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In the last three decades, radiopharmaceuticals have proven their effectiveness for cancer diagnosis and therapy. In parallel, the advances in nanotechnology have fueled a plethora of applications in biology and medicine. A convergence of these disciplines has emerged more recently with the advent of nanotechnology-aided radiopharmaceuticals. Capitalizing on the unique physical and functional properties of nanoparticles, radiolabeled nanomaterials or nano-radiopharmaceuticals have the potential to enhance imaging and therapy of human diseases. This article provides an overview of various radionuclides used in diagnostic, therapeutic, and theranostic applications, radionuclide production through different techniques, conventional radionuclide delivery systems, and advancements in the delivery systems for nanomaterials. The review also provides insights into fundamental concepts necessary to improve currently available radionuclide agents and formulate new nano-radiopharmaceuticals.

Dengue virus (DENV) is an arboviral disease affecting more than 400 million people annually. Only a single vaccine formulation is available commercially and many others are still under clinical trials. Despite all the efforts in vaccine designing, the improvement in vaccine formulation against DENV is very much needed. In this study, we used a roboust immunoinformatics approach, targeting all the four serotypes of DENV to design a multi-epitope vaccine. A total of 13501 MHC II binding CD4+ epitope peptides were predicted from polyprotein sequences of four dengue virus serotypes. Among them, ten conserved epitope peptides that were interferon-inducing were selected and found to be conserved among all the four dengue serotypes. The vaccine was formulated using antigenic, non-toxic and conserved multi epitopes discovered in the in-silico study. Further, the molecular docking and molecular dynamics predicted stable interactions between predicted vaccine and immune receptor, TLR-5. Finally, one of the mapped epitope peptides was synthesized for the validation of antigenicity and antibody production ability where the in-vivo tests on rabbit model was conducted. Our in-vivo analysis clearly indicate that the imunogen designed in this study could stimulate the production of antibodies which further suggest that the vaccine designed possesses good immunogenicity.

Substantial interest exists in the effects of immunotherapy; however, radiation therapy also has the potential to stimulate an antitumour immune response. In this Perspectives, the authors describe the rationale for combining immunotherapy with stereotactic ablative radiotherapy based on the available clinical data, and provide recommendations for the future testing of approaches using this combination of treatments. Conventional radiotherapy, in addition to its well-established tumoricidal effects, can also activate the host immune system. Radiation therapy modulates tumour phenotypes, enhances antigen presentation and tumour immunogenicity, increases production of cytokines and alters the tumour microenvironment, enabling destruction of the tumour by the immune system. Investigating the combination of radiotherapy with immunotherapeutic agents, which also promote the host antitumour immune response is, therefore, a logical progression. As the spectrum of clinical use of stereotactic radiotherapy continues to broaden, the question arose as to whether the ablative radiation doses used can also stimulate immune responses and, if so, whether we can amplify these effects by combining immunotherapy and stereotactic ablative radiotherapy (SABR). In this Perspectives article, we explore the preclinical and clinical evidence supporting activation of the immune system following SABR. We then examine studies that provide data on the effectiveness of combining these two techniques — immunotherapy and SABR — in an approach that we have termed 'ISABR'. Lastly, we provide general guiding principles for the development of future clinical trials to investigate the efficacy of ISABR in the hope of generating further interest in these exciting developments.

Owing to unique facets, such as large surface area, tunable synthesis parameters, and ease of functionalization, mesoporous silica nanoparticles (MSNs) have transpired as a worthwhile platform for cancer theranostics over the last decade. The full potential of MSNs in cancer theranostics, however, is yet to be realized. While MSNs can be employed for targeted drug delivery and imaging, their effectiveness can frequently be hindered by factors, such as biological barriers, complex tumor microenvironment, target non-specificity and ineffectiveness of individual functionalized moieties. The primary purpose of this review is to highlight technological advances such as tumor-specific, stimuli-responsive “smart” MSNs and multimodal MSN-based hybrid nanoplatforms that have the potential to overcome these limitations and improve MSN effectiveness in cancer theranostics. This article offers an extensive overview of MSN technology in cancer theranostics, outlining key directions for future research as well as the challenges that are involved in this aspect. We aim to underline the vitality of MSN technology and the relevance of current research and advancements in this field to potentially enhance clinical outcomes through the provision of more precise and focused theranostic approaches.

Radiation therapy (RT), an integral component of curative treatment for many malignancies, can be administered via an increasing array of techniques. In this review, we summarize the properties and application of different types of RT, specifically, conventional therapy with x-rays, stereotactic body RT, and proton and carbon particle therapies. We highlight how low-linear energy transfer (LET) radiation induces simple DNA lesions that are efficiently repaired by cells, whereas high-LET radiation causes complex DNA lesions that are difficult to repair and that ultimately enhance cancer cell killing. Additionally, we discuss the immunogenicity of radiation-induced tumor death, elucidate the molecular mechanisms by which radiation mounts innate and adaptive immune responses and explore strategies by which we can increase the efficacy of these mechanisms. Understanding the mechanisms by which RT modulates immune signaling and the key players involved in modulating the RT-mediated immune response will help to improve therapeutic efficacy and to identify novel immunomodulatory drugs that will benefit cancer patients undergoing targeted RT.

At present, viral diseases become major concern for the world. SARS-CoV2 and SFTS viruses are deadly in nature, and there is a need for developing best treatments for them. Modern in silico approaches were found to be very handy in determining putative drug molecules. In this study, we analyze interaction of beta-sesquiphellandrene (compound belongs to ginger) with spike protein (Sp) and membrane glycoprotein polyprotein (MPp). Our molecular docking and simulation study reveals the perfect binding pocket of Sp and MPp holding beta-sesquiphellandrene (bS). Binding energies for MPp-bS and Sp-bS were found to be - 9.5 kcal/mol and - 10.3 kcal/mol respectively. RMSD and RMSF values for docked complexes were found to be in selectable range, i.e., 1 to 3 Å and 1 to 8 Å respectively. Modern computational tools were used here to make this investigation fast and effective. Further, ADME analysis reveals the therapeutic validations for beta-sesquiphellandrene to act as a useful pharmacoactive compound. Beta-sesquiphellandrene provides not only inhibitory effect on spike protein of SARS-CoV2 but also similar inhibitory effects on membrane glycoprotein polyprotein complex of SFTS virus, which hampers the pathological initiation of the diseases caused by both the viruses, i.e., COVID-19 and severe fever with thrombocytopenia syndrome. This method of computational analysis was found to be rapid and effective, and opens new doors in the domain of in silico drug discovery. Beta-sesquiphellandrene can be used as effective medicine to control these harmful pathogens after wet lab validations.

X-ray fluorescence computed tomography (XFCT) is a technique that can identify, quantify and locate elements within objects by detecting x-ray fluorescence (characteristic x-rays) stimulated by an excitation source, typically derived from a synchrotron. However, the use of a synchrotron limits practicality and accessibility of XFCT for routine biomedical imaging applications. Therefore, we have developed the ability to perform XFCT on a benchtop setting with ordinary polychromatic x-ray sources. Here, we report our postmortem study that demonstrates the use of benchtop XFCT to accurately image the distribution of gold nanoparticles (GNPs) injected into a tumor-bearing mouse. The distribution of GNPs as determined by benchtop XFCT was validated using inductively coupled plasma mass spectrometry. This investigation shows drastically enhanced sensitivity and specificity of GNP detection and quantification with benchtop XFCT, up to two orders of magnitude better than conventional x-ray CT. The results also reaffirm the unique capabilities of benchtop XFCT for simultaneous determination of the spatial distribution and concentration of nonradioactive metallic probes, such as GNPs, within the context of small animal imaging. Overall, this investigation identifies a clear path toward in vivo molecular imaging using benchtop XFCT techniques in conjunction with GNPs and other metallic probes.

Recent reports have shown that very high dose rate radiation (35–100 Gy/second) referred to as FLASH tends to spare the normal tissues while retaining the therapeutic effect on tumor. We undertook a series of experiments to assess if ultra-high dose rate of 35 Gy/second can spare the immune system in models of radiation induced lymphopenia. We compared the tumoricidal potency of ultra-high dose rate and conventional dose rate radiation using a classical clonogenic assay in murine pancreatic cancer cell lines. We also assessed the lymphocyte sparing potential in cardiac and splenic irradiation models of lymphopenia and assessed the severity of radiation-induced gastrointestinal toxicity triggered by the two dose rate regimes in vivo . Ultra-high dose rate irradiation more potently induces clonogenic cell death than conventional dose rate irradiation with a dose enhancement factor at 10% survival (DEF 10 ) of 1.310 and 1.365 for KPC and Panc02 cell lines, respectively. Ultra-high dose rate was equally potent in depleting CD3, CD4, CD8, and CD19 lymphocyte populations in both cardiac and splenic irradiation models of lymphopenia. Radiation-induced gastrointestinal toxicity was more pronounced and mouse survival (7 days vs . 15 days, p  = 0.0001) was inferior in the ultra-high dose rate arm compared to conventional dose rate arm. These results suggest that, contrary to published data in other models of radiation-induced acute and chronic toxicity, dose rates of 35 Gy/s do not protect mice from the detrimental side effects of irradiation in our models of cardiac and splenic radiation-induced lymphopenia or gastrointestinal mucosal injury.

Inflammation plays a major role in cancer development and progression and has the potential to be used as a prognostic marker in cancer. Previous studies have attempted to evaluate Platelet-to-lymphocyte ratio (PLR), neutrophil–lymphocyte ratio (NLR) or monocyte–lymphocyte ratio (MLR) as indicators of inflammation/prognostic markers in cancer, but there is no common consensus on their application in clinical practice. The aim of this systematic review and meta-analysis is to (a) assess the prognostic efficacy of all three prognostic markers in comparison to each other and (b) investigate the prognostic potential of these three markers in HNC. The study followed PRISMA guidelines, with the literature being collated from multiple bibliographic databases. Preliminary and secondary screening were carried out using stringent inclusion/exclusion criteria. Meta-analysis was carried out on selected studies using CMA software and HR as the pooled effect size metric. A total of 49 studies were included in the study. The pooled HR values of PLR, NLR and MLR indicated that they were significantly correlated with poorer OS. The pooled effect estimates for PLR, NLR and MLR were 1.461 (95% CI 1.329–1.674), 1.639 (95% CI 1.429–1.880) and 1.002 (95% CI 0.720–1.396), respectively. Significant between-study heterogeneity was observed in the meta-analysis of all three. The results of this study suggest that PLR, NLR and MLR ratios can be powerful prognostic markers in head and neck cancers that can guide treatment. Further evidence from large-scale clinical studies on patient cohorts are required before they can be incorporated as a part of the clinical method. PROSPERO Registration ID: CRD42019121008

Carbon ion radiation therapy (CIRT) is a high-LET radiotherapy, which distinguishes itself from traditional low-LET radiation, such as photons and protons, through its unique physical aspects, biological attributes, and the dramatically increased damage it causes within cellular DNA. Given its distinctive characteristics, it is expected to improve the therapeutic ratio of radiation treatments and enhance treatment outcomes in traditionally radiation-resistant tumor histologies. Despite these unique properties, much remains to be understood regarding the clinical use of CIRT before its full potential can be realized. In this review, we summarize the distinct advantages of CIRT with regard to its physical and biological qualities and discuss the possibilities for novel applications of this technology through the exploitation of its immunomodulatory potential, abscopal impacts, and its ability to generate direct, oxygen-independent radiation damage within treated tumors.