Delivery efficiencies of theranostic nanoparticles (NPs) based on passive tumor targeting strongly depend either on their blood circulation time or on appropriate modulations of the tumor microenvironment. Therefore, predicting the NP delivery efficiency before and after a tumor microenvironment modulation is highly desirable. Here, we present a new erythrocyte membranecamouflaged magnetofluorescent nanocarrier (MMFn) with long blood circulation time (92 h) and high delivery efficiency (10% ID for Ehrlich murine tumor model). MMFns owe their magnetic and fluorescent properties to the incorporation of manganese ferrite nanoparticles (MnFe 2 O 4 NPs) and IR-780 (a lipophilic indocyanine fluorescent dye), respectively, to their erythrocyte membrane-derived camouflage. MMFn composition, morphology, and size, as well as optical absorption, zeta potential, and fluorescent, magnetic, and magnetothermal properties, are thoroughly examined in vitro. We then present an analytical pharmacokinetic (PK) model capable of predicting the delivery efficiency (DE) and the time of peak tumor uptake (t max ), as well as changes in DE and t max due to modulations of the tumor microenvironment, for potentially any nanocarrier. Experimental PK data sets (blood and tumor amounts of MMFns) are simultaneously fit to the model equations using the PK modeling software Monolix. We then validate our model analytical solutions with the numerical solutions provided by Monolix. We also demonstrate how our a priori nonmechanistic model for passive targeting relates to a previously reported mechanistic model for active targeting. All in vivo PK studies, as well as in vivo and ex vivo biodistribution studies, were conducted using two noninvasive techniques, namely, fluorescence molecular tomography (FMT) and alternating current biosusceptometry (ACB). Finally, histopathology corroborates our PK and biodistribution results.
IR-780 iodide is a fluorescent dye with optical properties in the near-infrared region that has applications in tumor detection and photothermal/photodynamic therapy. This multifunctional effect led to the development of theranostic nanoparticles with both IR-780 and chemotherapeutic drugs such as docetaxel, doxorubicin, and lonidamine. In this work, we developed two albumin-based nanoparticles containing nearinfrared IR-780 iodide multifunctional dyes, one of them possessing a magnetic core. Molecular docking with AutoDock Vina studies showed that IR-780 binds to bovine serum albumin (BSA) with greater stability at a higher temperature, allowing the protein binding pocket to better fit this dye. The theoretical analysis corroborates the experimental protocols, where an enhancement of IR-780 was found coupled to BSA at 60 °C, even 30 days after preparation, in comparison to 30 °C. In vitro assays monitoring the viability of Ehrlich ascites carcinoma cells revealed the importance of the inorganic magnetic core on the nanocarrier photothermal−cytotoxic effect. Fluorescence molecular tomography measurements of Ehrlich tumor-bearing Swiss mice revealed the biodistribution of the nanocarriers, with marked accumulation in the tumor tissue (≈3% ID). The histopathological analysis demonstrated strong increase in tumoral necrosis areas after 24 and 72 h after treatment, indicating tumor regression. Tumor regression analysis of nonirradiated animals indicate a IR-780 dose-dependent antitumoral effect with survival rates higher than 70% (animals monitored up to 600 days). Furthermore, an in vivo photothermal therapy procedure was performed and tumor regression was also verified. These results show a novel insight for the biomedical application of IR-780-albumin-based nanocarriers, namely cancer therapy, not only by photoinduced therapy but also by a nonirradiation mechanism. Safety studies (acute oral toxicity, cardiovascular evaluation, and histopathological analysis) suggest potential for clinical translation.
Chagas disease is the main cause of heart failure and sudden death in the Western Hemisphere. The literature of the last decades reported on the changing epidemiological profiles of Chagas disease, which now threats the human population in the cities. The exodus of the Latin America people to the Northern Hemisphere explains the growing concern in countries where the transmission of Trypanosoma cruzi was accidental or transferred from a mother to her offspring. Herein, we present the evidence of the possible acquisition of the T. cruzi infection by sex. The staggering demonstration of the transmission of the T. cruzi infections from males and females to naïve mates by intercourse introduces substantial changes in the surveillance of the Chagas disease. Notably, the sexual transmission of the T. cruzi introduces changes in the concepts of medical care, prevention and control; specifically, the risk for the vertical transfer of the parasiteinduced kDNA mutations, underpinning the genetically driven autoimmunity, inheritance, and pathogenesis associated with multifaceted clinical manifestations of Chagas disease with high
Antimetastatic activity, high selectivity and cytotoxicity for human tumor cell lines make ruthenium(ii) complexes attractive for the development of new chemotherapeutic agents for cancer treatment.
Serological survey was performed to detect IgG antibodies anti-Taenia solium metacestodes in blood donors of Hemocentro Regional de Uberlândia, Minas Gerais, Brazil. A total of 1133 sera from blood donors coming from four cities of Triângulo Mineiro area were analyzed by the indirect fluorescence antibody test (IFAT) and the enzyme linked immunosorbent assay (ELISA). Specific IgG antibodies were found in 5.6% of the studied population, showing differences in the positive rates according to their origin: Araguari (13.5%), Tupaciguara (5.0%), Monte Alegre de Minas (4.8%) and Uberlândia (4.7%). The results indicate the probable endemicity of cysticercosis in this population.
Objective
To evaluate the secondary attack rate (SAR) in children and adolescents, contacts of essential activities workers who were infected by SARS‐CoV‐2; and to describe associated clinical and epidemiological data.
Methods
A cross‐sectional study conducted in children and adolescents aged 5 to 19 years of age, that were household contacts of parents and other relatives who were infected by SARS‐CoV‐2 in the city of Goiânia, Central Brazil, from March to October 2020. Sociodemographic and clinical data were collected from all participants. Nasopharyngeal and oropharyngeal swabs were collected and tested for SARS‐CoV‐2 RNA using real‐time reverse transcription polymerase chain reaction (RT‐PCR). Factors associated with SARS‐CoV‐2 infection and SAR were analyzed using Poisson regression.
Results
A total of 267 children and adolescents were investigated. The prevalence of SARS‐CoV‐2 RNA by the real‐time RT‐PCR test and/or the presence of COVID‐19 associated symptoms (anosmia/ageusia and flu syndrome) was 25.1% (95.0% Confidence Interval [95.0% CI] = 20.3‐30.6). More than half (55.1%) of the participants had sygns and symptoms. The most prevalent signs and symptoms in positive individuals were nasal congestion (62.7%), headache (55.2%), cough (50.8%), myalgia (47.8%), runny nose (47.8%), and anosmia (47.8%). The Poisson model showed that the following signs or symptoms were associated with SARS‐CoV‐2 infection: fever, nasal congestion, decreased appetite, nausea, anosmia, and ageusia. Families that had more than one infected adult, in addition to the index case, presented greater transmissibility to children and adolescents.
Conclusions
Our results contribute to the hypothesis that children and adolescents are not important sources of transmission of SARS‐CoV‐2 in the home environment during a period of social distancing and school closure; even though they are susceptible to infection in the household (around ¼ of our study population).
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