TiSe2-mediated sonodynamic and checkpoint blockade combined immunotherapy in hypoxic pancreatic cancer.

BACKGROUND: Pancreatic cancer remains among the most prevalent and aggressive forms of cancer. While immunotherapeutic treatment strategies have shown some promise in affected patients, the benefits of these interventions have been limited by insufficient tumor infiltration by activated T cells. RESULTS: Here, Titanium diselenide (TiSe2) nanosheets were synthesized with good stability. When exposed to ultrasound (US), the TiSe2 nanosheets served as a reliable nano-sensitizer capable of inducing large amounts of reactive oxygen species (ROS) mediating sonodynamic therapy (SDT) under hypoxic and normoxic conditions. The tumor-released TAAs induced by TiSe2 nanosheet-mediated SDT promoted immunogenic cell death (ICD) conducive to the maturation of dendritic cells (DCs), and cytokine secretion and the subsequent activation and infiltration of T cells into the tumor. Combining TiSe2-mediated SDT with anti-PD-1 immune checkpoint blockade treatment led to the efficient suppression of the growth of both primary tumor and distant tumor, while simultaneously preventing lung metastasis. These improved immunotherapeutic and anti-metastatic outcomes were associated with activated systematic antitumor immune responses, including the higher levels of DC maturation and cytokine secretion, the increased levels of CD8+ T cells and the decreased levels of Treg cells infiltrated in tumors. CONCLUSION: TiSe2 can be used as a sonosensitizer with good efficacy and high safety to mediate efficient SDT. The combination treatment strategy comprised of TiSe2-mediated SDT and PD-1 blockade activate anti-tumor immune responses effectively thorough inducing ICD, resulting in the inhibition the growth and metastasis of tumor. The combination therapy holds promise as a novel immunotherapy-based intervention strategy for pancreatic cancer patients.

Deep Penetration of Targeted Nanobubbles Enhanced Cavitation Effect on Thrombolytic Capacity.

Sonothrombolysis with microbubbles can enhance the dissolution of thrombus through the cavitation effect of microbubbles under ultrasound irradiation. However, the detailed mechanism of thrombolysis with microscaled or nanoscaled bubbles is still not so clear. This study compared the thrombolytic capacity of cRGD-targeted or nontargeted bubbles with different particle sizes combined with urokinase (UK). The size of the microscaled bubbles (Mbs or Mbs-cRGD) was mostly approximately 3 µm, while the nanoscaled bubbles (Nbs or Nbs-cRGD) were mainly around 220 nm. In vitro testing was performed on an extracorporeal circulation device that mimics human vascular thromboembolism. The rabbit clots in Mbs with UK groups showed peripheral worm-like dissolution, while the clots in Nbs with UK groups showed internal fissure-like collapse. In addition, the thrombolysis rate of Nbs-cRGD with the UK group was the highest. Furthermore, the scanning electron microscopic images showed that the fibrin network was the most severely damaged by the Nbs-cRGD, and most of the fibrin strands were dissolved. Especially, the Nbs-cRGD can penetrate much deeper than Mbs-cRGD into the thrombus and loosen the fibrin network. Taken together, benefiting from the specific identification and deep penetration to thrombus, our developed novel targeted Nbs may have broad application prospects in the clinic.

Ultrasonographic and pathological features of sclerosing stromal tumor: a case report.

Background: We herein report a rare case of a sclerosing stromal tumor (SST) in an adolescent. In this case, the mass displayed a shrinking trend, combined with its ultrasonic manifestations and pathological characteristics and may provide some references for the selection and timing of treatment, to avoid excessive harm to patients. Case Description: A healthy 17-year-old adolescent female presented to the outpatient department, complaining of abnormal uterine bleeding, but no abdominal pain, bloating, chills, or fever. The patient had no history of malignant tumors, and no relevant family or genetic history. An ultrasound showed an inhomogeneous hypoechoic area (106 mm × 53 mm × 68 mm) in the right ovarian, a clear boundary, an anechoic area inside and blood flow was observed in the mass. At a follow-up regular re-examination, the mass displayed a shrinking trend from 95 mm × 50 mm × 88 mm, 61 mm × 28 mm × 42 mm, 43 mm × 28 mm × 40 mm, 43 mm × 28 mm × 40 mm, to 42 mm × 23 mm × 28 mm. The patient underwent laparoscopic surgery a week later. Based on the immunohistochemistry and morphology results, the posterior ovarian mass was diagnosed as an SST. At one month after operation, there was no obvious abnormality on ultrasound. Conclusions: The incidence of SST is relatively low. However, due to the low specificity of clinical manifestations, imaging examination and serum tumor markers, the diagnosis of SST mainly relies on pathological examination. Therefore, in clinical practice, the possibility of misdiagnosis is greater, and attention should be paid to the differentiation of ovarian malignant tumors. Surgical resection is recommended, and the effect is good. Surgical methods should be selected individually according to the size of the tumor and the age of the patient.

Active targeting nano-scale bubbles enhanced ultrasound cavitation chemotherapy in Y1 receptor-overexpressed breast cancer.

Ultrasound cavitation therapy has attracted much attention in recent years because the cavitation of microbubbles can be leveraged to boost the infiltration of chemotherapeutic drugs into cancer tissues. For breast cancer therapy, most of the previously reported microbubbles lack specific targeting capacity and permeability. In this study, we have successfully fabricated Y1 receptor ligand (NPY)-modified bubbles, and examined their therapeutic efficacies as size-dependent functions with or without NPY targeting. To achieve this, four types of micro-scale bubbles (MBs or MBs-NPY) and nano-scale bubbles (NBs or NBs-NPY) were comprehensively evaluated. In vivo results indicated that the NBs-NPY group with doxorubicin (DOX) under ultrasound irradiation showed a high tumor suppression effect and a prolonged survival time. Furthermore, the NBs-NPY with DOX group exhibited minimal damage to mouse vital organs, which points to the considerable tolerance of the proposed nanosystem for efficacious breast cancer therapy. In summary, these findings suggest that the developed NPY-targeted NBs could have a broad application prospect in ultrasound cavitation chemotherapy of Y1 receptor-overexpressed breast cancer.