Background/Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor with limited therapeutic options despite multimodal treatment. Small interfering RNA (siRNA)-based therapeutics can silence tumor-promoting genes, but achieving efficient and tumor-specific delivery remains challenging. Lipid nanoparticles (LNPs) are promising siRNA carriers; however, conventional antibody conjugation can impair antigen recognition and complicate manufacturing. This study aimed to establish a modular Fc-binding peptide (FcBP)-mediated post-insertion strategy to enable PD-L1-targeted delivery of VEGF-siRNA via LNPs for GBM therapy. Methods: Preformed VEGF-siRNA-loaded LNPs were functionalized with FcBP–lipid conjugates, enabling non-covalent anchoring of anti-PD-L1 antibodies through Fc interactions. Particle characteristics were analyzed using dynamic light scattering and encapsulation efficiency assays. Targeted cellular uptake and VEGF gene silencing were evaluated in PD-L1-positive GL261 glioma cells. Anti-tumor efficacy was assessed in a subcutaneous GL261 tumor model following repeated intratumoral administration using tumor volume and bioluminescence imaging as endpoints. Results: FcBP post-insertion preserved LNP particle size (125.2 ± 1.3 nm), polydispersity, zeta potential, and siRNA encapsulation efficiency. Anti-PD-L1–FcBP-LNPs significantly enhanced cellular uptake (by ~50-fold) and VEGF silencing in PD-L1-expressing GL261 cells compared to controls. In vivo, targeted LNPs reduced tumor volume by 65% and markedly suppressed bioluminescence signals without inducing weight loss. Final tumor weight was reduced by 63% in the anti-PD-L1–FcBP–LNP group (656.9 ± 125.4 mg) compared to the VEGF-siRNA LNP group (1794.1 ± 103.7 mg). The FcBP-modified LNPs maintained antibody orientation and binding activity, enabling rapid functionalization with targeting antibodies. Conclusions: The FcBP-mediated post-insertion strategy enables site-specific, modular antibody functionalization of LNPs without compromising physicochemical integrity or antibody recognition. PD-L1-targeted VEGF-siRNA delivery demonstrated potent, selective anti-tumor effects in GBM murine models. This platform offers a versatile approach for targeted nucleic acid therapeutics and holds translational potential for treating GBM.

Background and Objectives: Non-cystic manifestation of autosomal dominant polycystic kidney disease (ADPKD) is an important risk factor for cerebral aneurysms. In this report, we describe a rare spontaneous internal carotid artery (ICA) dissection in a patient with ADPKD. Observations: A 38-year-old woman with a history of ADPKD and acute myocardial infarction due to coronary artery dissection experienced severe spontaneous pain on the left side of her neck. Magnetic resonance imaging (MRI) revealed a severe left ICA stenosis localized at its origin. Carotid plaque MRI showed that the stenotic lesion was due to a subacute intramural hematoma. Close follow-up by an imaging study was performed under the diagnosis of spontaneous extracranial ICA dissection, and spontaneous regression of the intramural hematoma was observed uneventfully. Conclusions: When patients with a history of ADPKD present with severe neck pain, it is crucial to consider the possibility of a spontaneous ICA dissection. A carotid plaque MRI is beneficial in the differential diagnosis. Conservative management may benefit patients without ischemic symptoms.

Background/Objectives: Primary central nervous system lymphoma (PCNSL) has a markedly high proliferation rate, making early diagnosis and prompt therapeutic intervention essential. To accelerate diagnosis, our institution adopted flow cytometry (FCM) in conjunction with conventional histopathology, and this study therefore evaluated the diagnostic performance of FCM for PCNSL. Methods: We retrospectively analyzed 67 consecutive patients with suspected PCNSL who underwent intraoperative FCM between 2010 and 2023 based on preoperative imaging. B-cell clonality was defined as ≥20% CD19/CD20-positive cells with a κ/λ ratio of >3.0 or <0.5. Results: Using histopathology, we confirmed the presence of PCNSL in 42 patients, all diagnosed as having diffuse large B-cell lymphoma. Six cases (14.3%) were discordant (FCM-D). The sensitivity, specificity, and positive predictive value of FCM were 85.7%, 100%, and 100%, respectively. T-cell markers were significantly elevated in FCM-D cases (p < 0.01), although these were pathologically diagnosed as diffuse large B-cell lymphoma based on histology and immunohistochemistry. Conclusions: FCM yields reliable diagnostic information within hours of tissue collection and supports early therapeutic decisions in PCNSL. Discordant results may reflect reactive T-cell infiltration. This is the first study to present detailed subset analyses in PCNSL using FCM in correlation with pathology, underscoring its utility as a rapid diagnostic tool.

Background/Objectives: Diagnosing hemangioblastomas using magnetic resonance imaging (MRI) is challenging, especially when the tumors appear as solid posterior fossa masses. This study aimed to evaluate the diagnostic performance of perfusion MRI and identify the most useful quantitative features for differentiating hemangioblastomas from other posterior fossa tumors. Methods: Forty-five posterior fossa tumors were analyzed, including 18 hemangioblastomas (HB group) and 27 non-hemangioblastoma tumors (NHB group; 8 metastatic brain tumors, 6 pilocytic astrocytomas, 5 malignant lymphomas, 4 glioblastomas, 2 medulloblastomas, and 2 other tumors). All patients underwent 3.0-T MRI. Arterial spin labeling (ASL) was used to calculate the relative tumor blood flow normalized to the contralateral gray matter. Dynamic susceptibility contrast (DSC) imaging was used to obtain regional cerebral blood flow, regional and corrected cerebral blood volume (CBV), and permeability index (K2) values. Regions of interest (ROIs) were placed within the contrast-enhancing areas. Results: The relative ASL values and corrected CBV were significantly higher in hemangioblastomas than in other tumors (p < 0.001). Relative ASL showed the highest diagnostic performance (sensitivity, 100%; specificity, 93.3%). Conclusions: Non-contrast ASL showed strong diagnostic performance for identifying posterior fossa hemangioblastomas and may serve as a practical alternative to contrast-enhanced DSC, although ROI placement can be challenging in very small mural nodules.

Lipid nanoparticles (LNPs) have emerged as a key delivery platform for mRNA therapeutics, as demonstrated by the clinical success of mRNA vaccines against SARS-CoV-2. LNPs are now being investigated for various applications, such as cancer immunotherapy and the treatment of genetic disorders. However, LNPs tend to accumulate predominantly in the liver and lack intrinsic cell-type specificity. Modifying LNPs with antibodies is a promising strategy for enhancing cell-specific delivery. We have previously developed orientation-controlled anti-transferrin receptor and anti-PD-L1 antibody modifications for the targeted delivery of nucleic acids, including mRNA and siRNA. In this study, we newly applied this platform to trastuzumab, a clinically established high-affinity anti-HER2 therapeutic antibody, to develop orientation-controlled trastuzumab-modified mRNA/LNPs for HER2-selective delivery. we evaluated trastuzumab-modified mRNA/LNPs in HER2-overexpressing SKOV-3 ovarian cancer cells and HER2-low MDA-MB-231 breast cancer cells. Trastuzumab-modified mRNA/LNPs exhibited over 100-fold greater cellular association than unmodified LNPs in cultured HER2-overexpressing SKOV-3 cells. Furthermore, after intratumoral administration in a mouse model bearing subcutaneous SKOV-3 tumors, the trastuzumab-modified group showed significantly higher luciferase expression than the unmodified and isotype-controlled antibody-modified groups. These findings support FcBP-HFQ lipid-mediated trastuzumab modification of LNPs as a useful approach for efficient cell-selective mRNA delivery.