSP), composed of PLGA nanoparticles containing doxorubicin (DOX), sodium carbonate (Na2CO3) and perfluorocarbon (PFC), for recovering from lactic acidosis-mediated drug resistance. AN-DSP exhibit sensitive response to ultrasound stimulation, and rapidly release Na2CO3 to neutralize lactic acidosis, consequently enhancing DOX susceptibility in vitro and in vivo. Particularly, our nanorobots autonomously accumulate in tumors by an enhanced permeability and retention effect, and can specifically disrupt the tumor acidic microenvironment in response to external ultrasonic powering, resulting in the inhibition of tumor growth with minimal adverse effects. Therefore, AN-DSP represent a promising approach for selectively overcoming tumor lactic acidosis induced therapeutic resistance.

The first integrins ß3-mediated cellular and nuclear targeting therapeutics for prostate cancer.

Prostate cancer is one of the most commonly diagnosed cancers in men, leading to a high mortality rate due to a lack of effective anticancer treatment. Current anticancer chemotherapeutics are often administrated at suboptimal doses because of nonspecific toxicities to normal tissues, resulting in the eventual failure of therapy as well as the development of drug resistance and metastatic disease. Therefore, ligand-targeted therapeutics have the great potential of improving the selective anticancer toxicity. Integrins ß3 (αvß3 and αIIbß3) are an important cell adhesion molecular family, overexpressed on both cell membrane and perinuclear region of prostate cancer cells, and play a key role in the progression and metastasis of prostate cancer, making them an attractive target for anticancer therapy. However, their clinical impacts have been limited due to lack of specific ligands. Here, for the first time, we have identified a peptide Arginine-Tryptophan-(D-Arginine)-Asparagine-Arginine as an integrins ß3 specific ligand, named B3int, which shows superior selectivity to integrins ß3 over other integrin subunits. B3int has high affinity to integrins ß3 with a Kd value of 0.2 nM, which is 7-fold higher than c-RGDyK (1.4 nM), a well-established integrin αvß3 ligand. In addition, B3int shows high specificity for integrins ß3, and can selectively target integrin ß3 overexpressed cancer cells in vitro and in vivo. Most importantly, B3int-modified liposomes (B3int-LS-DOX) can selectively deliver DOX not only into prostate cancer cells, but into nucleus via targeting integrins ß3, thereby significantly improving anticancer effects in 2D prostate cancer cells and 3D tumor spheroids. Particularly, B3int-LS-DOX effectively inhibits tumor growth with an effective dose of as low as 1.5 mg/kg, which is 3.3-fold less than c-RGDyK-LS-DOX (5 mg/kg), indicating that integrins ß3 specific therapy is a promising anticancer strategy which can greatly improve the anticancer therapeutic index. In summary, we have identified B3int as the first integrins ß3 specific ligand with high affinity and specificity, and holds a great potential of improving the diagnosis and treatment for integrins ß3-overexpressed cancers.

Glutathione Induced Transformation of Partially Hollow Gold-Silver Nanocages for Cancer Diagnosis and Photothermal Therapy.

Gold-silver nanocages (GSNCs) are widely used in cancer imaging and therapy due to excellent biocompatibility, internal hollow structures, and tunable optical properties. However, their possible responses toward the tumor microenvironment are still not well understood. In this study, it is demonstrated that a kind of relatively small sized (35 nm) and partially hollow GSNCs (absorbance centered at 532 nm) can enhance the intrinsic photoacoustic imaging performances for blood vessels around tumor sites. More importantly, the high concentration of glutathione around the tumor cells' microenvironment may induce the aggregation, disintegration, and agglomeration of these GSNCs sequentially, allowing significant shifts in the absorbance spectrum of GSNCs to the near-infrared (NIR) region. This enhanced absorbance in the NIR region entails the significant photothermal therapy (PTT) effect. In vivo experiments, including photoacoustic microscopy (PAM) for cancer diagnosis and PTT in tumor model mice, also show coincident consequences. Taken together, the slightly hollow GSNCs may assist PAM-based tumor diagnosis and induce a tumor targeted PTT effect. This work paves a new avenue for the development of an alternative tumor diagnostic and therapeutic strategy.