The blood-brain barrier (BBB), a dynamic and complex barrier formed by endothelial cells, can impede the entry of unwanted substances – pathogens and therapeutic molecules alike – into the central nervous system (CNS) from the blood circulation. Taking into account the fact that CNS-related diseases are the largest and fastest growing unmet medical concern, many potential protein- and nucleic acid-based medicines have been developed for therapeutic purposes. However, due to their poor ability to cross the BBB and the plasma membrane, the above-mentioned bio-macromolecules have limited use in treating neurological diseases. Finding effective, safe, and convenient ways to deliver therapeutic molecules into the CNS is thus urgently required. In recent decades, much effort has been expended in the development of drug delivery technologies, of which cell-penetrating peptides (CPPs) have the most promising potential. The present review covers the latest advances in CPP delivery technology, and provides an update on their use in CNS-targeted drug delivery.
SnO2-Fe2O3 interconnected nanotubes were obtained by combining the single nozzle electrospinning and thermal treatment methods. The results of scanning electron microscopy revealed the special structure of ruptures and interconnected nanotubes in the as-prepared materials. The toluene sensing test results of SnO2-Fe2O3 interconnected nanotubes show that SnO2-Fe2O3 interconnected nanotubes possess excellent toluene gas-sensing properties. The sensitivity of detecting limit (50 ppb) is 2.0 at the optimum operating temperature of 260 °C. The response and recovery times to 1 ppm toluene are about 5 and 11 s, respectively. Moreover, the SnO2-Fe2O3 interconnected nanotube gas sensors exhibit the remarkable selectivity to toluene, and good long-term stability.
Mitochondria are promising targeting organelles for anticancer strategies; however, mitochondria are difficult for antineoplastic drugs to recognize and bind. Mitochondria-penetrating peptides (MPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo into mitochondria. MPPs have combined or delivered a variety of antitumor cargoes and obviously inhibited the tumor growth in vivo and in vitro. MPPs create new opportunities to develop new treatments for cancer. Areas covered: We review the target sites of mitochondria and the target-penetration mechanism of MPPs, different strategies, and various additional strategies decorated MPPs for tumor cell mitochondria targeting, the decorating mattes including metabolism molecules, RNA, DNA, and protein, which exploited considered as therapeutic combined with MPPs and target in human cancer treatment. Expert opinion/commentary: Therapeutic selectivity that preferentially targets the mitochondrial abnormalities in cancer cells without toxic impact on normal cells still need to be deepen. Moreover, it needs appropriate study designs for a correct evaluation of the target delivery outcome and the degradation rate of the drug in the cell. Generally, it is optimistic that the advances in mitochondrial targeting drug delivery by MPPs plasticity outlined here will ultimately help to the discovery of new approaches for the prevention and treatment of cancers.
Cell-penetrating peptide (CPP) based delivery have provided immense potential for the therapeutic applications, however, most of nonhuman originated CPPs carry the risk of possible cytotoxicity and immunogenicity, thus may restricting to be used. Here, we describe a novel human-derived CPP, denoted hPP10, and hPP10 has cell-penetrating properties evaluated by CellPPD web server, as well as In-Vitro and In-Vivo analysis. In vitro studies showed that hPP10-FITC was able to penetrate into various cells including primary cultured cells, likely through an endocytosis pathway. And functionalized macromolecules, such as green fluorescent protein (GFP), tumor-specific apoptosis inducer Apoptin as well as biological active enzyme GCLC (Glutamate-cysteine ligase, catalytic subunit) can be delivered by hPP10 in vitro and in vivo. Collectively, our results suggest that hPP10 provide a novel and versatile tool to deliver exogenous proteins or drugs for clinical applications as well as reprogrammed cell-based therapy.
Selective interruption of Hes1 or maintenance of Hes1 at a reasonable level decreases the promoter activities of α-SMA and COL1α2, and these conditions may provide an anti-fibrotic strategy against hepatic fibrosis.
Induced pluripotent stem (iPS) cells were created from mouse fibroblasts by induced expression
of Yamanaka factors, Oct3/4, Sox2, Klf4, and c-Myc. This technique has quickly resulted in an exponential
increase in the amount of pluripotency studies, and has provided a valuable tool in regenerative medicine. At
the same time, many methodologies to generate iPS cells have been reported, and are comprised mainly of
viral methods and non-viral methods. Although viral methods may not be applicable for clinical applications, various nonviral
methods have been reported in recent years, including DNA vector-based approaches, transfection of mRNA, transduction
of reprogramming proteins, and use of small molecule compounds. This review summarizes and evaluates these
non-viral methods.
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