Intracellular Fate of Nanoparticles with Polydopamine Surface Engineering and a Novel Strategy for Exocytosis-Inhibiting, Lysosome Impairment-Based Cancer Therapy.

Polydopamine (PDA) coating as a bioinspired strategy for nanoparticles (NPs) has been extensively applied in cancer theranostics. However, a cellular-level understanding of nano-biointeraction of these PDA-coated NPs (PDNPs), which drives the fate of them and acts as a critical step to determine their efficacy, still remains unknown. Herein, we utilized the representative mesoporous silica NPs (MSNs) to be coated with PDA and study their nano-bioactivities in cancer cells. HeLa cell line was utilized as a model in this study. The PDNPs were discovered to be internalized through three specific pathways, that is, Caveolae-, Arf6-dependent endocytosis, and Rab34-mediated macropinocytosis (55%, 20% and 37% of uptake inhibition by nystatin, Arf6 knockdown, and rottlerin, respectively). Autophagy-mediated accumulation of PDNPs in lysosomes was observed and the formed PDA shells shedded in the lysosomes. Almost 40% of the NPs were transported out of cells via Rab8/10- and Rab3/26-mediated exocytosis pathways at our tested level. On the basis of these results, a novel combined cancer treatment strategy was further proposed using drug-loaded MSNs-PDA by (i) utilizing naturally intracellular mechanism-controlled PDA shedding for organelle-targeted release of drugs in lysosomes to generate lysosome impairment and (ii) blocking the demonstrated exocytosis pathways for enhanced therapeutic efficacy.

A new species of the genus Sovia (Lepidoptera: Hesperiidae) from Qinling-Daba Mountains of China.

In this paper, a new species Sovia lii spec. nov. is described from Qinling-Daba Mountains in S. Gansu province and S. Shaanxi province, W. China. Variability of wing pattern, differences with its similar congeners and some biological information of this new taxon are introduced. External variability of Sovia lucasii, which is discovered from Shaanxi for the first time and is sympatric with the new species there, is illustrated and discussed. A brief analysis of the distributional pattern of the genus Sovia is provided. A key to the genus is given.

Rapamycin and FK506 derivative TH2849 could ameliorate neurodegenerative diseases through autophagy with low immunosuppressive effect.

Autophagy is an essential cellular process concern with cellular homeostasis down-regulated by mTOR, whose activity can be modulated by rapamycin, a kind of lipophilic macrolide antibiotic, through forming a complex with immunophilin FKBP12 essential for mTOR regulation to induce autophagy. Therefore, rapamycin is normally used as a neuron protective agent. The immunophilin FKBP12 binding ligand FK506 is well known as an immunosuppressive agent by inhibiting the calcineurin expression. In this study, we synthesized a series of modified compounds based on the FKBP12 binding moiety to as same as the binding structure of rapamycin and FK506 particularly. We removed the other binding regions of the complex that has the property of immunosuppression. We found that a novel small molecule named TH2849 from these derivative compounds has a significant binding connection with mTOR by comparing to calcineurin. The effects of TH2849 on calcineurin/NFAT were not as significant as FK506, and weak effects on IL2/p34cdc2 /cyclin signaling pathway were also found. Moreover, TH2849 also shows mitochondrial protective effect through stabilizing the mitochondrial structure and transmembrane potential (ΔΨm) and could rescue dopaminergic neurons in MPTP-treated zebrafishes as well as mice models with less immunosuppressive effect. Our present study shows that TH2849 works as a neuroprotective agent possibly by inducing autophagy and low immunosuppressive effect.

Topical Use of Quercetin-Loaded Chitosan Nanoparticles Against Ultraviolet B Radiation.

Ultraviolet radiation is a major risk factor for human skin damage, especially solar ultraviolet-B (UVB) which can induce inflammation, photoaging, and skin cancer. Quercetin (Qu), one of flavonoid family members, has showed protective effects against UVB radiation. However, its application for topical use is limited by low hydrophilicity and poor percutaneous absorption. Herein, we found that Qu, if entrapped into TPP-Chitosan nanoparticles (TCs), can be efficiently uptake by HaCaT cells and easily permeate through the epidermis layer, meanwhile display better stability and low cytotoxicity. We also found that Qu-loaded TCs (QTCs) could notably enhance the effect of Qu on inhibiting the NF-kB/COX-2 signaling pathway as well as ameliorating the skin edema caused by UVB radiation. Therefore, this study provided a method to get rid of Qu's low hydrophilicity, enhance its percutaneous absorption and retention in the skin, and further improve its anti-UVB effect, and demonstrated that Qu-loaded chitosan nanoparticles can be used as the therapeutic agent for topical use against UVB radiation.