Nanoparticle-based cancer immunotherapy is considered a novel and promising therapeutic strategy aimed at stimulating host immune responses against tumors. To this end, in the present study, mannan-decorated polylactic-co-glycolic acid (PLGA) nanoparticles containing tumor cell lysate (TCL) and poly riboinosinic polycytidylic acid (poly I:C) were used as antigen delivery systems to immunize breast tumor-bearing Balb/c mice. PLGA nanoparticles were fabricated employing a double emulsion solvent evaporation method. The formation of spherical and uniform nanoparticles (NPs) ranging 150-250 nm was detected by field emission scanning electron microscopy (FESEM) and dynamic light scattering (DLS). Four nanoformulation were used to treat mice and vaccination-induced immunological responses. Tumor regression and overall survival rate were evaluated in four experimental groups. Tumor cell lysate and poly I:C loaded mannan-decorated nanoparticles (TCL-Poly I:C) NP-MN caused a significant decrease in tumor growth and 2- to 3-fold improvement in survival times of the treated mice. The NPs with or without mannan decoration elicited stronger responses in terms of lymphocyte proliferation, delayed-type hypersensitivity and CD107a expression. Moreover, our data indicated that the production of IFN-γ and IL-2 increased while the production of IL-4 and IL-10 decreased in splenocytes culture supernatants. In the pathological evaluations, we found that necrosis and immune cells infiltration rate in the tumor tissue of the treated mice was elevated, while tumor cellularity and lung metastases significantly decreased in particular in the group that received (TCL-Poly I:C) NP-MN. Altogether, our findings suggested that the mannan-decorated PLGA NPs antigen delivery system had significant anti-tumor effects against the murine model of breast cancer and it could be considered as a step forward to human breast cancer immunotherapy.

Hesperidin, a phytochemical renowned for its therapeutic effects including anticancer, antioxidant, and anti-inflammatory properties, encounters a significant limitation in its application due to its low bioavailability and restricted solubility in water. To surmount these challenges, we employed a spontaneous emulsification method to produce hesperidin nanoparticles. These nanoparticles, averaging 197.2 ± 2.8 nm, exhibited uniform dispersion (polydispersity index: 0.13), a zeta potential (ZP) of −28 mV, encapsulation efficiency of 84.04 ± 1.3%, and demonstrated stable and controlled release across various environments. Assessment of the nanoemulsions stability revealed remarkably high stability levels. Cytotoxicity evaluations (3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl-2-H-tetrazolium bromide, neutral red, trypan blue, and lactate dehydrogenase) indicated that cancer cell viability following treatment with hesperidin nanoemulsion was concentration and time-dependent, significantly lower compared to cells treated with free hesperidin. The colony formation assay and cell morphology evaluation further corroborated the heightened efficacy of hesperidin in its nano form compared to the free form. In summary, hesperidin nanoparticles not only exhibited more potent anticancer activity than free hesperidin but also demonstrated high biocompatibility with minimal cytotoxic effects on healthy cells. These findings underscore the potential for further exploration of hesperidin nanoparticles as an adjunctive therapy in prostate cancer therapy.

Natural origin therapeutic agents have recently gained attention as a promising cancer treatment approach. However, achieving effective therapeutic results depends on improving the pharmacokinetic properties of these compounds using new delivery systems. In this study, the simultaneous encapsulation of berberine and hesperidin in poly(lactic-co-glycolic acid)(PLGA) nanoparticles utilizing the double emulsion-solvent evaporation technique and the evaluation of their effects on the viability and induction of apoptosis in prostate cancer cells were investigated. The produced nanoparticles were characterized in terms of size, dispersion index, morphology, FT-IR analysis, encapsulation efficiency, and drug release profile. Prostate cancer cells (LNCaP) were cultured and treated with various concentrations of hesperidin and berberine in nanoencapsulation and free forms. The results showed that all produced nanoparticles had an average diameter below 200 nm, a uniform size distribution below 0.1, and a favorable encapsulation efficiency. According to the MTT test results, the application of nanoparticles resulted in a significant reduction in cell viability compared to the free form, which occurred in a dose-dependent manner. Flow cytometry and qRT-PCR analysis showed that hesperidin and berberine in nano form and combination had the greatest anti-cancer effects. In the comparison between hesperidin and berberine, too, berberine showed stronger anti-proliferative and apoptotic effects than hesperidin. The findings from the LDH and clonogenic assays also confirmed the apoptotic and cytotoxic effects of hesperidin and berberine in both nano form and combination. These findings indicate that berberine and hesperidin in combination, especially in nano form, hold significant promise as a treatment approach for prostate cancer.

Chloroform (CH) is considered an urgent environmental pollutant that leads to critical health effects. This investigation was carried out to verify the involvement of serum cytokines in the hepatic dysfunction induced by single exposure to CH in laboratory rats. Eighteen adult male laboratory rats were separated into three groups of eight rats each. Control (CON) group included animals without any treatment, while the rest of the two groups were administrated trichloromethane at a dose of 477 mg/kg , orally then sacrificed after 1 day (CH-1) and 7day (CH-7) post-exposure. The results indicated that single-dose exposure induced liver dysfunction through significant elevation of serum activities of hepatic enzymes compared with unexposed control rats. Furthermore, chloroform intoxication caused a significant time-dependent rise in concentrations of some pro-inflammatory cytokines in serum of exposed rats. In conclusion, a single high dose of chloroform causes liver dysfunction and promotes the response of pro-inflammatory cytokines in rats.