Multifunctional Mesoporous Silica Nanoparticles with Thermal-Responsive Gatekeeper for NIR Light-Triggered Chemo/Photothermal-Therapy.

In this work, a matrix metalloproteinase (MMP)-triggered tumor targeted mesoporous silica nanoparticle (MSN) is designed to realize near-infrared (NIR) photothermal-responsive drug release and combined chemo/photothermal tumor therapy. Indocyanine green (ICG) and doxorubicin (DOX) are both loaded in the MSN modified with thermal-cleavable gatekeeper (Azo-CD), which can be decapped by ICG-generated hyperthermia under NIR illumination. A peptidic sequence containing a short PEG chain, matrix metalloproteinase (MMP) substrate (PLGVR) and tumor cell targeting motif (RGD) are further decorated on the MSN via a host-guest interaction. The PEG chain can protect the MSN during the circulation and be cleaved off in the tumor tissues with overexpressed MMP, and then the RGD motif is switched on to target tumor cells. After the tumor-triggered targeting process, the NIR irradiation guided by ICG fluorescence can trigger cytosol drug release and realize combined chemo/photothermal therapy.

Fungal Diversity in the Soil of the Oxytropis glacialis Root System on the Qinghai-Tibet Plateau.

Because of swainonine-producing endophytic fungal, Oxytropis glacialis is one of the main poisonous weeds in the alpine grassland and desert grassland of the Qinghai-Tibet Plateau (QTP). It has a severe impact on grassland degradation on the QTP. In this manuscript, the Internally Transcribed Spacer (ITS) region of fungal communities in the soil of the O. glacialis root system was sequenced by high-throughput sequencing and analyzed by bioinformatics methods. The physical and chemical properties of the soil samples were analyzed in combination with the fungal diversity and its relationship with the soil physical and chemical factors. The results showed that the soil fungal community in the O. glacialis root system are rich in diversity in different ecological environments and are most affected by the soil pH value and organic matter. The swainonine-producing fungal Embellisia oxytropis was first detected in the soil of the O. glacialis root system. This finding provides data to support the next step in demonstrating the horizontal spread of swainone-producing fungal from O. glacialis to soil. In addition, a stable network of core flora has a facilitating effect on the formation of O. glacialis as a dominant species in alpine ecosystems.

A surface charge-switchable and folate modified system for co-delivery of proapoptosis peptide and p53 plasmid in cancer therapy.

To improve the tumor therapeutic efficiency and reduce undesirable side effects, ternary FK/p53/PEG-PLL(DA) complexes with a detachable surface shielding layer were designed. The FK/p53/PEG-PLL(DA) complexes were fabricated by coating the folate incorporated positively charged FK/p53 complexes with charge-switchable PEG-shield (PEG-PLL(DA)) through electrostatic interaction. At the physiological pH 7.4 in the bloodstream, PEG-PLL(DA) could extend the circulating time by shielding the positively charged FK/p53 complexes. After the accumulation of the FK/p53/PEG-PLL(DA) complexes in tumor sites, tumor-acidity-triggered charge switch led to the detachment of PEG-PLL(DA) from the FK/p53 complexes, and resulted in efficient tumor cell entry by folate-mediated uptake and electrostatic attraction. Stimulated by the high content glutathione (GSH) in cytoplasm, the cleavage of disulfide bond resulted in the liberation of proapoptosis peptide C-KLA(TPP) and the p53 gene, which exerted the combined tumor therapy by regulating both intrinsic and extrinsic apoptotic pathways. Both in vitro and in vivo studies confirmed that the ternary detachable complexes FK/p53/PEG-PLL(DA) could enhance antitumor efficacy and reduce adverse effects to normal cells. These findings indicate that the tumor-triggered decomplexation of FK/p53/PEG-PLL(DA) supplies a useful strategy for targeting delivery of different therapeutic agents in synergetic anticancer therapy.