Myricetin is a flavonoid with anticancer properties. This study aimed to formulate myricetin in the form of solid lipid nanoparticles (SLN), decorated with chitosan (CS) and active-targeted with folic acid (FA). After characterization, the in vitro release, cytotoxicity, antioxidant, and ability of the formulation to induce apoptosis using flow cytometry, fluorescent microscopy, and real-time qPCR were examined. Then in vivo anti-angiogenesis on chick chorioallantoic membrane (CAM) and antitumor activities on mice bearing tumor models were investigated. The present study showed that the size of 310 nm and zeta potential of + 30 mV were acceptable for oral administration. The Michaelis–Menten model fitted the drug release pattern with lag during 144 h of the study. The cytotoxicity assay showed that myricetin-SLN-CS-FA significantly killed cancer cells at the concentrations of 6.25, 12.5, 25, 50 and 100 µg/mL (*p < 0.05, **p < 0.01, and ***p < 0.001). The highest level of apoptosis was shown at the concentration of 45 µg/ml in flow cytometry, and fluorescent studies. These results showed the anticancer properties of myricetin-SLN-CS-FA in a dose-dependent manner. The real-time results also indicated that the formulation exerted its cytotoxic effect by activating apoptosis genes. The DPPH, ABTS, and FRAP studies also demonstrated the significant antioxidant properties of the myricetin-SLN-CS-FA (*p < 0.05, **p < 0.01, and ***p < 0.001). The anti-angiogenic activities of the formulations depicted in the CAM assay significantly decrease the number and length of the vessels (*p < 0.05, **p < 0.01, and ***p < 0.001), and also affect VEGF and VEGFR, genes involved in angiogenesis (**p < 0.01, and ***p < 0.001). The antitumor studies indicated the statistically significant effects of myricetin-SLN-CS-FA on reducing tumor volume (*p < 0.05 and ***p < 0.001). The H&E staining of the liver and monitoring of the animal weights also indicated the safety of the formulation. The analysis of mRNA expression in liver and tumor demonstrated that myricetin-SLN-CS-FA exerts its antitumor activities by modulating the inflammatory and oxidative responses in the tissues.

A mesoporous silica nanoparticle (MSN) coated with polydopamine (PDA) and loaded with umbelliprenin (UMB) was prepared and evaluated for its anti-cancer properties in this study. Then UMB-MSN-PDA was characterized by dynamic light scattering (DLS), Field emission scanning electron microscopy (FESEM), Transmission electron microscopy (TEM) and FTIR methods. UV-visible spectrometry was employed to study the percentage of encapsulation efficiency (EE%). UMB-MSN-PDA mediated cell cytotoxicity and their ability to induce programmed cell death were evaluated by MTT, real-time qPCR, flow cytometry, and AO/PI double staining methods. The size of UMB-MSN-PDA was 196.7 with a size distribution of 0.21 and a surface charge of −41.07 mV. The EE% was 91.92%. FESEM and TEM showed the spherical morphology of the UMB-MSN-PDA. FTIR also indicated the successful interaction of the UMB and MSN and PDA coating. The release study showed an initial 20% release during the first 24 h of the study and less than 40% during 168 h. The lower cytotoxicity of the UMB-MSN-PDA against HFF normal cells compared to MCF-7 carcinoma cells suggested the safety of formulation on normal cells and tissues. The induction of apoptosis in MCF-7 cells was indicated by the upregulation of P53, caspase 8, and caspase 9 genes, enhanced Sub-G1 phase cells, and the AO/PI fluorescent staining. As a result of these studies, it may be feasible to conduct preclinical studies shortly to evaluate the formulation for its potential use in cancer treatment.