Bioinspired silk fibroin nano-delivery systems protect against 5-FU induced gastrointestinal mucositis in a mouse model and display antitumor effects on HT-29 colorectal cancer cells in vitro.

Colorectal cancer (CRC), is the second cause of cancer-related deaths worldwide is one of the most prevalent types of cancers. Conventional treatment continues to rely on surgery, chemotherapy, and radiotherapy, but for advanced cases, adjuvant chemotherapy remains the main approach for improving surgical outcomes and lower the disease recurrence probability. Chemotherapy-induced gastrointestinal (GI) toxicity is the main dose-limiting factor for many chemotherapeutic regimens, including 5-FU, and one of the biggest oncological challenges. Up to 40% of the patients receiving 5-FU get mucositis, 10-15% of which develop severe symptoms. In this context, our study aimed to develop a bioinspired nanosized drug delivery system as a strategy to reduce 5-FU associated side effects, such as GI mucositis. To this end, SF-based nanoparticles were prepared and characterized in terms of size and morphology, as well as in terms of in vitro antitumoral activity on a biomimetic colorectal cancer model by investigation of apoptosis, DNA fragmentation, and release of reactive oxygen species. Additionally, the capacity of the SF-based nanocarriers to offer intestinal protection against 5-FU-induced GI mucositis was evaluated in vivo using a mouse model that mimics the chemotherapy-associated gut mucositis occurring in colorectal cancer. Our studies show that silk fibroin nanoparticles efficiently deliver 5-FU to tumor cells in vitro while protecting against drug-induced GI mucositis in a mouse model.

Chrysin attenuates cardiomyocyte apoptosis and loss of intermediate filaments in a mouse model of mitoxantrone cardiotoxicity.

Chrysin (CHR) is a natural flavonoid and is present in high concentration in honey, propolis and many plant extracts. The aim of the present study was to evaluate the effects of CHR to reduce cardiomyocyte apoptosis and loss of intermediate filaments in a mouse model of mitoxantrone cardiotoxicity. Morphology of the cardiomyocytes was determined by optic and transmission electron microscopy and biochemistry methods. The expression of Bcl-2, Bax and Caspase-3 were assessed by immunofluorecence. Tunel assay was used to assess apoptosis in cardiomyocytes. In addition, the distribution of desmin protein was evaluated using immunohistochemistry. Our results show that MTX treatment significantly increased serum levels of creatine kinase isoenzyme (CK-MB), indicator of cardiac injury and withdrawn under CHR protection. Expression levels of Bcl-2 decreased, while those of Bax and caspase-3 increased following MTX treatment. 50 mg/kg of daily CHR intake reduced Bax and caspase-3 immunopositivity and restored Bcl-2 levels to a value comparable to the control. TUNEL (+) cardiomyocyte nuclei of MTX group showed typical signs of apoptosis which almost completely disappeared in response to 50 mg/kg CHR treatment. In parallel, an irregular distribution and a weak expression of desmin is associated with MTX induced cardiotoxic effects which was also restored by CHR treatment. In conclusion chrysin inhibits MTX-triggered cardiomyocyte apoptosis via multiple pathways, including decrease of the Bax/Bcl-2 ratio and caspase-3 expression along with preservation of the desmin disarray.