Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme

Abstract Radiotherapy is an essential step during the treatment of glioblastoma multiforme (GBM), one of the most lethal malignancies. The survival in patients with GBM was improved by the current standard of care for GBM established in 2005 but has stagnated since then. Since GBM is a radioresistant malignancy and the most of GBM recurrences occur in the radiotherapy field, increasing the effectiveness of radiotherapy using high-Z metal nanoparticles (NPs) has recently attracted attention. This review summarizes the progress in radiotherapy approaches for the current treatment of GBM, the physical and biological mechanisms of radiosensitization through high-Z metal NPs, and the results of studies on radiosensitization in the in vitro and in vivo GBM models using high-Z metal NPs to date

Prognostic impact of an integrative analysis of [18F]FDG PET parameters and infiltrating immune cell scores in lung adenocarcinoma

Background : High levels of 18F-fluorodeoxyglucose (18F-FDG) tumor uptake are associated with worse prognosis in patients with non-small cell lung cancer (NSCLC). Meanwhile, high levels of immune cell infiltration in primary tumor have been linked to better prognosis in NSCLC. We conducted this study for precisely stratified prognosis of the lung adenocarcinoma patients using the integration of 18F-FDG positron emission tomography (PET) parameters and infiltrating immune cell scores as assessed by a genomic analysis. Results : Using an RNA sequencing dataset, the patients were divided into three subtype groups. Additionally, 24 different immune cell scores and cytolytic scores (CYT) were obtained. In 18F-FDG PET scans, PET parameters of the primary tumors were obtained. An ANOVA test, a Chi-square test and a correlation analysis were also conducted. A Kaplan–Meier survival analysis with the log-rank test and multivariable Cox regression test was performed to evaluate prognostic values of the parameters. The terminal respiratory unit (TRU) group demonstrated lower 18F-FDG PET parameters, more females, and lower stages than the other groups. Meanwhile, the proximal inflammatory (PI) group showed a significantly higher CYT score compared to the other groups (P = .001). Also, CYT showed a positive correlation with tumor-to-liver maximum standardized uptake value ratio (TLR) in the PI group (P = .027). A high TLR (P = .01) score of 18F-FDG PET parameters and a high T follicular helper cell (TFH) score (P = .005) of immune cell scores were associated with prognosis with opposite tendencies. Furthermore, TLR and TFH were predictive of overall survival even after adjusting for clinicopathologic features and others (P = .024 and .047). Conclusions : A high TLR score was found to be associated with worse prognosis, while high CD8 T cell and TFH scores predicted better prognosis in lung adenocarcinoma. Furthermore, TLR and TFH can be used to predict prognosis independently in patients with lung adenocarcinoma.This study was supported by the National Research Foundation of Korea (NRF) (NRF-2019M2D2A1A01058210, NRF-2020R1C1C1009000, 2021M2E8A1039564) and Creative-Pioneering Researchers Program through Seoul National University (SNU)

Development of theranostic dual-layered Au-liposome for effective tumor targeting and photothermal therapy

Abstract Background Photothermal therapy (PTT) is an emerging anti-cancer therapeutic strategy that generates hyperthermia to ablate cancer cells under laser irradiation. Gold (Au) coated liposome (AL) was reported as an effective PTT agent with good biocompatibility and excretory property. However, exposed Au components on liposomes can cause instability in vivo and difficulty in further functionalization. Results Herein, we developed a theranostic dual-layered nanomaterial by adding liposomal layer to AL (LAL), followed by attaching polyethylene glycol (PEG) and radiolabeling. Functionalization with PEG improves the in vivo stability of LAL, and radioisotope labeling enables in vivo imaging of LAL. Functionalized LAL is stable in physiological conditions, and 64Cu labeled LAL (64Cu-LAL) shows a sufficient blood circulation property and an effective tumor targeting ability of 16.4%ID g−1 from in vivo positron emission tomography (PET) imaging. Also, intravenously injected LAL shows higher tumor targeting, temperature elevation in vivo, and better PTT effect in orthotopic breast cancer mouse model compared to AL. The tumor growth inhibition rate of LAL was 3.9-fold higher than AL. Conclusion Based on these high stability, in vivo imaging ability, and tumor targeting efficiency, LAL could be a promising theranostic PTT agent. Graphic Abstrac

A case of nearly complete response in hepatocellular carcinoma with disseminated lung metastasis by combination therapy of nivolumab and ipilimumab after treatment failure of atezolizumab plus bevacizumab

Recently, the efficacy of immuno-oncologic agents for advanced hepatocellular carcinoma (HCC) has been proven in several trials. In particular, atezolizumab with bevacizumab (AteBeva), as a first-line therapy for advanced HCC, has shown tremendous advances in the IMBrave150 study. However, second or third-line therapy after treatment failure with AteBeva has not been firmly established. Moreover, clinicians have continued their attempts at multidisciplinary treatment that includes other systemic therapy and radiotherapy (RT). Here, we report a case that showed a near complete response (CR) of lung metastasis to nivolumab with ipilimumab therapy after achieving a near CR of intrahepatic tumor using sorafenib and RT in a patient with advanced HCC who had experienced treatment failure of AteBeva

Association of metabolic and genetic heterogeneity in head and neck squamous cell carcinoma with prognostic implications: integration of FDG PET and genomic analysis

Purpose The linkage between the genetic and phenotypic heterogeneity of the tumor has not been thoroughly evaluated. Herein, we investigated how the genetic and metabolic heterogeneity features of the tumor are associated with each other in head and neck squamous cell carcinoma (HNSC). We further assessed the prognostic significance of those features. Methods The mutant-allele tumor heterogeneity (MATH) score (n = 508), a genetic heterogeneity feature, and tumor glycolysis feature (GlycoS) (n = 503) were obtained from the HNSC dataset in the cancer genome atlas (TCGA). We identified matching patients (n = 33) who underwent 18F-fluorodeoxyglucose positron emission tomography (FDG PET) from the cancer imaging archive (TCIA) and obtained the following information from the primary tumor: metabolic, metabolic-volumetric, and metabolic heterogeneity features. The association between the genetic and metabolic features and their prognostic values were assessed. Results Tumor metabolic heterogeneity and metabolic-volumetric features showed a mild degree of association with MATH (n = 25, ρ = 0.4~0.5, P < 0.05 for all features). The patients with higher FDG PET features and MATH died sooner. Combination of MATH and tumor metabolic heterogeneity features showed a better stratification of prognosis than MATH. Also, higher MATH and GlycoS were associated with significantly worse overall survival (n = 499, P = 0.002 and 0.0001 for MATH and GlycoS, respectively). Furthermore, both MATH and GlycoS independently predicted overall survival after adjusting for clinicopathologic features and the other (P = 0.015 and 0.006, respectively). Conclusion Both tumor metabolic heterogeneity and metabolic-volumetric features assessed by FDG PET showed a mild degree of association with genetic heterogeneity in HNSC. Both metabolic and genetic heterogeneity features were predictive of survival and there was an additive prognostic value when the metabolic and genetic heterogeneity features were combined. Also, MATH and GlycoS were independent prognostic factors in HNSC; they can be used for precise prognostication once validated.This study was supported by the National Research Foundation of Korea (NRF) (NRF-2017R1D1A1B03035556, and NRF-2019M2D2A1A01058210), and the Ministry of Health and Welfare Korea (HI18C0886, and HI19C0339)

Magnetic and near-infrared derived heating characteristics of dimercaptosuccinic acid coated uniform Fe@Fe3O4 core–shell nanoparticles

Among the number of hyperthermia materials, magnetic nanoparticles have received much attention. In this work, we studied the heating characteristics of uniform Fe@Fe3O4 core–shell nanoparticle under near-infrared laser irradiation and external AC magnetic field applying. The Fe@Fe3O4 core–shell nanoparticles were prepared by thermal decomposition of iron pentacarbonyl and followed by controlled oxidation. The prepared uniform particles were further coated with dimercaptosuccinic acid to make them well dispersed in water. Near-infrared derived photothermal study of solutions containing a different concentration of the core–shell nanoparticles was made by using 808 nm laser Source. Additionally, magnetic hyperthermia ability of the Fe@Fe3O4 nanoparticle at 150 kHz and various oersted (140–180 Oe) condition was systemically characterized. The Fe@Fe3O4 nanoparticles which exhibited effective photo and magnetic hyperthermia are expected to be used in biomedical application.This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A1B07051249), Nano Material Technology Develop‑ment Program (NRF-2015M3A7B6027970) of MSIP/NRF and Center for Inte‑grated Smart Sensors funded by the Ministry of Science, ICT, and Future Plan‑ning, Republic of Korea, as Global Frontier Project (CISS-012M3A6A6054186)

Mannosylated-serum albumin nanoparticle imaging to monitor tumor-associated macrophages under anti-PD1 treatment

Background Immune checkpoint inhibitors such as anti-programmed cell death protein 1 (PD1) block tumor growth by reinvigorating the immune system; however, determining their efcacy only by the changes in tumor size may prove inaccurate. As the immune cells including macrophages in the tumor microenvironment (TME) are associ‑ ated with the response to anti-PD1 therapy, tumor-associated macrophages (TAMs) imaging using nanoparticles can noninvasively provide the immune enrichment status of TME. Herein, the mannosylated-serum albumin (MSA) nano‑ particle was labeled with radioactive isotope 68Ga to target the mannose receptors on macrophages for noninvasive monitoring of the TME according to anti-PD1 therapy. Results B16F10-Luc and MC38-Luc tumor-bearing mice were treated with anti-PD1, and the response to anti-PD1 was determined by the tumor volume. According to the fow cytometry, the responders to anti-PD1 showed an increased proportion of TAMs, as well as lymphocytes, and the most enriched immune cell population in the TME was also TAMs. For noninvasive imaging of TAMs as a surrogate of immune cell augmentation in the TME via anti-PD1, we acquired [ 68Ga] Ga-MSA positron emission tomography. According to the imaging study, an increased number of TAMs in responders at the early phase of anti-PD1 treatment was observed in both B16F10-Luc and MC38-Luc tumorbearing mice models. Conclusion As representative immune cells in the TME, non-invasive imaging of TAMs using MSA nanoparticles can refect the immune cell enrichment status in the TME closely associated with the response to anti-PD1. As non-inva‑ sive imaging using MSA nanoparticles, this approach shows a potential to monitor and evaluate anti-tumor response to immune checkpoint inhibitors.This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2020R1A6A3A13069409), the Korean government the Ministry of Science, ICT and Future Planning (2020R1A2C2010202, 2020R1A4A2002903, 2020M3A9B6038086, 2021M2E7A2079570, 2021R1A2C3009427, 2022M3E5F2018261), and the Ministry of Health and Welfare (HI19C0339, HN22C0644). This study also was carried out by the research fund supported by the fund project of Park Yang Sook - Chung Yung Ho in Seoul National University

Direct Synthesis of Molybdenum Phosphide Nanorods on Silicon Using Graphene at the Heterointerface for Efficient Photoelectrochemical Water Reduction

MoP nanorod-array catalysts were directly synthesized on graphene passivated silicon photocathodes without secondary phase. Mo-O-C covalent bondings and energy band bending at heterointerfaces facilitate the electron transfer to the reaction sites. Numerous catalytic sites and drastically enhanced anti-reflectance of MoP nanorods contribute to the high solar energy conversion efficiency. Abstract Transition metal phosphides (TMPs) and transition metal dichalcogenides (TMDs) have been widely investigated as photoelectrochemical (PEC) catalysts for hydrogen evolution reaction (HER). Using high-temperature processes to get crystallized compounds with large-area uniformity, it is still challenging to directly synthesize these catalysts on silicon photocathodes due to chemical incompatibility at the heterointerface. Here, a graphene interlayer is applied between p-Si and MoP nanorods to enable fully engineered interfaces without forming a metallic secondary compound that absorbs a parasitic light and provides an inefficient electron path for hydrogen evolution. Furthermore, the graphene facilitates the photogenerated electrons to rapidly transfer by creating Mo-O-C covalent bondings and energetically favorable band bending. With a bridging role of graphene, numerous active sites and anti-reflectance of MoP nanorods lead to significantly improved PEC-HER performance with a high photocurrent density of 21.8 mA cm−2 at 0 V versus RHE and high stability. Besides, low dependence on pH and temperature is observed with MoP nanorods incorporated photocathodes, which is desirable for practical use as a part of PEC cells. These results indicate that the direct synthesis of TMPs and TMDs enabled by graphene interlayer is a new promising way to fabricate Si-based photocathodes with high-quality interfaces and superior HER performance. Graphic Abstrac