Supramolecular
photosensitizers based on nanosized drug delivery or combination therapy
have been proposed as a promising strategy for cancer treatment. Herein,
we screen and develop a series of multifunctional single-component,
carrier-based, natural small-molecule sterols (ergosterol, β-sitosterol,
and stigmasterol) that simultaneously possess self-assembly ability,
anticancer activity, and better biocompatibility and biodegradability
to deliver photosensitizer chlorin e6 (Ce6) for significantly combined
and safe antitumor photodynamic therapy. The resultant ergosterol–Ce6
nanodrugs (Ergo-Ce6 NPs) have enhanced reactive oxygen species (ROS)
generation by promoting type I photoreactions, while Ce6 mainly exists
in the monomer state in assembled Ergo-Ce6 NPs via intermolecular
π–π stacking and hydrophobic interactions. In addition,
with the improved water solubility and stability and higher intercellular
ROS generation, Ergo-Ce6 NPs show remarkably in vitro phototoxicity
with approximately 73% and 92% cell inhibition ratios to 4T1 and MCF-7
cancer cells at a rather low dosage of Ce6 (1 μg/mL), respectively.
Moreover, the excellent tumor targeting ability of Ergo NPs and prolonged
blood circulation ensure a quick tumor accumulation of Ergo-Ce6 NPs,
resulting in a significantly enhanced in vivo anticancer efficiency
of 86.4%, higher than that of the anticancer ability of Ergo NPs (51.0%)
or Ce6 PDT alone (59.5%). Furthermore, the resulting nanodrugs have
better biocompatibility and biodegradability and low in vivo toxicity,
and all of which ensure a safe tumor therapy. This study provides
a promising perspective to develop more natural self-assembled biological
small-molecule nanomaterials for the fabrication of novel medicinal
photosensitizers for clinical application in the future.
A field experiment was conducted to investigate the effects of powdery mildew (Blumeria graminis f. sp. Tritici, Bgt) on wheat grain at varying levels of disease severity and at different growth stages. Methods used to determine these effects included Kjeldahl determination, unidimensional polyacrylamide gel electrophoresis, dielectrophoresis combined with mass spectrometric analysis. The specific influences explored were those on prolamins and protein composition at the molecular level. Concentrations of both grain protein and prolamin in wheat increased as disease indices (DIs) of powdery mildew rose from 20 days after anthesis (DAA) to maturity. Globulin concentrations changed dynamically and significantly, especially at 25 DAA when DI was the highest. This was verified by proteomic analysis which showed globulins (such as globulin 3, globulin 3B, globulin 3C, gliadin/ avenin-like protein and triticin) being up-regulated significantly under powdery mildew stress. It was proposed that powdery mildew might indirectly affect protein accumulation in grain by influencing the regulative enzymes (including peptidylprolyl isomerase, cyclophilin A-2 and GTPase ObgE) and metabolic processes. It was speculated that the indirect increase caused by yield reduction was not the only factor causing the increase in prolamin concentration. Another factor may be the rise of expression level of molecular chaperones and enzymes relating to protein synthesis, which led to the rise in protein synthesis.
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