The role of green synthesis metal and metal oxide nanoparticles in oral cancer therapy: a review

Introduction: According to National Cancer Institute, a total of 16,290 new cases of oral cancer are estimated in Brazil in 2017, with 12,370 new cases of oral cavity cancer in men and 4,010 in women corresponding to an estimated risk of 11.54 cases new for every 100 thousand men and 3.92 for each 100 thousand women. In this sense, oral cancer therapy is associated with a multitude of head and neck sequelae including hyposalivation, increased risk of tooth decay, osteoradionecrosis of the jaw, radiation fibrosis syndrome, mucositis, chemotherapy-induced neuropathy, dysgeusia, dysphagia, mucosal lesions, trismus, and infections. Objective: The present study addressed the main considerations about maxillofacial cancer and possible treatments based on the literary findings through a narrative and integrative review. Methods: Clinical studies with qualitative and/or quantitative analysis were included, following the rules of the systematic review-PRISMA. Results and Conclusion: A total of 86 articles were found involving "Bucomaxillofacial Treatment in Cancer Patients". A total of 29 articles were evaluated in full, and 24 were included and discussed in this study. Oral cancer or oral carcinoma is a chronic, complex, multifactorial pathology resulting from the interaction of intrinsic and extrinsic factors that leads to an imbalance in the process of cell proliferation and growth control. There is an association between periodontal disease, nutritional status parameters, and antimicrobial protein levels, in the case of erythroplakia, 70.0 % to 95.0 % of these lesions are cancerous at the time of initial biopsy or will progress to cancer. In invasive squamous cell carcinoma, cancer cells have penetrated deeper layers of the oral cavity and oropharynx. Therefore, preparing a comprehensive treatment plan for cancer patients is essential to help minimize the risks of developing these oral and dental complications. In addition, dentists should consider a patient's ongoing cancer therapy for those patients who come to the dentist while receiving cancer treatment.

Introduction: According to the National Cancer Institute, a total of 16,290 new cases of oral cancer were estimated in Brazil in 2017, with 12,370 new cases of oral cavity cancer in men and 4,010 in women corresponding to an estimated risk of 11.54 cases new for every 100 thousand men and 3.92 for each 100 thousand women. In this sense, oral cancer therapy is associated with a multitude of head and neck sequelae including hyposalivation, increased risk of tooth decay, osteoradionecrosis of the jaw, radiation fibrosis syndrome, mucositis, chemotherapy-induced neuropathy, dysgeusia, dysphagia, mucosal lesions, trismus, and infections. Objective: It was to present the main clinical approaches to dental treatment in cancer patients through a systematic review. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from November 2023 to February 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 156 articles were found, 58 articles were evaluated in full and 29 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 32 studies with a high risk of bias and 20 studies that did not meet GRADE and AMSTAR-2. Most studies did not show homogeneity in their results, with X2=61.8%>50%. It was concluded that preparing a comprehensive treatment plan for cancer patients is essential to help minimize the risks of developing these oral and dental complications. Additionally, dentists should consider the patient's ongoing oncology therapy for those patients who see the dentist while receiving cancer treatment.

Oral cancer early detection: What will it take?

Cancer is a leading cause of death worldwide, but advances in treatment, early detection, and prevention have helped to reduce its impact. To translate cancer research findings into clinical interventions for patients, appropriate animal experimental models, particularly in oral cancer therapy, can be helpful. In vitro experiments using animal or human cells can provide insight into cancer's biochemical pathways. This review discusses the various animal models used in recent years for research and clinical intervention in oral cancer, along with their advantages and disadvantages. We highlight the advantages and limitations of the used animal models in oral cancer research and therapy by searching the terms of animal models, oral cancer, oral cancer therapy, oral cancer research, and animals to find all relevant publications during 2010‐2023. Mouse models, widely used in cancer research, can help us understand protein and gene functions in vivo and molecular pathways more deeply. To induce cancer in rodents, xenografts are often used, but companion animals with spontaneous tumours are underutilized for rapid advancement in human and veterinary cancer treatments. Like humans with cancer, companion animals exhibit biological behaviour, treatment responses, and cytotoxic agent responses similar to humans. In companion animal models, disease progression is more rapid, and the animals have a shorter lifespan. Animal models allow researchers to study how immune cells interact with cancer cells and how they can be targeted specifically. Additionally, animal models have been extensively used in research on oral cancers, so researchers can use existing knowledge and tools to better understand oral cancers using animal models.

There are various physical and chemical techniques for the synthesis of nanoparticles. However, the green synthesis of nanoparticles, particularly the biosynthesis of metal nanoparticles using plants, has garnered significant interest from researchers worldwide. In addition to being an environmentally safe technique, green synthesis offers numerous biological applications, including antifungal, antiviral, antibacterial, wound healing, antioxidant, and antitumor properties. Ephedra (ma‐huang) is a valuable resource for phytochemical components that have pharmaceutical effects, such as phenolic compounds, reducing sugars, flavonoids, alkaloids, tannins, and saponins. These compounds, which possess antimicrobial and antioxidant effects, have attracted attention as reducing and stabilizing agents to facilitate the synthesis of metallic and metal oxide nanoparticles. Various metallic nanoparticles, including silver, gold, copper, selenium, arsenic, and zinc, have been synthesized using Ephedra extracts, demonstrating antibacterial, antifungal, and antioxidant properties. This study aims to investigate the green synthesis of metal nanoparticles utilizing different species of the Ephedra plant and to explore their biological applications.

Oral cavity contains numerous microorganisms. Among them, some are pathogenic and cause infections. Hence to control and prevent such infections, a lot of research has been conducted on different materials using various advanced techniques. Nanotechnology and nanoscience have emerged in the recent years exploring the antimicrobial effects of metal nanoparticles. Metal oxide nanoparticles have shown good results against microorganisms. Distinct physical, chemical and biologic properties of metallic oxide nanoparticles make them efficient antimicrobial agents. Both the size and high surface to volume ratio have been considered as the reason for their microbicidal efficacy. Metallic oxide nanoparticles show high durability and less cell toxicity compared to organic nanoparticles. And this positive response of metallic oxide nanoparticles make their use in medical and dental fields more promising. Most of the infections of oral cavity are fungal, bacterial or viral. In dentistry, microorganisms are believed to cause failures of many treatment by causing infections. To achieve a long-term success of treatment rendered, various possibilities have been studied. Application of this nanotechnology in dentistry termed as nano dentistry, has brought many effective changes in the control of oral infections as well as changes in the dental materials. Various metallic nanoparticles like silver nanoparticles, zinc oxide nanoparticles etc., have been used as well as modified in order to apply in dentistry. Many researches have been carried out by incorporating metallic oxide nanoparticles with dental materials which have shown excellent antimicrobial effectiveness. This review focuses on metal and metallic oxide nanoparticles and their effectiveness as antimicrobials and their various applications in dental field. KEY WORDS Nanoparticles, Antimicrobials, Metallic Oxides, Dental Materials, Dentistry

Distinct Epidemiologic Characteristics of Oral Tongue Cancer Patients

Green synthesis (GS) is a vital method for producing metal nanoparticles with antimicrobial properties. Unlike traditional methods, green synthesis utilizes natural substances, such as plant extracts, microorganisms, etc., to create nanoparticles. This eco-friendly approach results in non-toxic and biocompatible nanoparticles with superior antimicrobial activity. This paper reviews the prospects of green synthesis of metal nanoparticles of silver (Ag), copper (Cu), gold (Au) and metal oxide nanoparticles of zinc (ZnO), magnesium (MgO), cobalt (Co3O4), and titanium (TiO2) using plant extracts from tissues of leaves, barks, roots, etc., antibacterial mechanisms of metal and metal oxide nanoparticles, and obstacles and factors that need to be considered to overcome the limitations of the green synthesis process. The clean surfaces and minimal chemical residues of these nanoparticles contribute to their effectiveness. Certain metals exhibit enhanced antibacterial properties only in GS methods due to the presence of bioactive compounds from natural reducing agents such as Au and MgO. GS improves TiO2 antibacterial properties under visible light, while it would be impossible without UV activation. These nanoparticles have important antimicrobial properties for treating microbial infections and combating antibiotic resistance against bacteria, fungi, and viruses by disrupting microbial membranes, generating ROS, and interfering with DNA and protein synthesis. Nanoscale size and large surface area make them critical for developing advanced antimicrobial treatments. They are effective antibacterial agents for treating infections, suitable in water purification systems, and fostering innovation by creating green, economically viable antibacterial materials. Therefore, green synthesis of metal and metal oxide nanoparticles for antibacterial agents supports several United Nations Sustainable Development Goals (SDGs), including health improvement, sustainability, and innovation.

Maryland adults’ perspectives on oral cancer prevention and early detection

Need for a national oral cancer biobank for cutting-edge translational research in developing countries.

BackgroundPublished studies assessing the association of human papillomavirus (HPV) and oral cancer, often include cases with additional confounders such as alcohol, tobacco, thus, precluding the assessment of HPV as a independent risk factor. Further apart from eliciting the mere presence of HPV, it is vital that the nature of the association is delineated for eliciting a causal inference. Thus, the present study assessed the presence and nature of the association of HPV in oral cancer cases with and without known risk factors.MethodsThe study compares the prevalence of HPV in oral cancer cases with known risk factors (group 1, n=15) to oral cancer (group 2, n=15) and oral epithelial dysplasia (group 3, n=15) cases with no known risk factors using PCR. Cases which are positive for HPV were subjected to p16 and p53 immunostaining to determine potential causal inference.ResultsHPV 16 was detected in only 1 case of group I, 3 cases of group II, and was absent in group III. HPV 18 was negative in all the 3 groups. All the HPV positive cases were negative for p16 and positive for p53 immunostaining.ConclusionsOnly a minor proportion of oral cancer cases without risk factors were positive for HPV 16. Even among these HPV 16 positive cases, the immunostaining profile (p53 positive and p16 negative) excludes the involvement of E6 and E7 mediated carcinogenesis. Thus even the weak HPV association noted in the present study cases may not be of causal nature.

Nanotechnology emerged as a scientific innovation in the 21st century. Metallic nanoparticles (metal or metal oxide nanoparticles) have attained remarkable popularity due to their interesting biological, physical, chemical, magnetic, and optical properties. Metal-based nanoparticles can be prepared by utilizing different biological, physical, and chemical methods. The biological method is preferred as it provides a green, simple, facile, ecofriendly, rapid, and cost-effective route for the green synthesis of nanoparticles. Plants have complex phytochemical constituents such as carbohydrates, amino acids, phenolics, flavonoids, terpenoids, and proteins, which can behave as reducing and stabilizing agents. However, the mechanism of green synthesis by using plants is still highly debatable. In this report, we summarized basic principles or mechanisms of green synthesis especially for metal or metal oxide (i.e., ZnO, Au, Ag, and TiO2, Fe, Fe2O3, Cu, CuO, Co) nanoparticles. Finally, we explored the medical applications of plant-based nanoparticles in terms of antibacterial, antifungal, and anticancer activity.

Background: Oral cancer exists as a major international health challenge. Circulating tumor DNA (ctDNA) represents a non-invasive biomarker through liquid biopsy because it enables cancer detection disease monitoring and therapy response assessment. This study aimed at Pathological Insights into Liquid Biopsy by evaluating the role of circulating tumor DNA in oral cancer Prognosis and Therapy. Methods: The research implemented an ethical-approved (CIIT-RBM/006/ISB) cross-sectional method from June to December 2024 to obtain 80 EDTA blood plasma samples from oral cancer patients mainly at Shaikh Zayed Hospital Lahore and PIMS Hospital Islamabad using consecutive sampling technique. firstly cell-free DNA was extracted followed by targeted sequencing to detect mutations that are specific to tumors. Using SPPS version 26. this study established a < 0.001 p-value as its statistical threshold using one-way ANOVA. Results: There were 52 males and 28 females in this study with average age of 56.4 ± 12.3 years. The majority of patients were male (65%), with a higher prevalence of late-stage tumors (Stage III-IV).. Significantly higher ctDNA levels (35.7 ± 5.4) were associated with tumor stage, lymph node involvement with poor survival outcome. The mean ctDNA yield was significantly higher in tumor tissues than in adjacent normal tissues (p < 0.001). Conclusion: The study demonstrated clinically significant evidence that ctDNA serves as a dependable biomarker for primary diagnosis which can be easily accessed through non-invasive methods in oral cancer cases. Ongoing large-scale studies should be followed to validate the discovered findings while developing consistent clinical procedures.

Lip and oral cavity cancers are among the top 10 cancer causes and mortality globally. Some countries in the Indian subcontinent bear a disproportionately higher burden of lip and oral cavity cancers. Detailed analysis of lip and oral cavity cancers in the Indian subcontinent using all available data is important for effective policy planning. This paper aims to summarise the total burden of lip and oral cavity cancer and compare it across countries within the Indian subcontinent. Data from the Global Cancer Observatory (GCO) and Global Burden of Disease (GBD) Study were extracted to analyse cancer incidence, prevalence, mortality and cancer risk before reaching 74 years. Furthermore, summary estimates of years of life lost (YLL), years lived with disability (YLDs) and disability-adjusted life years (DALYs) attributable to lip and oral cavity cancers were extracted from the GBD database. The data of individual countries within the Indian subcontinent were used for comparison. The estimated number of deaths from lip and oral cavity cancers for 2019 was 90732 in the Indian subcontinent. The Indian subcontinent accounted for 45.3% of the deaths attributable to lip and oral cavity cancers. The incidence of lip and oral cavity cancers in the Indian subcontinent ranged from 3.18 per 100,000 population in Maldives to 12.76 per 100,000 population in Pakistan. The incidence rate of lip and oral cavity cancer in India was 7.54 per 100,000 population. However, due to the population size, India accounted for 104837 incident cases of lip and oral cavity cancers annually. The estimated number of prevalent and incident cases of lip and oral cavity cancers from the Indian subcontinent in 2019 was 0.46 million (30% of overall cases globally) and 0.15 million (39% of incident cases globally), respectively. The Indian subcontinent also accounted for 50% of the DALYs attributable to lip and oral cavity cancers worldwide. The Indian subcontinent accounts for disproportionately higher cases and deaths due to lip and oral cavity cancers than other regions. It calls for urgent policy action to prevent the disease spread, early diagnosis and optimal management of lip and oral cavity cancers in the Indian subcontinent.

Human death from oral cancer is the 4th most common in male and over all 6th most common cause of cancer death in Taiwan. Surgery, radiotherapy in combination with chemotherapy is the most common line of treatment for oral cavity cancer. Although cisplain, 5FU, Docetexal, Pinyangmycin etc are the common drugs being used in clinic, there is no any specific drug for oral cavity cancer. In that direction BO-1090 a newly synthesized alkylating agent has potential to be more specific drug for oral cancer based on its potent in vitro cytotoxicty to oral cancer cells, such are OECM-1, SAS, OC3 and CAL-27 in comparison to other cancer cell lines, including lung cancer H1299, prostate cancer cell PC3 and neuronal cell line U87. BO-1090 target DNA for its cytotoxic effects that have been confirmed by alkaline gel shift assay, BrdU based DNA synthesis inhibition assay, Comet assay and γH2x detection. BO-1090 has been tested for its therapeutic potential in SAS cell xenograft mouse. At a dose of 60 mg/Kg i.v five times, it significantly delays the tumor growth in comparison to the control group of mice. Its tumor efficacy in SAS cell xenograft is better than the cisplatin at dose of 4 mg/kg i.v three times. Based on these preliminary results it suggests that B0-1090 can be a useful drug either alone or in combination with other knows drugs in oral cavity cancer therapy. As to the modes of actions of BO-1090, here is activation of CHK-2 check point in response to DNA damage by BO-1090 as well as late activation of p53 and p21. The late activation of P53 may be due to DNA replication blocked by BO1090. During propidium iodide staining based cell cycle analysis, BO-1090 induces G1/ S phase arrest in SAS cell that further confirmed by BrdU incorporation based pulse chase experiment. G1/S phase arrest may be due to combined effects of CDC 25A degradation and activation of p53 and p21 in response to BO-1090 induced DNA damage. G1/S phase arrest in cell by BO-1090 is not a common feature of a DNA alkylating agent, most of DNA alkylating agent induce G2/M phase arrest. In Annexin V based apoptosis assay, our results show that BO-1090 induces apoptosis in SAS and OECM-1 cell by time and dose dependent manner through caspase dependent pathway. By using bioinformatic approach and preliminary experiments suggest that PIM-1 may be also one of its molecular targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3512.