Gold nanoparticle phototherapy for brain tumor shrinkage

Gliomas are the most common primary intracranial 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 cannot provide adequate medication for glioma [2]. The blood-brain barrier (BBB) and tumor blood-brain barrier (BBTB) prevent drug and nanodrug delivery systems from entering the 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 delivered with this prodrug. As a result, in vitro studies of human glioma cancer lines showed increased cellular uptake in targeted nanoparticles compared to non-targeted ones [4]. In 2019, when gliobastoma cells overexpressing the endosomal Na+/H+ exchanger (NHE9) are exposed to gold nanoparticles, they accumulate high amounts of gold. Thus, irradiation of these resulting cells with near-infrared light resulted in tumor cell death [5]. In 2021, gold nanoparticles conjugated with milk protein were developed, to which glutathione and polyethylene glycol were introduced. This conjugate was administered orally and 11 times higher concentrations of gold nanoparticles were measured in the bloodstream. And, upon contact with laser irradiation, tumor size was reduced [6]. In 2022, the potentiating effect of hollow shells of gold nanoparticles and iron oxide (hybridosomes) in radiotherapy for gliobastoma was evaluated. It was observed that oxide did not present any beneficial effect for radiotherapy, however, gold nanoparticles increased the median survival of mice by almost 20% compared to using radiotherapy alone and mice without any treatment. Moreover, in the follow-up of the tumor after treatment, the existence of this decrease was revealed by MRI and bioluminescence, this due to the permanence of the nanoparticles at the tumor site [7]. Despite the obstacles with respect to blood-brain barrier permeability in the treatment of gliomas, one of the goals of nanomedicine remains to develop chemically modified drug derivatives or nanoparticulate vectors of chemically modified drugs capable of crossing biological barriers, in particular the BBB [8]