Construction of multi-program responsive vitamin E succinate-chitosan-histidine nanocarrier and its response strategy in tumor therapy.

Multifunctional drug delivery carriers have emerged as a promising cancer drug delivery strategy. Here, we developed a vitamin E succinate-chitosan-histidine (VCH) multi-program responsive drug carrier. The structure was characterized by FT-IR and 1H NMR spectrum, and the DLS and SEM results showed typical nanostructures. The drug loading content was 21.0 % and the corresponding encapsulation efficiency was 66.6 %. The UV-vis and fluorescence spectra demonstrated the existence of the π-π stacking interaction between DOX and VCH. Drug release experiments implied good pH sensitivity and sustained-release effect. The DOX/VCH nanoparticles could be efficiently taken up by HepG2 cancer cells and the tumor inhibition rate was up to 56.27 %. The DOX/VCH reduced the tumor volume and weight efficiently with a TIR of 45.81 %. The histological analysis results showed that DOX/VCH could effectively inhibit tumor growth and proliferation, and there was no damage to normal organs. VCH nanocarriers could combine the advantages of VES, histidine and chitosan to achieve pH sensitivity and P-gp inhibition, and effectively improve the drug solubility, targeting and lysosomal escape. Through the program response of different micro-environment, the newly developed polymeric micelles could successfully be utilized as a multi-program responsive nanocarrier system for the treatment of cancers.

Recent Advances and Progress on Melanin: From Source to Application.

Melanin is a biological pigment formed by indoles and phenolic compounds. It is widely found in living organisms and has a variety of unique properties. Due to its diverse characteristics and good biocompatibility, melanin has become the focus in the fields of biomedicine, agriculture, the food industry, etc. However, due to the wide range of melanin sources, complex polymerization properties, and low solubility of specific solvents, the specific macromolecular structure and polymerization mechanism of melanin remain unclear, which significantly limits the further study and application of melanin. Its synthesis and degradation pathways are also controversial. In addition, new properties and applications of melanin are constantly being discovered. In this review, we focus on the recent advances in the research of melanin in all aspects. Firstly, the classification, source, and degradation of melanin are summarized. Secondly, a detailed description of the structure, characterization, and properties of melanin is followed. The novel biological activity of melanin and its application is described at the end.

Germ-line mutation of NKX3.1 cosegregates with hereditary prostate cancer and alters the homeodomain structure and function.

NKX3.1, a gene mapped to 8p21, is a member of the NK class of homeodomain proteins and is expressed primarily in the prostate. NKX3.1 exerts a growth-suppressive and differentiating effect on prostate epithelial cells. Because of its known functions and its location within a chromosomal region where evidence for prostate cancer linkage and somatic loss of heterozygosity is found, we hypothesize that sequence variants in the NKX3.1 gene increase prostate cancer risk. To address this, we first resequenced the NKX3.1 gene in 159 probands of hereditary prostate cancer families recruited at Johns Hopkins Hospital; each family has at least three first-degree relatives affected with prostate cancer. Twenty-one germ-line variants were identified in this analysis, including one previously described common nonsynonymous change (R52C), two novel rare nonsynonymous changes (A17T and T164A), and a novel common 18-bp deletion in the promoter. Overall, the germ-line variants were significantly linked to prostate cancer, with a peak heterogeneity logarithm of odds of 2.04 (P = 0.002) at the NKX3.1 gene. The rare nonsynonymous change, T164A, located in the homeobox domain of the gene, segregated with prostate cancer in a family with three affected brothers and one unaffected brother. Importantly, nuclear magnetic resonance solution structure analysis and circular dichroism studies showed this specific mutation to affect the stability of the homeodomain of the NKX3.1 protein and decreased binding to its cognate DNA recognition sequence. These results suggest that germ-line sequence variants in NKX3.1 may play a role in susceptibility to hereditary prostate cancer and underscore a role for NKX3.1 as a prostate cancer gatekeeper.