Although there are several studies reporting the promising biological efficiency of mesoporous silica nanoparticles (loaded with antitumoral drugs) against cancer cells and tumors, there are no reports on the influence of the bio-nano interface interactions on the molecular diffusion process occurring along their pores. In this context, we show here that the protein coating formed on multifunctionalized colloidal mesoporous silica nanoparticles (MSNs) dispersed in a cell culture medium decreases the release of camptothecin (CPT, a hydrophobic antitumoral drug) from the pores of MSNs. This effect is related to the adsorption of biomolecules on the nanoparticle surface, which partially blocks the pores. Parallely, the hydrophobic functionalization inside the pores can offer suitable sites for the adsorption of other molecules present in the cell culture medium depending on the hydrophobicity, size, and conformation aspects of these molecules and adsorption sites of MSNs. Thus, the molecular cargo loaded in the pores (i.e. CPT) can be replaced by specific molecules present in the dispersion medium. As a consequence, we show that a non-permeable cellular staining molecule such as SYTOX green can be incorporated in MSNs through this mechanism and internalized by cells in an artificial fashion. By extrapolating this phenomenon for applications in vivo, one has to consider now the possible manifestation of unpredicted biological effects from the use of porous silica nanoparticles and others with similar structure due to these internalization aspects.
Nanopartículas mesoporosas de sílica são conhecidas por induzirem hemólise de células vermelhas do sangue (RBCs) humano quando ensaios de citotoxicidade são feitos em solução-tampão de fosfato (PBS). Entretanto, em uma abordagem mais realista, a presença de biomoléculas do plasma sanguíneo precisa ser considerada em qualquer avaliação nanotoxicológica de nanopartículas porosas de SiO 2 quando se objetiva a sua utilização em aplicações biomédicas através de administração intravenosa. Nesse contexto, demonstrou-se neste trabalho que nanopartículas porosas de sílica não induzem nenhum efeito citotóxico em células vermelhas do sangue quando ensaios de hemólise são feitos na presença de plasma sanguíneo, independentemente da carga superficial (positiva ou negativa) da nanopartícula. A ausência de hemólise está principalmente associada à adsorção de proteínas do plasma sobre a superfície das nanopartículas, levando à formação de um recobrimento proteico estável (denominado protein corona ou PC) que blinda o ambiente microquímico original das nanopartículas.Mesoporous silica nanoparticles are known to induce the hemolysis of human red blood cells (RBCs) when citotoxicity assays are performed in a phosphate buffer solution (PBS). However, in a more realistic approach, the presence of blood plasma biomolecules must be considered in any nanotoxicological evaluation of porous SiO 2 nanoparticles when biomedical applications through intravenous administration are aimed. In this context, it is demonstrated in this work that porous silica nanoparticles do not induce any cytotoxic effect on RBCs when hemolysis assay is done in the presence of blood plasma, regardless the surface charge (positive or negative) of the nanoparticle. The absence of hemolysis is mainly associated with the adsorption of plasma proteins on the nanoparticle surface, which leads to the formation of a stable protein coating (called protein corona or PC) that shields the original microchemical environment of bare nanoparticles.Keywords: nanoparticles, SiO 2 , mesopores, hemolytic effect, protein corona IntroductionSince porous silica nanoparticles were elected as possible protagonists in a future revolution of several medical processes of theranosis, they have been widely studied during the last decade through the host-guest approach, thus resulting in promising perspectives mainly in the areas of detection 1-3 and treatment of tumors. [4][5][6][7] While part of the scientific community creatively advances towards the engineering of porous silica nanostructures, others are acting in a proactive approach by considering environmental and toxicological effects of nano-based silica materials. In the latter context, several in vitro citotoxicity assays indicated a very high biocompatibility of porous silica nanoparticles. [8][9][10] However, a desirable in vivo biocompatibility is not straightforward. For instance, it is well known that amorphous silica particles induce toxicity on human red blood cells (RBCs) and, consequently, this test is being used as a ke...
Canthin-6-one presents an interesting cytotoxic activity against leukemic cells and represents a promising scaffold for the development of molecules for anti-leukemic applications, especially by its anti-leukemic stem cell activity.
Several reports have shown the presence of P2 receptors in hematopoietic stem cells (HSCs). These receptors are activated by extracellular nucleotides released from different sources. In the hematopoietic niche, the release of purines and pyrimidines in the milieu by lytic and nonlytic mechanisms has been described. The expression of P2 receptors from HSCs until maturity is still intriguing scientists. Several reports have shown the participation of P2 receptors in events associated with modulation of the immune system, but their participation in other physiological processes is under investigation. The presence of P2 receptors in HSCs and their ability to modulate this population have awakened interest in exploring the involvement of P2 receptors in hematopoiesis and their participation in hematopoietic disorders. Among the P2 receptors, the receptor P2X7 is of particular interest, because of its different roles in hematopoietic cells (e.g., infection, inflammation, cell death and survival, leukemias and lymphomas), making the P2X7 receptor a promising pharmacological target. Additionally, the role of P2Y12 receptor in platelet activation has been well-documented and is the main example of the importance of the pharmacological modulation of P2 receptor activity. In this review, we focus on the role of P2 receptors in the hematopoietic system, addressing these receptors as potential pharmacological targets.
The objective of this work was to study the insecticidal effect of labramin, a protein that shows lectin—like properties. Labramin was isolated from seeds of the Beach Apricot tree, Labramia bojeri A. DC ex Dubard (Ericales: Sapotaceae), and assessed against the development of the Mediterranean flour moth Ephestia kuehniella Zeller (Lepidoptera: Pyralidae), an important pest of stored products such as corn, wheat, rice, and flour. Results showed that labramin caused 90% larval mortality when incorporated in an artificial diet at a level of 1% (w/w). The presence of 0.25% labramin in the diet affected the larval and pupal developmental periods and the percentage of emerging adults. Treatments resulted in elevated levels of trypsin activity in midgut and fecal materials, indicating that labramin may have affected enzyme—regulatory mechanisms by perturbing peritrophic membranes in the midgut of is. kuehniella larvae. The results of dietary experiments with E. kuehniella larvae showed a reduced efficiency for the conversion of ingested and digested food, and an increase in approximate digestibility and metabolic cost. These findings suggest that labramin may hold promise as a control agent to engineer crop plants for insect resistance.
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