Deciphering Trends in Cancer Mortality: A Comprehensive Analysis of Brazilian Data From 1979 to 2021 With Emphasis on Breast and Prostate Cancers.

Background: This study examined cancer mortality trends in Brazil from 1979 to 2021, emphasizing breast and prostate cancers. Methods: Utilizing data from the Brazilian Mortality Information System and the Brazilian Institute of Geography and Statistics, it analyzed cancer deaths nationally and regionally, highlighting gender-specific and regional disparities. Results: The research finds that cancer death rates have been growing at an average of 12% per year, contrasting with the population growth rate of 2.2%. This trend is more pronounced in the southern and southeastern regions of Brazil. A comparison of cancer mortality rates between Brazil, the USA, and China reveals that while the Brazilian and Chinese rates exhibit slower growth, the US rate shows a continuous decline since the 1990s. Conclusions: The study adopts a novel approach by focusing on growth rates and employing polynomial interpolation, revealing a deceleration in cancer death growth over the last 15 years across all malignant neoplasms. The study also contextualizes these findings within Brazil's cancer control policies, tracing the evolution of preventive measures and treatment advancements. It highlights the significant role of the National Cancer Institute and the Unified Health System in implementing effective strategies. The decreasing trend in cancer mortality rates in Brazil, despite population growth, illustrates the effectiveness of comprehensive cancer control and prevention measures, underlining their importance in public health policy.

Magnesium whitlockite nanoparticles: Hydrothermal synthesis, anti-inflammatory and anti-cancer potential.

This study revealed the potential of magnesium whitlockite [WH: Ca18Mg2(HPO4)2(PO4)12] nanoparticles (WH NPs) for anti-inflammatory and anti-cancer therapies. Although magnesium whitlockite possesses promising biological properties, its effects on inflammation and cancer remain unexplored. In this study, we address this gap by synthesizing WH NPs and demonstrating their multifaceted functionalities. Through detailed characterization, we revealed the synthesis pathway involving brushite as a precursor, with magnesium ions incorporated during hydrothermal treatment. WH NPs exhibited anti-inflammatory properties by significantly reducing the production of key inflammatory markers (NO, TNF-α, and IL-6). Furthermore, they display promising anti-cancer activity by inhibiting the proliferation of MDA-MB-231 breast cancer cells. Our findings not only establish a deeper understanding of WH NP synthesis but also highlight their potential for the development of innovative cancer and inflammatory treatments.

Molecular Imaging for Lung Cancer: Exploring Small Molecules, Peptides, and Beyond in Radiolabeled Diagnostics.

It is evident that radiolabeled drug delivery systems hold great promise in the field of lung cancer management. The combination of therapeutic agents with radiotracers not only allows for precise localization within lung tumors but also enables real-time monitoring of drug distribution. This approach has the potential to enhance targeted therapy and improve patient outcomes. The integration of advanced imaging modalities, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), has played a crucial role in the non-invasive tracking of radiolabeled drugs. These techniques provide valuable insights into drug pharmacokinetics, biodistribution, and tumor-targeting efficiency, offering clinicians the ability to personalize treatment regimens. The comprehensive analysis of preclinical and clinical studies presented in this review underscores the progress made in the field. The evidence suggests that radiolabeled drug delivery systems have the potential to revolutionize oncology by offering precise, targeted, and image-guided therapeutic interventions for lung cancer. This innovative approach not only enhances the effectiveness of treatment but also contributes to the development of personalized medicine strategies, tailoring interventions to the specific characteristics of each patient's cancer. The ongoing research in this area holds promise for further advancements in lung cancer management, potentially leading to improved outcomes and quality of life for patients.

Chia nanoemulsion: anti-inflammatory mechanism, biological behavior and cellular interactions.

Aim: This study explores chia oil, rich in ω-3 fatty acids and nutraceutical components, as a potential remedy for diseases, especially those linked to inflammation and cancer. Methods/materials: A chia oil-based nanoemulsion, developed through single emulsification, underwent comprehensive analysis using various techniques. In vitro and in vivo assays, including macrophage polarization, nitrite and cytokine production, cellular uptake and biodistribution, were conducted to assess the anti-inflammatory efficacy. Results & conclusion: Results reveal that the chia nanoemulsion significantly inhibits inflammation, outperforming pure oil with twice the efficacy. Enhanced uptake by macrophage-like cells and substantial accumulation in key organs indicate its potential as an economical and effective anti-inflammatory nanodrug, addressing global economic and health impacts of inflammation-related diseases.

Micellar solution of [223Ra]RaCl2: Reaching renal excretion, potent efficacy in osteoblastic osteosarcoma in PDX model, biochemistry alterations and pharmacokinetics.

Despite the successful use of the radiopharmaceutical radium-223 dichloride ([223Ra]RaCl2) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [223Ra]RaCl2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 h after intraperitoneal administration as an alternative to overcome the previous limitations. In addition, we evaluated the bone specificity of micellar [223Ra]RaCl2 in patient-derived xenografts in the osteosarcoma model. The biodistribution studies revealed the high bone-targeting properties of the micellar [223Ra]RaCl2. Interestingly, the liver uptake remained significantly low (%ID/g = 0.1-0.02) from 24 to 96 h after administration. In addition, the micellar [223Ra]RaCl2 exhibited a significantly higher uptake in left (%ID/g = 0.85-0.23) and right (%ID/g = 0.76-0.24) kidneys than in small (%ID/g = 0.43-0.06) and large intestines (%ID/g = 0.24-0.09) over time, suggesting its excretion pathway is primarily through the kidneys into the urine, in contrast to the non-micellar [223Ra]RaCl2. The micellar [223Ra]RaCl2 also had low distribution volume (0.055 ± 0.003 L) and longer elimination half-life (28 ± 12 days). This nanosystem was unable to change the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, gamma GT, glucose, and liquiform lipase in the treated mice. Finally, microscopic examination of the animals' osteosarcoma tumors treated with micellar [223Ra]RaCl2 indicated regression of the tumor, with large areas of necrosis. In contrast, in the control group, we observed tumor cellularity and cell anaplasia, mitotic figures and formation of neoplastic extracellular bone matrix, which are typical features of osteosarcoma. Therefore, our findings demonstrated the efficiency and safety of nanosized micellar formulations to minimize the gastrointestinal excretion pathway of the clinical radiopharmaceutical [223Ra]RaCl2, in addition to promoting regression of the osteosarcoma. Further studies must be performed to assess dose-response outcomes and organ/tissue dosimetry for clinical translation.

Radiolabeled Human Serum Albumin Nanoparticles Co-Loaded with Methotrexate and Decorated with Trastuzumab for Breast Cancer Diagnosis.

Breast cancer is a leading cause of cancer-related mortality among women worldwide, with millions of new cases diagnosed yearly. Addressing the burden of breast cancer mortality requires a comprehensive approach involving early detection, accurate diagnosis, effective treatment, and equitable access to healthcare services. In this direction, nano-radiopharmaceuticals have shown potential for enhancing breast cancer diagnosis by combining the benefits of nanoparticles and radiopharmaceutical agents. These nanoscale formulations can provide improved imaging capabilities, increased targeting specificity, and enhanced sensitivity for detecting breast cancer lesions. In this study, we developed and evaluated a novel nano-radio radiopharmaceutical, technetium-99m ([99mTc]Tc)-labeled trastuzumab (TRZ)-decorated methotrexate (MTX)-loaded human serum albumin (HSA) nanoparticles ([99mTc]-TRZ-MTX-HSA), for the diagnosis of breast cancer. In this context, HSA and MTX-HSA nanoparticles were prepared. Conjugation of MTX-HSA nanoparticles with TRZ was performed using adsorption and covalent bonding methods. The prepared formulations were evaluated for particle size, PDI value, zeta (ζ) potential, scanning electron microscopy analysis, encapsulation efficiency, and loading capacity and cytotoxicity on MCF-7, 4T1, and MCF-10A cells. Finally, the nanoparticles were radiolabeled with [99mTc]Tc using the direct radiolabeling method, and cellular uptake was performed with the nano-radiopharmaceutical. The results showed the formation of spherical nanoparticles, with a particle size of 224.1 ± 2.46 nm, a PDI value of 0.09 ± 0.07, and a ζ potential value of -16.4 ± 0.53 mV. The encapsulation efficiency of MTX was found to be 32.46 ± 1.12%, and the amount of TRZ was 80.26 ± 1.96%. The labeling with [99mTc]Tc showed a high labeling efficiency (>99%). The cytotoxicity studies showed no effect, and the cellular uptake studies showed 97.54 ± 2.16% uptake in MCF-7 cells at the 120th min and were found to have a 3-fold higher uptake in cancer cells than in healthy cells. In conclusion, [99mTc]Tc-TRZ-MTX-HSA nanoparticles are promising for diagnosing breast cancer and evaluating the response to treatment in breast cancer patients.

Medicinal (Radio)Chemistry: Building Radiopharmaceuticals for the Future.

Radiopharmaceuticals are increasingly playing a leading role in diagnosing, monitoring, and treating disease. In comparison with conventional pharmaceuticals, the development of radiopharmaceuticals does follow the principles of medicinal chemistry in the context of imaging-altered physiological processes. The design of a novel radiopharmaceutical has several steps similar to conventional drug discovery and some particularity. In the present work, we revisited the insights of medicinal chemistry in the current radiopharmaceutical development giving examples in oncology, neurology, and cardiology. In this regard, we overviewed the literature on radiopharmaceutical development to study overexpressed targets such as prostate-specific membrane antigen and fibroblast activation protein in cancer; ß-amyloid plaques and tau protein in brain disorders; and angiotensin II type 1 receptor in cardiac disease. The work addresses concepts in the field of radiopharmacy with a special focus on the potential use of radiopharmaceuticals for nuclear imaging and theranostics.

Radiolabeled gemcitabine hydrochloride as an imaging agent for lung cancer: Radiolabeling, quality control and cell incorporation studies.

The development of new drugs that can specifically screen tumors is a global need. When it comes to lung cancer, which is the second main cause of cancer-related deaths, early detection of lung tumors using appropriate imaging is very important. In this study, gemcitabine hydrochloride (GCH) was radiolabeled with [99mTc]Tc under different conditions (changing reducing agent, antioxidant agent, incubation time, pH, [99mTc]Tc activity) and radiolabeling activity (quality control) using Radio Thin Layer Chromatography and paper electrophoresis. The results showed that the most stable complex ([99mTc]Tc-GCH) was prepared using 0.015 mg of stannous chloride as a reducing agent, 0.01 mg of ascorbic acid as an antioxidant and 37 MBq activity at pH 7.4 after 15 min of incubation time. The complex remained stable for 6 h. Cell incorporation studies showed a six-fold higher uptake of [99mTc]Tc-GCH in cancer (A-549) cells (38.42 ± 1.53) than healthy (L-929) cells (6.11 ± 0.17) have shown that it can. In addition, the different behaviors of R/H-[99mTc]Tc confirmed the specificity of this newly developed radiopharmaceutical. Although these studies are preliminary, it has been concluded that [99mTc]Tc-GCH may be a candidate drug for use in nuclear medicine, particularly in the diagnosis of lung cancer.

Nanocarriers for Sirna Delivery Aimed at the Treatment of Melanoma: Systematic Review.

BACKGROUND: Melanoma is a malignant skin cancer type with a high lethality rate due to active metastasis. Among the risk factors for its development is exposure to ultraviolet radiation (UV) and phenotypical characteristics such as clear skin and eyes. Given the difficulties of the conventional therapy, the high cost of the treatment and the low bioavailability of drugs, it is important to develop new therapeutic methods to circumvent this situation. Nanosystems such as micelles, liposomes and nanoparticles present advantages when compared to conventional treatments. OBJECTIVE: The objective of this paper is to carry out a literature review based on articles that dealt with the use of siRNA-loaded nanosystems for the treatment of melanoma, with trials carried out in vivo to assess tumor size. METHODS: The search was conducted in the Web of Science and PubMed databases considering the last 5 years, that is, the period between January 2017 to December 2021. The "SiRNA and Drug Delivery Systems and Melanoma" keywords were used in both databases, and the articles were analyzed using the inclusion and exclusion criteria established for this paper. RESULTS: The results obtained indicated that using siRNA transported via nanosystems was capable of silencing the BRAF tumor genes and of reducing tumor size and weight, not presenting in vitro and/or in vivo toxicity. CONCLUSION: Such being the case, the development of these systems becomes a non-invasive and promising option for the treatment of melanoma.

Ionizing Radiation: Chemical Kinetics, Chemical Bounds, and Radiation Chemistry on Polymers.

Ionizing radiation has been used for decades and expanded to several applications in multivariate sectors, becoming an important tool to promote controlled chemical reactions in polymeric structures, according to their chemical properties for developing new materials. In addition, the use of radiation can also be applied in order to reduce or eliminate compounds from solutions that may be harmful or of low interest. In this review, we overviewed the chemistry behind material irradiation and the attractive use of ionizing radiation in scientific and industrial development. In this regard, the review was divided into three main sections titled (1) chemical kinetics intermediated by radiation, (2) chemical bonds intermediated by radiation, and (3) radiation chemistry on polymers. We concluded that graft polymerization, crosslinking and chain scission reactions induced by ionizing radiation are very efficient and green strategies for developing new materials with improved properties. Furthermore, water radiolysis plays a key role in the degradation of several contaminants, including pharmaceuticals and microplastics, in aqueous solutions. However, more studies must be conducted to complement the existing theory about the proposed mechanisms responsible for modifying the chemical, mechanical, thermal, optical, and so forth properties of irradiated materials.

Nano-hydroxyapatite radiolabeled with radium dichloride [223Ra] RaCl2 for bone cancer targeted alpha therapy: In vitro assay and radiation effect on the nanostructure.

The use of targeted alpha therapy (TAT) for bone cancer is increasing each year. Among the alpha radionuclides, radium [223Ra]Ra+2 is the first one approved for bone cancer metastasis therapy. The development of novel radiopharmaceutical based on [223Ra]Ra+2 is essential to continuously increase the arsenal of new TAT drugs. In this study we have developed, characterized, and in vitro evaluated [223Ra] Ra-nano-hydroxyapatite. The results showed that [223Ra] Ra-nano-hydroxyapatite has a dose-response relationship for osteosarcoma cells and a safety profile for human fibroblast cells, corroborating the application as a radiopharmaceutical.

Ultrastructural Analysis of Cancer Cells Treated with the Radiopharmaceutical Radium Dichloride ([223Ra]RaCl2): Understanding the Effect on Cell Structure.

The use of alpha-particle (α-particle) radionuclides, especially [223Ra]RaCl2 (radium dichloride), for targeted alpha therapy is steadily increasing. Despite the positive clinical outcomes of this therapy, very little data are available about the effect on the ultrastructure of cells. The purpose of this study was to evaluate the nanomechanical and ultrastructure effect of [223Ra] RaCl2 on cancer cells. To analyze the effect of [223Ra]RaCl2 on tumor cells, human breast cancer cells (lineage MDA-MB-231) were cultured and treated with the radiopharmaceutical at doses of 2 µCi and 0.9 µCi. The effect was evaluated using atomic force microscopy (AFM) and transmission electron microscopy (TEM) combined with Raman spectroscopy. The results showed massive destruction of the cell membrane but preservation of the nucleus membrane. No evidence of DNA alteration was observed. The data demonstrated the formation of lysosomes and phagosomes. These findings help elucidate the main mechanism involved in cell death during α-particle therapy.

Nano-Nutraceuticals for Health: Principles and Applications.

The use of nanotechnological products is increasing steadily. In this scenario, the application of nanotechnology in food science and as a technological platform is a reality. Among the several applications, the main use of this technology is for the development of foods and nutraceuticals with higher bioavailability, lower toxicity, and better sustainability. In the health field, nano-nutraceuticals are being used as supplementary products to treat an increasing number of diseases. This review summarizes the main concepts and applications of nano-nutraceuticals for health, with special focus on treating cancer and inflammation. Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-022-00338-7.

Development, physicochemical evaluation, and in vivo permeation studies of topical formulations containing 0.1% tacrolimus

Abstract The objective of this paper was to develop and evaluate two semi-solid pharmaceutical forms containing 0.1% tacrolimus: cream (CRT01) and gel (GLT01). For the evaluation of physicochemical stability, at times 0, 30, 60 and 90 days, at 23°C and at 40°C, High Performance Liquid Chromatography coupled with a Diode Array Detector (HPLC-DAD) was employed. This method was developed and validated for tacrolimus quantification. The occlusivity test and skin permeation assay were also performed, using an animal model (Wistar rats), and the CRT01 and GLT01 were compared to the 0.1% tacrolimus ointment (PFU01) obtained from the University Pharmacy, Federal University of Rio de Janeiro, Brazil. CRT01 and GLT01 presented a homogeneous aspect and consistency adequate for topical products, along with sensory characteristics above PFU01. They also presented adequate physicochemical stability for 90 days and a lower occlusive effect than PFU01 (p<0.05). CRT01 showed greater affinity for the skin when compared to PFU01 and GLT01, with low systemic absorption. The CRT01 semi-solid formulation was considered the most adequate one to treat patients with atopic dermatitis or other dermatologic inflammatory diseases, promoting rational use of tacrolimus

Nanomechanical and Vibrational Signature of Chikungunya Viral Particles.

Chikungunya virus (CHIKV) belongs to the genus Alphaviridae, with a single-stranded positive-sense RNA genome of 11.8 kbp encoding a polyprotein that generates both non-structural proteins and structural proteins. The virus is transmitted by the Aedes aegypti and A. albopictus mosquitoes, depending on the location. CHIKV infection leads to dengue-like musculoskeletal symptoms and has been responsible for several outbreaks worldwide since its discovery in 1952. Patients often experience fever, headache, muscle pain, joint swelling, and skin rashes. However, the ultrastructural and mechanical properties of CHIKV have not been fully characterized. Thus, this study aims to apply a physical approach to investigate CHIKV's ultrastructural morphology and mechanical properties, using atomic force microscopy and Raman spectroscopy as the main tools. Using nanomechanical assays of AFM and a gold nanoparticles substrate for Raman signal enhancement, we explored the conformational plasticity, morphology, vibrational signature, and nanomechanical properties of the chikungunya virus, providing new information on its ultrastructure at the nanoscale and offering a novel understanding of the virus' behavior upon mechanical disruptions besides its molecular composition.

Folic acid-functionalized graphene quantum dots: Synthesis, characterization, radiolabeling with radium-223 and antiviral effect against Zika virus infection.

The use of graphene quantum dots as biomedical devices and drug delivery systems has been increasing. The nano-platform of pure carbon has shown unique properties and is approved to be safe for human use. In this study, we successfully produced and characterized folic acid-functionalized graphene quantum dots (GQD-FA) to evaluate their antiviral activity against Zika virus (ZIKV) infection in vitro, and for radiolabeling with the alpha-particle emitting radionuclide radium-223. The in vitro results exhibited the low cytotoxicity of the nanoprobe GQD-FA in Vero E6 cells and the antiviral effect against replication of the ZIKV infection. In addition, our findings demonstrated that functionalization with folic acid doesn't improve the antiviral effect of graphene quantum dots against ZIVK replication in vitro. On the other hand, the radiolabeled nanoprobe 223Ra@GQD-FA was also produced as confirmed by the Energy Dispersive X-Ray Spectroscopy analysis. 223Ra@GQD-FA might expand the application of alpha targeted therapy using radium-223 in folate receptor-overexpressing tumors.

Combined antibiofilm activity of synthetic peptides and antifungal drugs against Candida spp.

Introduction: Candida krusei and Candida albicans are biofilm-forming drug-resistant yeasts that cause bloodstream infections that can lead to death. Materials & methods: nystatin and itraconazole were combined with two synthetic peptides, PepGAT and PepKAA, to evaluate the synergistic effect against Candida biofilms. Additionally, scanning electron and fluorescence microscopies were employed to understand the mechanism behind the synergistic activity. Results: Peptides enhanced the action of drugs to inhibit the biofilm formation of C. krusei and C. albicans and the degradation of mature biofilms of C. krusei. In combination with antifungal drugs, peptides' mechanism of action involved cell wall and membrane damage and overproduction of reactive oxygen species. Additionally, in combination, the peptides reduced the toxicity of drugs to red blood cells. Conclusion: These results reveal that the synthetic peptides enhanced the antibiofilm activity of drugs, in addition to reducing their toxicity. Thus, these peptides have strong potential as adjuvants and to decrease the toxicity of drugs.

Candida krusei and Candida albicans are biofilm-forming, drug-resistant yeasts that cause bloodstream infections that can lead to death. In this study, biofilms of C. krusei and C. albicans were treated with a solution composed of synthetic peptides and antifungal drugs, none of which were effective alone. The synthetic peptides reduced the toxicity of drugs to red blood cells. These results may pave the way to the application of synthetic peptides as a beneficial additional to antifungal drugs to treat fungi that cannot be killed by drugs alone.

Biodistribution of 99mTc-PLA/PVA/Atezolizumab nanoparticles for non-small cell lung cancer diagnosis.

Lung cancer (LC) is a common type of cancer, which is a leading cause of death around the world. There is an urgency for the development of new drugs that could diagnose the LC in the early stages and in a precise manner. In this direction, the development of nanoparticles radiolabeled with the diagnostic radioisotopes represent an important advance in the field of cancer imaging. In this study were developed PLA/PVA/Atezolizumab nanoparticles which were radiolabeled with 99mTc (Technetium-99m). The radiolabeled nanoparticles were evaluated in both: in-vitro (L-929 and A-549) as in-vivo (mice). The results showed no cytotoxicity effect in the healthy cells (L-929) and cytotoxicity effect in the tumor cells (A-549). The biodistribution assay demonstrated that 99mTc-PLA/PVA/Atezolizumab could reach the tumor site 14-folds higher than the nonparticulate atezolizumab. In conclusion, 99mTc-PLA/PVA/Atezolizumab nanoparticles showed to be a new drug which is able to precisely image the lung tumor, and it must be considered for clinical trials.

High doses of graphene quantum dots impacts on microcirculation system: An observational study.

Graphene and its derivatives are in the edge of technology with a wide and diverse range of applications. In the last years, especially graphene quantum dots (GQDs) have had their biomedical application expanded in scope, mainly focused on cancer therapy, drug delivery and imaging. Although many studies have evaluated the application of this nanomaterial in biomedical field, only a few studies aimed to understand their biological impact in human health. In this regard, here we evaluated the impact of high doses of GQDs on the microcirculation of a healthy animal model to better assess risks of its use in humans. Our data show that successive applications of GQDs cause irreversible damage to the microcirculation. After seven days, a complete destruction of the microcirculation has been observed. In addition, GQDs showed substantial activity in human erythrocytes. Our findings suggest that risks associated with the use of GQDs, as well as all graphene derivatives, must be better understood, especially concerning biomedical application. A greater understanding of how GQDs impact body circulation, including the context of environmental and engineered nanosystems, is of paramount importance.

Radiolabeled nanomaterials for biomedical applications: radiopharmacy in the era of nanotechnology.

BACKGROUND: Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. Nanomedicine, a term for the application of nanotechnology in medical and health fields, uses nanoparticles for several applications such as imaging, diagnostic, targeted cancer therapy, drug and gene delivery, tissue engineering, and theranostics. RESULTS: Here, we overview the current state-of-the-art of radiolabeled nanoparticles for molecular imaging and radionuclide therapy. Nanostructured radiopharmaceuticals of technetium-99m, copper-64, lutetium-177, and radium-223 are discussed within the scope of this review article. CONCLUSION: Nanoradiopharmaceuticals may lead to better development of theranostics inspired by ingenious delivery and imaging systems. Cancer nano-theranostics have the potential to lead the way to more specific and individualized cancer treatment.