Efficacy of Antineoplastic Nanocarriers on 3D Oral Cancer Spheroids.

BACKGROUND/AIM: Cancer is a leading cause of death worldwide. Conventional treatments as surgery, chemotherapy, radiotherapy, and combined therapies are commonly used. However, these therapies have several limitations and side effects. To address these issues, innovative research is being conducted on nanocarriers (NCs) functionalized with antineoplastic agents. These NCs aim to overcome limitations and improve patients' lives. However, before they can be used clinically, these NCs are primarily assessed on a lab scale to determine their efficacy. MATERIALS AND METHODS: A primary cell culture was established from a lymphoblastic neoplasm in the maxilla. After characterization, the cells were cultured in 2D to evaluate the dose-effect of nanoparticles (NPs), such as Zinc oxide (ZnO) and Magnesium oxide (MgO), as well as those of free drugs of 5-fluorouracil (5-FU) and cisplatin (Cis). Based on the results, a 3D spheroid culture was used for further study. Finally, the spheroids were histologically processed for immuno-morphological observation. RESULTS: To evaluate spheroid cell viability, we conducted an MTT assay. Treatment of cell spheroids with ZnONPs, 5-FU, and NPs conjugated with antitumor agents such as 5-FU-ZnO and Cis-ZnO decreased cell viability by >25%, >60% and >10% and <20% at a concentration of 0.06, 0.015 and 0.015 & 0.03 mg/ml, respectively. CONCLUSION: Nanoparticles conjugated with antitumor agents showed promising antineoplastic effects on both 2D and 3D cell cultures. However, the efficacy of the nanoparticles varied between the different models. This highlights the importance of selecting appropriate in vitro culture models for the evaluation of biomedical agents.

Experimental vaccination in rabbits using the peptide RmS-17 antigen reduces the performance of a Mexican Rhipicephalus microplus tick strain.

The tick vector Rhipicephalus microplus is considered one of the main problems in cattle production in tropical and subtropical regions. Anti-tick vaccines may form an alternative tick control method to the use of acaricides, and tick salivary proteins, such as Serpins, may be valuable as target antigens for developing anti-tick vaccines. In this study, we synthesized a recombinant peptide derived from Serpin RmS-17 protein using an Escherichia coli expression system and characterized the efficacy of the peptide RmS-17 for the control of R. microplus females infesting rabbits. Twelve New Zealand white rabbits were assigned to three experimental groups and vaccinated with three subcutaneous doses of the peptide RmS-17, recombinant R. microplus Bm86 antigen, and adjuvant/saline alone. The tick challenge was conducted with 120 R. microplus adults (60 females and 60 males) per animal, with the ticks placed inside a cotton sleeve glued to the back of the rabbit. Serum antibody levels (IgG) were assessed by ELISA and confirmed by Western blot; also, the reproductive performance of R. microplus was determined. The results showed that experimental vaccination in rabbits using the peptide RmS-17 antigen had a vaccine efficacy of 79% based on reductions in adult tick number, oviposition, and egg fertility compared to control animals. The peptide RmS-17 vaccinated rabbits developed a strong humoral immune response expressed by high anti-pRmS-17 IgG levels, and the Western blot analysis confirmed that it is immunogenic. The efficacy for the Bm86 vaccine was 62%, which is within the range of efficacy reported previously for Bm86 vaccine. The negative correlation between antibody levels and reduction in tick number strongly suggests that the effect of the vaccine was the result of the antibody response in vaccinated rabbits. In conclusion, this is the first study to evaluate the efficacy of the peptide RmS-17 against R. microplus tick infestation and show it to be immunogenic and protective in a rabbit model.

Protective efficacy of the peptide Subolesin antigen against the cattle tick Rhipicephalus microplus under natural infestation.

The cattle tick Rhipicephalus microplus affect animal health, welfare, and cattle production in tropical and subtropical zones of the world. Anti-tick vaccines have been an effective alternative for cattle tick control instead of traditional chemical products. To date, Subolesin antigen has shown efficacy for the control of tick infestation in cattle, and previous studies showed that one peptide derived from this protein has demonstrated to elicit a strong and specific humoral immune response. Based on these findings, herein we characterized the efficacy of the peptide Subolesin for the control of cattle tick, R. microplus infestation under field conditions. Twenty-four female calves were assigned to four experimental groups and immunized with three subcutaneous doses of the peptide Subolesin, Bm86, both antigens (dual vaccine) and adjuvant/saline alone, respectively. Serum antibody levels (IgG) were assessed by ELISA and confirmed by Western blot; also, reproductive performance of naturally infested R. microplus was determined. The results showed that immunizations with the experimental antigens reduced tick infestations with vaccine's efficacy of 67 % (peptide Subolesin), 56 % (Bm86), and 49 % (dual vaccine) based on adult tick numbers, oviposition, and egg fertility between vaccinated and control animals. Peptide Subolesin-immunized calves developed a strong humoral immune response expressed by high anti-pSubolesin IgG levels, and the Western blot analysis confirmed that it is immunogenic. Cattle receiving Bm86 and dual vaccine showed less protection, although Bm86 was within the range reported previously. The negative correlation between antibody levels and reduction of naturally infested R. microplus strongly suggested that the effect of the vaccine was the result of the antibody response in immunized cattle. In conclusion, it was demonstrated that the peptide Subolesin induced a specific immune response in cattle under field conditions, resulting in reduced R. microplus populations in subsequent generations. Finally, integrated tick control must consider anti-tick vaccines as a cost-effective, sustainable, and successful tool for controlling cattle tick infestations.