Enhancement of the Anti-Angiogenic Effects of Delphinidin When Encapsulated within Small Extracellular Vesicles.

(1) Background: The anthocyanin delphinidin exhibits anti-angiogenic properties both in in vitro and in vivo angiogenesis models. However, in vivo delphinidin is poorly absorbed, thus its modest bioavailability and stability reduce its anti-angiogenic effects. The present work takes advantage of small extracellular vesicle (sEV) properties to enhance both the stability and efficacy of delphinidin. When encapsulated in sEVs, delphinidin inhibits the different stages of angiogenesis on human aortic endothelial cells (HAoECs). (2) Methods: sEVs from immature dendritic cells were produced and loaded with delphinidin. A method based on UHPLC-HRMS was implemented to assess delphinidin metabolites within sEVs. Proliferation assay, nitric oxide (NO) production and Matrigel assay were evaluated in HAoECs. (3) Results: Delphinidine, 3-O-ß-rutinoside and Peonidin-3-galactoside were found both in delphinidin and delphinidin-loaded sEVs. sEV-loaded delphinidin increased the potency of free delphinidin 2-fold for endothelial proliferation, 10-fold for endothelial NO production and 100-fold for capillary-like formation. Thus, sEV-loaded delphinidin exerts effects on the different steps of angiogenesis. (4) Conclusions: sEVs may be considered as a promising approach to deliver delphinidin to target angiogenesis-related diseases, including cancer and pathologies associated with excess vascularization.

Meningeal carcinomatosis of the internal auditory meatus: clinical and imagery-aided differentiation.

OBJECTIVES: To describe difficulties in diagnosing meningeal carcinomatosis of the internal auditory meatus (IAM-MC). STUDY DESIGN: Retrospective case review. SETTING: Tertiary skull base surgery referral center. PATIENTS: A series of six cases of patients diagnosed with IAM-CM over 14 years. RESULTS: The primary cancer was known before diagnosis in three cases (adenocarcinoma of lung, breast, and melanoma). In two others, it was discovered at workup (lung, ethmoid adenocarcinoma). In the last case, no primary cancer was identified. Vestibular symptoms were the first complaint in five of the six cases. Referral symptom was facial paralysis in five cases and rapid-onset total deafness associated with severe unsteadiness in one. Rapid hearing decrease and symptoms of bilateralization were observed in five cases. Diagnosis was ascertained by discovery of malignant cells in the CSF in three cases and at tumor biopsy in one case. In the two other cases, the association of brain metastases and increased dura mater infiltration was convincing. Treatment consisted in radiation therapy to the whole brain in five cases and intrathecal chemotherapy in one case. Evolution was rapidly lethal in five cases. The last died free of disease 4 years after treatment. CONCLUSION: IAM-MC is difficult to demonstrate. Progressive facial paralysis associated with aggressive and rapidly bilateral cochlear and vestibular symptoms are highly evocative in the event of cancer in the patient's history. If there is no history of cancer, lumbar puncture is to be repeated until malignant cells are discovered in the CSF before beginning radiotherapy.