Background: As a therapeutic target for cancer treatment, HSP90 has been explored extensively. However, the significant side effects of the HSP90 inhibitor 17AAG have limited its clinical use. Methods: In this study, we used hyaluronic acid (HA)-decorated DOTAP-PLGA hybrid nanoparticles (HA-DOTAP-PLGA NPs) as 17AAG-delivery carriers for targeted colon cancer therapy. Results: Different methods were used to characterize the successful fabrication of these hybrid PLGA NPs. Our results demonstrated that internalization of HA-NPs in colon cancer cells was governed by CD44receptor-mediated endocytosis. Annexin V-propidium iodide staining experiments revealed that cell apoptosis induced by HA-NPs-17AAG in colon cancer cells was more efficient than free 17AAG. In two animal models used to screen anticancer efficacy (Luc-HT29 subcutaneous xenograft and AOM/DSS-induced orthotopic tumor model), HA-NPs -17AAG significantly inhibited xenograft and orthotopic tumor growth, demonstrating HA-NPs -17AAG had much better therapeutic efficiency than free 17AAG. It is worth noting that great biocompatibility of HA-DOTAP-PLGA NPs was observed both in vitro and in vivo.
Conclusion:Our research offers a preclinical proof of concept for colon cancer therapy with DOTAP-PLGA NPs as a creative drug-delivery system.
AbstractThis study aimed to investigate the mechanism of mangiferin on regulating endoplasmic reticulum (ER) stress in acute liver injury. The mouse model of acute liver injury was established by injection of LPS/D-GalN. The primary mouse hepatocytes were stimulated with LPS to induce the in vitro model. The effect of miR-20a/101a on the luciferase activity of Nrf2 3′-UTR was assessed by luciferase reporter assay. Mangiferin improved the liver function, inhibited the oxidative stress and ER stress and down-regulated the expressions of miR-20a and miR-101a in LPS/D-GalN-induced mice and LPS-induced hepatocytes. The knockdown of miR-20a and miR-101a co-operatively alleviated ER stress of LPS-induced hepatocytes. miR-20a and miR-101a both targeted Nrf2 and the over-expression of miR-20a or miR-101a decreased Nrf2 protein level, while their silences increased Nrf2 protein level. The silence of miR-20a and miR-101a promoted Nrf2 expression and inhibited the ER stress in LPS-induced hepatocytes, while the knockdown of Nrf2 reversed these effects. The over-expression of miR-20a and miR-101a eliminated the effects of mangiferin on Nrf2 protein level and ER stress in LPS-induced hepatocytes and Nrf2 over-expression altered these trends. Our findings suggest that mangiferin alleviates ER stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis.
In recent years, with the rapid development of nano-biotechnology and biomedicine, people have provided new ideas and methods for disease diagnosis and treatment. Nano-sulfides with unique two-dimensional structures and special physicochemical properties have begun to be applied to
biology and medical field. Relevant research results show that nano-sulfides have good effects in tumor photothermal treatment, in vivo multimodal imaging, antitumor drug delivery, biosensors and tissue engineering, showing their potential application value. In view of the broad application
prospects of nano-sulfides in the field of nano-biomedicine, in the image reconstruction stage, before starting to use artificial intelligence algorithm models, first explore the application of iterative optimization algorithms in the process of magnetic resonance image reconstruction. Taking
magnetic resonance imaging as an example, for the detected ligament trauma area, we use learned an artificial intelligence model for diagnosis of multiple ligament trauma of the knee joint and postoperative femoral nerve block.
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