Melittin, a main component of bee venom, is a cationic amphiphilic peptide with a linear α-helix structure. It has been reported that melittin can exert pharmacological effects, such as antitumor, antiviral and anti-inflammatory effects in vitro and in vivo. In particular, melittin may be beneficial for the treatment of diseases for which no specific clinical therapeutic agents exist. Melittin can effectively enhance the therapeutic properties of some first-line drugs. Elucidating the mechanism underlying melittin-mediated biological function can provide valuable insights for the application of melittin in disease intervention. However, in melittin, the positively charged amino acids enables it to directly punching holes in cell membranes. The hemolysis in red cells and the cytotoxicity triggered by melittin limit its applications. Melittin-based nanomodification, immuno-conjugation, structural regulation and gene technology strategies have been demonstrated to enhance the specificity, reduce the cytotoxicity and limit the off-target cytolysis of melittin, which suggests the potential of melittin to be used clinically. This article summarizes research progress on antiviral, antitumor and anti-inflammatory properties of melittin, and discusses the strategies of melittin-modification for its future potential clinical applications in preventing drug resistance, enhancing the selectivity to target cells and alleviating cytotoxic effects to normal cells.
19 June 2018 in ACS Applied Materials & Interfaces
Background: Adipose-derived mesenchymal stem cells (ADMSCs) have attracted widespread interest as cell-based tissue repair systems. To obtain adequate quantities of ADMSCs for therapeutic applications, extensive in vitro expansion is required. However, under current two-dimensional (2D) approaches, ADMSCs rapidly undergo replicative senescence, and cell growth is impeded and stem cell properties are eliminated by mechanisms that are poorly understood. These issues limit the extensive applications of ADMSCs. In this study, we investigated senescence-related changes in mesenchymal stem cells (MSCs) isolated from human adipose tissue in 2D and three-dimensional (3D) cultures.Methods: We studied cell growth over a given period (21 days) to determine if modes of culture were associated with ADMSC senescence. ADMSCs were isolated from healthy females by liposuction surgery and then were grown in 2D and 3D cultures. The cell morphology was observed during cell culture. Every other time of culture, senescence-associated β-galactosidase (SA-β-gal) expression, cell viability, proliferation, and differentiation potential of ADMSCs from 2D and 3D cultures were detected. Also, senescence- and stemness-related gene expression, telomere length, telomerase activity, and energy metabolism of ADMSCs for different culture times were evaluated.Results: With long-term propagation, we observed significant changes in cell morphology, proliferation, differentiation abilities, and energy metabolism, which were associated with increases in SA-β-gal activity and decreases in telomere length and telomerase activity. Notably, when cultured in 3D, these changes were improved.Conclusions: Our results indicate that 3D culture is able to ameliorate senescence-related changes in ADMSCs.
The NIR dye cyanine (Cy) is one of the most significant phototherapy agents (PTAs) due to its strong NIR absorbance, high thermal conversion capacity and good safety. However, its clinic application is seriously limited owing to its inherent properties as an organic dye, including low solubility, poor selectivity, and fast clearance. Thus, herein, we embed Cy into the zeolitic imidazolate framework-8 (Cy@ZIF-8) for antitumor photothermal therapy (PTT). The obtained Cy@ZIF-8 NPs not only have good water solubility and excellent photostability, but also exhibit strong NIR absorbance and great photothermal conversion efficiency. Especially, the Cy@ZIF-8 NPs efficaciously inhibit tumor growth and possess outstanding NIR imaging capacity both in vitro and in vivo. This work demonstrates the theranostic value of Cy@ZIF-8 NPs for imaging-guided PTT therapy, and also encourages the further study of other PTAs@ZIF-8 composites for better anticancer PTT.
A sandwich-type electrochemical biosensor was successfully constructed for the sensitive detection of pathogenic bacteria. In this biosensor platform, methylene blue (MB) organic–inorganic nanocomposites (MB@MI) were synthesized from magainin I (MI, antimicrobial peptide specific to Escherichia coli O157:H7), Cu3(PO4)2 and MB via a one-pot method, and were explored as a novel electrochemical signal label of biosensors generating amplified electrochemical signals by differential pulse voltammetry (DPV). E. coli O157:H7 specifically sandwich bound to the aptamers on the electrode surface and MB@MI nanocomposites, and the changes in the current signal generated on the electrode surface were used for the quantitative determination of E. coli O157:H7. Under optimum conditions, the proposed biosensor showed excellent performance with a wide linear range of 102–107 CFU mL−1 and a low detection limit of 32 CFU mL−1, featuring favorable selectivity, repeatability and stability. According to the experiments conducted on real samples, the proposed approach is capable of detecting pathogenic bacteria in clinical diagnostics.
1 December 2018 in Bioorganic & Medicinal Chemistry Letters