Background Contrast-enhanced ultrasound imaging has been widely used in the ultrasound diagnosis of a variety of tumours with high diagnostic accuracy, especially in patients with hepatic carcinoma, while its application is rarely reported in thyroid cancer. The currently used ultrasound contrast agents, microbubbles, cannot be targeted to molecular markers expressed in tumour cells due to their big size, leading to a big challenge for ultrasound molecular imaging. Phase-changeable perfluorocarbon nanoparticles may resolve the penetrability limitation of microbubbles and serve as a promising probe for ultrasound molecular imaging. Methods 65 thyroid tumour samples and 40 normal samples adjacent to thyroid cancers were determined for SHP2 expression by IHC. SHP2-targeted PLGA nanoparticles (NPs-SHP2) encapsulating perfluoropentane (PFP) were prepared with PLGA-PEG as a shell material, and their specific target-binding ability was assessed in vitro and in vivo, and the effect on the enhancement of ultrasonic imaging induced by LIFU was studied in vivo. Results In the present study, we verified that tumour overexpression of SHP2 and other protein tyrosine phosphatases regulated several cellular processes and contributed to tumorigenesis, which could be introduced to ultrasound molecular imaging for differentiating normal from malignant thyroid diagnostic nodes. The IHC test showed remarkably high expression of SHP2 in human thyroid carcinoma specimens. In thyroid tumour xenografts in mice, the imaging signal was significantly enhanced by SHP2-targeted nanoparticles after LIFU induction. Conclusion This study provides a basis for preclinical exploration of ultrasound molecular imaging with NPs-SHP2 for clinical thyroid nodule detection to enhance diagnostic accuracy.

Immunotherapy is gradually becoming as important as traditional therapy in the treatment of cancer, but adverse drug reactions limit patient benefits from PD1/PD-L1 checkpoint inhibitor drugs in the treatment of non-small cell lung cancer (NSCLC). As a chemotherapeutic drug for NSCLC, docetaxel (DTX) can synergize with PD1/PD-L1 checkpoint inhibitors but increase haematoxicity and neurotoxicity. Herein, anti-PD-L1 monoclonal antibody (mAb)-conjugated and docetaxel-loaded multifunctional lipid-shelled microbubbles (PDMs), which were designed with biologically safe phospholipids to produce synergistic antitumour effects, reduced the incidence of side effects and promoted therapeutic effects under ultrasound (US) irradiation. The PDMs were prepared by the acoustic-vibration method and then conjugated with an anti-PD-L1 mAb. The material features of the microbubbles and their cytotoxic effects, cellular apoptosis and cell cycle inhibition were studied. A subcutaneous tumour model was established to test the drug concentration-dependent and antitumour effects of the PDMs combined with US irradiation, and an orthotopic lung tumour model simultaneously confirmed the antitumour effect of this synergistic treatment. The PDMs achieved higher cellular uptake than free DTX, especially when combined with US irradiation. The PDMs combined with US irradiation also induced an increased rate of cellular apoptosis and an elevated G2-M arrest rate in cancer cells, which was positively correlated with PD-L1 expression. An in vivo study showed that synergistic treatment had relatively strong effects on tumour growth inhibition, increased survival time and decreased adverse effect rates. Our study possibly provides a well-controlled design for immunotherapy and chemotherapy and has promising potential for clinical application in NSCLC treatment. † Electronic supplementary information (ESI) available: Supplemental results and methods are depicted in the ESI Table S1: Characteristics of different microbubbles. Table S2: Encapsulation efficiency and drug-loading efficiency of microbubbles. Fig. S1: Haemolysis tests of BMs, DMs, and PDMs. Fig. S2: Mouse body weight (A) as well as AST (B), ALT (C), creatinine (D) and blood urea nitrogen (E) levels were monitored over the course of treatment. Fig. S3: HE assessment of the heart, liver, lungs, spleen, and kidneys. Fig. S4: Flow cytometry assay of C6 uptake by LLC cells treated with different formulations. ESI Fig. S5: Flow cytometry analysis of CD4 + and CD8 + TIL numbers after treatments. Fig. S6: LLC cells with Matrigel were injected into the right lung of C57BL/6 mice under X-ray guidance to establish an orthotopic tumour model. See

Iodine-125 (125 I) seed brachytherapy has been proven to be a safe and effective treatment for advanced esophageal cancer; however, the mechanisms underlying its actions are not completely understood. In the present study, the anti-cancer mechanisms of 125 I seed radiation in human esophageal squamous cell carcinoma (ESCC) cells (Eca-109 and KYSE-150) were determined, with a particular focus on the mode of cell death. The results showed that 125 I seed radiation significantly inhibited cell proliferation, and induced DNA damage and G2/M cell cycle arrest in both ESCC cell lines. 125 I seed radiation induced cell death through both apoptosis and paraptosis. Eca-109 cells were primarily killed by inducing caspase-dependent apoptosis, with 6 Gy radiation resulting in the largest response. KYSE-150 cells were primarily killed by inducing paraptosis, which is characterized by extensive cytoplasmic vacuolation. 125 I seed radiation induced autophagic flux in both ESCC cell lines, and autophagy inhibition by 3-methyladenine enhanced radiosensitivity. Furthermore 125 I seed radiation induced increased production of reactive oxygen species (ROS) in both ESCC cell lines. Treatment with an ROS scavenger significantly attenuated the effects of 125 I seed radiation on endoplasmic reticulum stress, autophagy, apoptosis, paraptotic vacuoles and reduced cell viability. In vivo experiments showed that 125 I seed brachytherapy induced ROS generation, initiated cell apoptosis and potential paraptosis, and inhibited cell proliferation and tumor growth. In summary, the results demonstrate that in ESCC cells, 125 I seed radiation induces cell death through both apoptosis and paraptosis; and at the same time initiates protective autophagy. Additionally, 125 I seed radiation-induced apoptosis, paraptosis and autophagy was considerably mediated by ROS.

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BackgroundMolecular imaging has generated a great demand to develop targeted contrast agents for MR imaging.Materials and methodsIn this study, we synthesized Src homology 2-containing phosphotyrosine phosphatase 2 (SHP2)-targeted and polylactic-co-glycolic acid–-based nanoparticles (NPs), which encapsulated perfluoropentane and being chelated with gadolinium (Gd3+) as an efficient molecular probe for targeting MR imaging on thyroid carcinoma.ResultsThese NPs displayed practical properties and favorable biocompatibility in vitro. Furthermore, they showed abilities to specifically target thyroid cancer and enhance MRI as a contrast agent in both in vitro and in vivo experiments.ConclusionThis novel MR molecular imaging based on this SHP2-targeted contrast agent provides a useful and non-invasive method for the early detection of thyroid carcinoma.