Transforming Passive into Active: Multimodal Pheophytin-Based Carbon Dots Customize Protein Corona to Target Metastatic Breast Cancer.

Formation of protein corona on nanomaterials surface in vivo is usually considered as an unpredictable event for a predefined targeted delivery system for malignant cancers. In most situations, these protein coronas substantially change targeting efficiency or even cause adverse reactions which both hinder the clinical translation of the cargo-delivery systems. Active customization of protein corona onto nanomaterials surfaces can benefit their biomedical performances and open up new opportunities in construction of targeted delivery systems. Herein, lipid-PEG/pheophytin carbon dots (LPCDs) are prepared from natural chlorophyll and integrate seamlessly with positron emission tomography imaging, near-infrared fluorescence imaging, and photodynamic therapy capacity. In vitro measurements demonstrate that the LPCDs can actively absorb apolipoproteins into the protein corona to enhance their uptakes in breast cancer cells. In vivo studies confirm that LPCDs can give accurate delineation of metastatic breast cancer foci from surrounding normal tissues with multimodal biomedical functions. The feasibility of using LPCDs as a multimodal imaging and cancer-targeting nanoplatform may provide impetus for developing precise yet facile protein corona-targeted delivery systems for future clinical practice.

Hydroalcoholic extract of Tagetes minuta L. inhibits inflammatory bowel disease through the activity of pheophytins on the NF-κB signalling pathway.

ETHNO-PHARMACOLOGICAL RELEVANCE: Species of the genus Tagetes are well known for their anti-inflammatory properties. Tagetes minuta "Huacatay" is an endemic species of South America that has been used in traditional medicine since ancient times as a remedy for stomach and intestinal discomfort. AIM OF THE STUDY: The aim of this study is to investigate the anti-inflammatory activity of the aqueous and hydroalcoholic extracts of the Huacatay, identifying the compounds responsible for this activity. MATERIALS AND METHODS: Anti-inflammatory activity of the compounds, fractions and extracts was evaluated in Hs 746T (stomach), HIEC-6 (intestine) and THP-1 (monocytes peripheral blood) cells by measuring their inhibitory capacity against the NF-κB production. RESULTS: Aqueous and hydroalcoholic extracts of Tagetes minuta displayed anti-inflammatory activity in vitro, the hydroalcoholic extract being the most active (IC50 between 59.72 and 66.42 µg/mL) in all cell lines. Bio-guided hydroalcoholic extract fractionation led to the isolation and characterisation of two pheophytins, pheophytin a (1) and 132-hydroxy pheophytin a (2). Both compounds inhibited the production of NF-κB with IC50 values in the low micromolar range, with an IC50 between 12.32 and 16.01 µM for compound 1 and 7.91-9.87 µM for compound 2. CONCLUSIONS: The two pheophytins isolated in this study inhibit the production of NF-κB, thus showing that the traditional anti-inflammatory use of Tagetes minuta can be proved through pharmacological assays. This contributes to understanding the anti-inflammatory activity of the Huacatay extracts and their use in the treatment of stomach and intestinal discomfort.

Chlorophyll revisited: anti-inflammatory activities of chlorophyll a and inhibition of expression of TNF-α gene by the same.

In view of the folklore use of green leaves to treat inflammation, the anti-inflammatory property of chlorophylls and their degradation products were studied. Chlorophyll a and pheophytin a (magnesium-free chlorophyll a) from fresh leaves showed potent anti-inflammatory activity against carrageenan-induced paw edema in mice and formalin-induced paw edema in rats. Chlorophyll a inhibited bacterial lipopolysaccharide-induced TNF-α (a pro-inflammatory cytokine) gene expression in HEK293 cells, but it did not influence the expression of inducible nitric acid synthase and cyclooxygenase-2 genes. Chlorophyll b only marginally inhibited both inflammation and TNF-α gene expression. But both chlorophyll a and chlorophyll b showed the same level of marginal inhibition on 12-O-tetradecanoyl-phorbol-13-acetate-induced NF-κB activation. Chlorophylls and pheophytins showed in vitro anti-oxidant activity. The study shows that chlorophyll a and its degradation products are valuable and abundantly available anti-inflammatory agents and promising for the development of phytomedicine or conventional medicine to treat inflammation and related diseases.

Potent suppressive effect of a Japanese edible seaweed, Enteromorpha prolifera (Sujiao-nori) on initiation and promotion phases of chemically induced mouse skin tumorigenesis.

Potent antigenotoxic and anti-tumor promoting activities of a Japanese edible seaweed, Enteromorpha prolifera (Sujiao-nori in Japanese) were previously identified using an in vitro cell culture experiment (Y. Okai, K. Higashi-Okai, S. Nakamura, Y. Yano, S. Otani, Cancer Lett. 87 (1994) 25-32). However, in vivo anti-carcinogenic activity of this seaweed has not been elucidated until now. In the present study, the anticarcinogenic activity of E. prolifera was analyzed using an initiation and promotion model experiment of mouse skin tumorigenesis caused by 7,12-dimethylbenz[a]anthracene (initiator) and 12-O-tetradecanoylphorbol-13-acetate (promoter). (1) Application of the extract of E. prolifera prior to the treatment with a tumor initiator or promoter caused a significant suppression against skin tumorigenesis, and the combined application of the extract prior to both treatments with initiator and promoter exhibited much stronger suppression against the same skin tumorigenesis. (2) As a possible active principle for the anticarcinogenic activity of the extract, we propose a chlorophyll-related compound, pheophytin-a, which has been recently identified in the extract of this alga as an antigenotoxic substance (Y. Okai, K. Higashi-Okai, J. Sci. Food Agric. 74 (1997) 531-535), and showed significant suppressive effects in the same tumorigenesis experiment. These results suggest that E. prolifera has a potent suppressive activity against chemically induced mouse skin tumorigenesis through the suppression at the initiation and promotion phases, and that pheophytin-a might be partially associated with the in vivo anticarcinogenic activity.