Phototherapy with gold nanoparticles for the reduction of brain tumors

Background Gliomas are the most common intracranial primary tumors, accounting for more than 30% of central nervous system neoplasms. Grades I and II are considered low-grade (low-risk) gliomas, while grades III and IV are considered high-grade (high-risk) gliomas [1]. Current therapy includes surgery, high-dose postoperative radiation, and chemotherapy. . However, advances in conventional glioma therapy are unable to provide adequate medication for glioma [2]. The blood-brain barrier (BBB) and tumor blood-brain barrier (BBTB) prevent drug delivery systems and nanodrugs from entering into brain. However, ligand-mediated nanodrug delivery systems have greatly improved the therapeutic treatment of glioma [3]. In 2015, transferrin peptide (Tfpep)-targeted gold nanoparticles (Tfpep-Au NPs) loaded with the photodynamic prodrug Pc 4 were designed and compared with gold nanoparticles administered with this prodrug. As a result, in vitro studies of human glioma cancer lines showed increased cellular uptake of targeted compared to untargeted nanoparticles [4]. In 2019, when glioblastoma cells that overexpress the endosomal Na+/H+ exchanger (NHE9) are exposed to gold nanoparticles, they accumulate high amounts of gold. In this way, irradiation of these resulting cells with near infrared light caused the death of tumor cells [5]. In a record from 2021, gold nanoparticles conjugated with milk protein were developed, to this nanoparticle glutathione and polyethylene glycol were introduced. This conjugate was administered orally and 11-fold higher concentrations of gold nanoparticles were measured in the bloodstream. And, by having contact with laser irradiation, the size of the tumor was reduced [6]. In the current year 2022, the enhancing effect of hollow shells of gold and iron oxide nanoparticles (hybridosomes) in radiotherapy for gliobastoma was evaluated. The oxide was found to have no beneficial effect for radiotherapy, however, gold nanoparticles increased the median survival of mice by nearly 20% compared to radiotherapy alone and mice without any treatment . In addition, in the follow-up of the tumor after treatment, the existence of this decrease was revealed by magnetic resonance imaging and bioluminescence, due to the permanence of the nanoparticles in the tumor site [7]. Despite the obstacles regarding the permeability of the blood-brain barrier in the treatment of gliomas, one of the goals of nanomedicine remains to develop chemically modified drug derivatives or chemically modified nanoparticulate drug vectors capable of crossing biological barriers, in particular the BBB [8]. Research Question Which phototherapy system, based on gold nanoparticles, has achieved the greatest reduction in tumor size in preclinical models? Inclusion criteria Registries that use gold nanoparticles for the treatment of gliomas. Records describing the phototherapy system used. Clinical registries that carry out in vivo studies with animals. Records that talk about any type of glioma. Records describing the method of quantification of gold nanoparticles. Exclusion criteria Records that are systematic reviews and studies of the state of the art. Full access records provided by the databases of the Autonomous University of Ciudad Juárez. Records that do not describe the process for obtaining gold nanoparticles. Records published before 2018. Records in languages other than English. Overall objective Determine the type of phototherapy that has the best efficacy in reducing brain tumors. Specific objectives To identify the characteristics and properties of gold nanoparticles responsible for the transport of drugs for the treatment of glioma. To recognize the advantages and disadvantages of the different nanocarriers used for tumor reduction. To compare the functionality of the types of phototherapy that use nanoparticles for the treatment of brain tumors. The treatment of gliomas using traditional techniques has been functional in increasing people's life expectancy, however, these methods are very invasive, and, due to the permeability of the blood-brain barrier, it is necessary to look for other options that allow drugs have better access to the glioma. Due to this need and the discovery of nanoparticles, treatments using these nanoparticles have been developed to ensure a safer and more efficient effect in drug transport. This provides a new and better outlook for both patients and health personnel, since, being a direct method, the tumor would be attacked directly without compromising healthy cells. Despite being a novel technique that could bring with it endless benefits, there are still questions about its effectiveness and operation in humans. For this reason, it is intended to carry out a systematic review of the different nanoparticles that have the ability to cross the blood-brain barrier and that ensure the effective transport of drugs for the treatment of glioma, as well as the characteristics that the transport of these nanoparticles implies. Proposed methodology The selected methodology will be the following: Choice of databases: ScienceDirect, PubMed, ClinicalTrials and EBSCOHOST. Definition of search strategies, indicating terms and Boolean operators. Proposed: ("blood brain barrier" OR BBB) AND ("Gold nanoparticles" OR AuNP) AND (glioma OR "brain tumor") AND (phototherapy) Choice of studies and articles that meet the inclusion and exclusion criteria. Realization of PRISMA diagram for accounting and screening of records included in the systematic review. Evaluation of the studies included in the review. Analysis of the selected studies that provide the necessary information about phototherapy techniques that use gold nanoparticles that cross the blood-brain barrier for the treatment of gliomas. Extraction of results of the selected studies for the comparison of nanoparticles. Interpretation of the results obtained for the fulfillment of each one of the objectives. Conclusion with the most effective phototherapy option for the reduction of brain tumors