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Born in fire. Raised by monsters. Destined to smash! On an alien planet shattered by war, no one is stronger than Skaar -- the savage Son of Hulk! But as a warlord and a princess spread chaos through the wastelands, will Skaar save the puny survivors -- or eat them? Skaar seeks the mysterious Old Power, but can even he stop the coming of the Silver Surfer-and Galactus the Devourer? The soothsayers sing: One day, monsters will clash -- the boy will confront the man who abandoned him. When the Son of Hulk seeks vengeance on his father, will Earth be turned into Planet Skaar?

Radiotherapy is an essential component of the treatment regimens for many cancer patients. Despite recent technological advancements to improve dose delivery techniques, the dose escalation required to enhance tumor control is limited due to the inevitable toxicity to the surrounding healthy tissue. Therefore, the local enhancement of dosing in tumor sites can provide the necessary means to improve the treatment modality. In recent years, the emergence of nanotechnology has facilitated a unique opportunity to increase the efficacy of radiotherapy treatment. The application of high-atomic-number (Z) nanoparticles (NPs) can augment the effects of radiotherapy by increasing the sensitivity of cells to radiation. High-Z NPs can inherently act as radiosensitizers as well as serve as targeted delivery vehicles for radiosensitizing agents. In this work, the therapeutic benefits of high-Z NPs as radiosensitizers, such as their tumor-targeting capabilities and their mechanisms of sensitization, are discussed. Preclinical data supporting their application in radiotherapy treatment as well as the status of their clinical translation will be presented.

The success of nanoparticle-based cancer therapeutics relies on their efficient tumor uptake and retention. Given this, improving nanoparticle localization in tumors is paramount to maximize their therapeutic potential. A common approach to achieve this is to functionalize nanoparticles with active targeting moieties that bind to specific tumor-associated receptors. Among these, arginine-glycine-aspartic acid (RGD) peptides have shown a potential to promote tumor accumulation by targeting the α ν β 3 integrin receptor, a receptor commonly overexpressed by tumors owing to its role in promoting angiogenesis, metastasis and proliferation. Yet, its efficacy is commonly assessed using immunocompromised mice models. While useful, these models do not accurately account for immune-related interactions, which could lead to an overestimation of targeting efficacy. In our study, we investigated the efficacy of RGD peptides to improve the tumor accumulation of PEGylated gold nanoparticles (GNPs) using an immunocompetent mouse model. While RGD functionalization increased GNP uptake in cancer cells in vitro, it significantly reduced tumor accumulation in vivo due to enhanced off-target clearance by the mononuclear phagocyte system, with elevated accumulation in the spleen and liver. These findings highlight that RGD functionalization can promote immune-driven clearance in vivo, despite improving GNP uptake in cancer cells in vitro, emphasizing the importance of assessing targeting strategies in immunocompetent models for more physiologically relevant assessments.

Cancer is defined as the uncontrolled proliferation of heterogeneous cell cultures in the body that develop abnormalities and mutations, leading to their resistance to many forms of treatment. Left untreated, these abnormal cell growths can lead to detrimental and even fatal complications for patients. Radiation therapy is involved in around 50% of cancer treatment workflows; however, it presents significant recurrence rates and normal tissue toxicity, given the inevitable deposition of the dose to the surrounding healthy tissue. Chemotherapy is another treatment modality with excessive normal tissue toxicity that significantly affects patients’ quality of life. To improve the therapeutic efficacy of radiotherapy and chemotherapy, multiple conjunctive modalities have been proposed, which include the targeting of components of the tumour microenvironment inhibiting tumour spread and anti-therapeutic pathways, increasing the oxygen content within the tumour to revert the hypoxic nature of the malignancy, improving the local dose deposition with metal nanoparticles, and the restriction of the cell cycle within radiosensitive phases. The tumour microenvironment is largely responsible for inhibiting nanoparticle capture within the tumour itself and improving resistance to various forms of cancer therapy. In this review, we discuss the current literature surrounding the administration of molecular and nanoparticle therapeutics, their pharmacokinetics, and contrasting mechanisms of action. The review aims to demonstrate the advancements in the field of conjugated nanomaterials and radiotherapeutics targeting, inhibiting, or bypassing the tumour microenvironment to promote further research that can improve treatment outcomes and toxicity rates.

Wastewater surveillance has played a pivotal role in monitoring SARS-CoV-2 transmission worldwide. However, developing and implementing the methods underpinning these programmes in regions with prolonged periods of low community transmission has proven challenging. In Victoria, Australia, wastewater surveillance provided early warning of unknown community infections and informed timely public health decisions to limit their spread when case numbers were low. To achieve this, we developed a methodological approach sensitive to extremely low viral loads and could readily identify false positives within short turnaround times. Here, we describe the successful development, implementation, and evaluation of analytic methods using Reverse Transcriptase Quantitative Polymerase Chain Reaction (RT-qPCR) and amplicon sequencing in tandem with CRISPR DETECTR in an ongoing, large-scale surveillance programme to detect SARS-CoV-2 in wastewater in Victoria, Australia. Our study covers ten months, from July 2020 to April 2021, and includes all state-wide health districts and prolonged periods with no known, active community cases among the ∼6.7 million population.

Background Radiotherapy (RT) is an essential component in the treatment regimens for many cancer patients. However, the dose escalation required to improve curative results is hindered due to the normal tissue toxicity that is induced. The introduction of radiosensitizers to RT treatment is an avenue that is currently being explored to overcome this issue. By introducing radiosensitizers into tumor sites, it is possible to preferentially enhance the local dose deposited. Gold nanoparticles (GNPs) are a potential candidate that have shown great promise in increasing the radiosensitivity of cancer cells through an enhancement in DNA damage. Furthermore, docetaxel (DTX) is a chemotherapeutic agent that arrests cells in the G2/M phase of the cell cycle, the phase most sensitive to radiation damage. We hypothesized that by incorporating DTX to GNP-enhanced radiotherapy treatment, we could further improve the radiosensitization experienced by cancer cells. To assess this strategy, we analyzed the radiotherapeutic effects on monolayer cell cultures in vitro, as well as on a mice prostate xenograft model in vivo while using clinically feasible concentrations for both GNPs and DTX. Results The introduction of DTX to GNP-enhanced radiotherapy further increased the radiotherapeutic effects experienced by cancer cells. A 38% increase in DNA double-strand breaks was observed with the combination of GNP/DTX vs GNP alone after a dose of 2 Gy was administered. In vivo results displayed significant reduction in tumor growth over a 30-day observation period with the treatment of GNP/DTX/RT when compared to GNP/RT after a single 5 Gy dose was given to mice. The treatment strategy also resulted in 100% mice survival, which was not observed for other treatment conditions. Conclusions Incorporating DTX to work in unison with GNPs and RT can increase the efficacy of RT treatment. Our study suggests that the treatment strategy could improve tumor control through local dose enhancement. As the concentrations used in this study are clinically feasible, there is potential for this strategy to be translated into clinical settings.

This research underscores the potential of combining nanotechnology with conventional therapies in cancer treatment, particularly for challenging cases like pancreatic cancer. We aimed to enhance pancreatic cancer treatment by investigating the synergistic effects of gold nanoparticles (GNPs) and docetaxel (DTX) as potential radiosensitizers in radiotherapy (RT) both in vitro and in vivo, utilizing a MIA PaCa-2 monoculture spheroid model and NRG mice subcutaneously implanted with MIA PaCa-2 cells, respectively. Spheroids were treated with GNPs (7.5 μg/mL), DTX (100 nM), and 2 Gy of RT using a 6 MV linear accelerator. In parallel, mice received treatments of GNPs (2 mg/kg), DTX (6 mg/kg), and 5 Gy of RT (6 MV linear accelerator). In vitro results showed that though RT and DTX reduced spheroid size and increased DNA DSBs, the triple combination of DTX/RT/GNPs led to a significant 48% (p = 0.05) decrease in spheroid size and a 45% (p = 0.05) increase in DNA DSBs. In vivo results showed a 20% (p = 0.05) reduction in tumor growth 20 days post-treatment with (GNPs/RT/DTX) and an increase in mice median survival. The triple combination exhibited a synergistic effect, enhancing anticancer efficacy beyond individual treatments, and thus could be employed to improve radiotherapy and potentially reduce adverse effects.

The accurate measurement of three-dimensional (3D) fiber orientation in the brain is crucial for reconstructing fiber pathways and studying their involvement in neurological diseases. Comprehensive reconstruction of axonal tracts and small fascicles requires high-resolution technology beyond the ability of current in vivo imaging (e.g., diffusion magnetic resonance imaging). Optical imaging methods such as polarization-sensitive optical coherence tomography (PS-OCT) can quantify fiber orientation at micrometer resolution but have been limited to two-dimensional in-plane orientation, preventing the comprehensive study of connectivity in 3D. In this work we present a novel method to quantify volumetric 3D orientation in full angular space with PS-OCT in postmortem human brain tissues. We measure the polarization contrasts of the brain sample from two illumination angles of 0 and 15° and apply a computational method that yields the 3D optic axis orientation and true birefringence. We further present 3D fiber orientation maps of entire coronal cerebrum sections and brainstem with 10 μm in-plane resolution, revealing unprecedented details of fiber configurations. We envision that our method will open a promising avenue towards large-scale 3D fiber axis mapping in the human brain as well as other complex fibrous tissues at microscopic level.

Cancer treatments are limited by poor tumor specificity and toxicity. We tested a radiosensitizing approach using PEG/RGD-functionalized gold nanoparticles (GNPs), a lipid-nanoparticle–encapsulated docetaxel prodrug (LNPDTX–P), and external-beam radiotherapy (RT). In MIA PaCa-2 xenografts, intravenous GNPs (2 mg/kg) and LNPDTX–P (6 mg/kg) were given before 5 Gy RT. Both LNPDTX–P + RT and GNPs + LNPDTX–P + RT reduced tumor volume by ~40% and significantly prolonged survival versus RT alone (p < 0.001). Adding GNPs did not enhance efficacy, indicating LNPDTX–P was the main driver under this regimen. These results demonstrate nanocarrier-enabled radiosensitization in vivo and support further studies toward clinical translation.

Radiation therapy (RT) is frequently used to locally treat tumors. One of the major issues in RT is normal tissue toxicity; thus, it is necessary to limit dose escalation for enhanced local control in patients that have locally advanced tumors. Integrating radiosensitizing agents such as gold nanoparticles (GNPs) into RT has been shown to greatly increase the cure rate of solid tumors. The objective of this study was to explore the repurposing of an antimalarial drug, pyronaridine (PYD), as a DNA repair inhibitor to further enhance RT/GNP-induced DNA damage in cancerous cell lines. We were able to achieve inhibitory effects of DNA repair due to PYD at 500 nM concentration. Our results show a significant enhancement in DNA double-strand breaks of 42% in HeLa cells treated with PYD/GNP/RT in comparison to GNP/RT alone when irradiated with a dose of 2 Gy. Furthermore, there was a significant reduction in cellular proliferation for both HeLa and HCT-116 irradiated cells with the combined treatment of PYD/GNP/RT. Therefore, the emergence of promising novel concepts introduced in this study could lay the foundation for the transition of this treatment modality into clinical environments.