Hepatocellular carcinoma (HCC) is one of the world’s most risky diseases due to the lack of clear and cost-effective therapeutic targets. Currently, the toxicity of conventional chemotherapeutic medications and the development of multidrug resistance is driving research into targeted therapies. The nano-biomedical field’s potential for developing an effective therapeutic nano-sized drug delivery system is viewed as a significant pharmaceutical trend for the encapsulation and release of numerous anticancer therapies. In this regard, current research is centered on the creation of biodegradable chitosan nanoparticles (CSNPs) for the selective and sustained release of bee venom into liver cancer cells. Furthermore, surface modification with polyethylene glycol (PEG) and GE11 peptide-conjugated bee venom-CSNPs allows for the targeting of EGFR-overexpressed liver cancer cells. A series of in vitro and in vivo cellular analyses were used to investigate the antitumor effects and mechanisms of targeted bee venom-CSNPs. Targeted bee venom-CSNPs, in particular, were found to have higher cytotoxicity against HepG2 cells than SMMC-7721 cells, as well as stronger cellular uptake and a substantial reduction in cell migration, leading to improved cancer suppression. It also promotes cancer cell death in EGFR overexpressed HepG2 cells by boosting reactive oxygen species, activating mitochondria-dependent pathways, inhibiting EGFR-stimulated MEK/ERK pathway, and elevating p38-MAPK in comparison to native bee venom. In hepatocellular carcinoma (HCC)-induced mice, it has anti-cancer properties against tumor tissue. It also improved liver function and architecture without causing any noticeable toxic side effects, as well as inhibiting tumor growth by activating the apoptotic pathway. The design of this cancer-targeted nanoparticle establishes GE11-bee venom-CSNPs as a potential chemotherapeutic treatment for EGFR over-expressed malignancies. Finally, our work elucidates the molecular mechanism underlying the anticancer selectivity of targeted bee venom-CSNPs and outlines therapeutic strategies to target liver cancer.

Two field experiments were carried out in a private farm located at Bangar El Sokar region -Borg Al-Arab -Alexandria, Egypt, during winter growing season of 2014/2015 to study the effects of three spacing (10, 20 and 30 cm), three Humic acid (HA) rates (control, 1000 and 2000 mg l -1 ) and three boric acid rates (control, 2.5 and 5 mg l -1 ) on the vegetative growth, seed yield and its quality of broad bean plants.The results indicated that increasing spacing between broad bean plants lead to an increase in the numbers of branchesplant -1 and poor seeds percentage. While, plant height, seed yield fed -1 (ton) and good seeds percentage characters were decreased by increasing spacing.Treated broad bean plants with humic acid increased plant height and the numbers of branches. However, using humic acid at rate 2000 mg l -1 gave the highest mean value of fresh mass plant -1 . While, increasing humic acid rate was lead to decrease the nods setting percentage. In addition to, application of 1000 mg l -1 of humic acid gave the highest mean value of the seed yield fed -1 and good seed percentage, as well as the lowest percentage of poor seeds.The results showed that the highest mean values of plant height (cm) were obtained from treated plants with 2.5 mg l -1 boric acid. Also, increasing boric acid rates up to 5 mg l -1 decreased the fresh mass of plant -1 . Whereas, the highest mean value of the earliness and nods setting percentage achieved by application 5 mg l -1 of boric acid. Increasing the boric acid rates up to 5 mg l -1 was associated with increments in the average seed yield fed -1 and the good seed percentage. In general, the highest dry seed yield fed -1 , under conditions of Bangar El Sokar region -Borg Al-Arab -Alexandria, were achieved when sowing broad bean plants at 10 cm with the application of humic acid at rate 1000 mg l -1 and foliar application of boric acid at rate 5 mg l -1 .