Classic Recurrent Ependymoma in Posterior Cranial Fossa Treated with Coated-Bionanocatalysts: Case Report

Case Report

Austin J Nanomed Nanotechnol. 2024; 12(1): 1074.

Classic Recurrent Ependymoma in Posterior Cranial Fossa Treated with Coated-Bionanocatalysts: Case Report

Tessy Lopez-Goerne1,2*; Francisco J Padilla-Godínez1,3; Daniel Álvarez1; Antonela GonzÁlez-Bondani1; Rafael Valiente1; Fernando Chico-Ponce de Leónl4; Vicente GonzÁlez-Carranza4; Pilar Dies-SuÁrez5; José Omar Navarro-FernÁndez5; Abel Santamaria1

1Autonomous Metropolitan University – Xochimilco, Department of Health Care, Mexico

2Tulane University, Department of Chemical and Biomolecular Engineering, United States

3Western Institute of Technology and Higher Education, Department of Mathematics and Physics, Mexico

4Children’s Hospital of Mexico “Federico Gomez”, Department of Neurosurgery, Mexico City 06720, Mexico

5National Institute of Cancerology, Department of Head and Neck, Mexico

*Corresponding author: Tessy López-Goerne, Laboratory of Nanotechnology and Nanomedicine, Department of Health Care, Autonomous Metropolitan University-Xochimilco, Mexico City 04960, Mexico. Email: tessy3@prodigy.net.mx

Received: September 11, 2024 Accepted: September 30, 2024 Published: October 07, 2024

Abstract

Ependymomas are genetically varied glial tumors that form in the Central Nervous System (CNS). They originate from cells in the ventricular system and can develop intracranially as well as in the spinal cord. Primary treatments, especially for intracranial ependymomas in children, frequently fail to prevent recurrence, which can happen within two years or even several years post-diagnosis. Among novel treatments, bionanocatalysts are nanostructured materials made up of oxide matrices that possess catalytic properties and biochemical characteristics. Certain bionanocatalysts can selectively induce cytotoxic effects in cancer cells while remaining harmless to healthy cells. In this regard, in this study, we present the case of a pediatric patient with classic recurrent ependymoma in the posterior cranial fossa who was previously receiving only palliative care. The patient had already received several neurosurgeries focused on the extraction of tumor tissue, which had resulted in several side effects and a significant reduction in the quality of life the patient. Due to the ineffectiveness of previous treatments, we decided to implement a protocol using oncologic bionanocatalysts for treatment. After 5 years, the patient is in remission with no significant or evident side effects. This research highlights the selective cytotoxic activity of these nanostructures on cancer cells, sparing healthy cells in surrounding tissues, unlike other chemotherapeutics such as cisplatin.

Keywords: Recurrent Ependymoma; bionanocatalyst; NPt; Posterior Cranial Fossa; Catalysis

Introduction

Ependymomas are genetically diverse glial tumors that develop in the Central Nervous System (CNS), originating from cells of the ventricular system and growing both intracranially and in the spinal cord [1,2]. These tumors affect both children and adults, accounting for approximately 5-16% of all CNS tumors, with over 3,000 deaths in the US alone over the past 16 years [3–5]. The standard treatment involves surgical resection followed by radiotherapy. Gross Total Resection (GTR) significantly improves patient survival, while adjunct radiotherapy aims to reduce recurrence [5,6]. Although chemotherapy is controversial, some pediatric patients have benefited from its use [5,7,8]. However, side effects, including severe cognitive impairments, have been noted, particularly in children [9]. Consequently, exploring novel therapeutic approaches is crucial for improving the quality of life of these patients.

Traditional diagnosis of ependymomas relies on histopathological characteristics, using WHO histologic grading and morphological patterns [10]. This classification is limited by the heterogeneous nature of tumor progression and observer variability. Significant improvements in diagnosis have been made through DNA methylation analysis, which identifies nine to ten different types of ependymomas based on genetic aberrations [5,11,12]. This advancement led the 2021 WHO Classification of Tumours of the Central Nervous System to differentiate between multiple molecularly defined types [13]. Despite these advances, treatment strategies for ependymomas continue to evolve. Posterior fossa ependymomas, which develop in the fourth ventricle or cerebellopontine angle, are associated with complex genetic changes, such as alterations in DNA methylation and overexpression of specific proteins [14]. DNA methylation analysis and sequencing have identified subtypes like PFA and PFB, recognized in the 2021 WHO classification [13]. PFB ependymomas generally have a better prognosis. Immunostaining for histone H3 p.K27 trimethylation is a crucial marker for differentiating between PFA and PFB subgroups, often used as a surrogate for DNA methylation profiling [15]. Childhood ependymomas frequently occur in the back of the skull, with prognosis influenced by tumor location [16]. MRI may reveal well-defined tumors, sometimes with hemorrhage and calcifications, located within the fourth ventricle or extending laterally through natural foramina [17].

Complete surgical resection is critical for prognosis, though it is more challenging for tumors in the floor or lateral wall of the fourth ventricle, often leading to worse outcomes due to potential neurological deficits [18]. Primary therapies, particularly for intracranial ependymomas in children, often do not prevent recurrence, which can occur within two years or many years after diagnosis [16]. There is no clear consensus on the optimal treatment strategy, and apart from CAR-T cell therapy, few recent novel treatments have been developed [19]. Recurrences, especially in specific molecular subgroups, typically occur locally but can spread throughout the CNS [20]. Treatment options at this stage include surgery and radiotherapy, though re-irradiation may cause cognitive impairment: the decision to use focal or craniospinal radiation therapy depends on the patient's age and the risk of metastatic disease [21].

Bionanocatalysts are nanostructured materials composed of oxide matrices with catalytic properties and biochemical characteristics [22–24]. These materials are significant for biomedical research and clinical purposes due to their biocompatibility and selectivity for various targets. Some bionanocatalysts can selectively induce cytotoxic effects in cancer cells while being innocuous to healthy cells. The cytotoxic effects of bionanocatalysts are due to their ability to disrupt organic bonds, such as carbon-carbon and carbon-nitrogen bonds, leading to alterations in macromolecules like nucleic acids [25]. Bionanocatalysts form complexes with nucleotide chains, causing molecular degradation through combustion and dephosphorylation reactions, ultimately inhibiting replication. These catalysts also possess additional components, enhancing their biocompatibility and specificity for cancer cells, making them promising candidates for antitumor therapies. Titanium dioxide (titania)-based bionanocatalysts are noted for their thermal stability, crystalline structure, biocompatibility, and surface area [26]. Their catalytic properties have been studied for various antitumor applications [27].

This work describes a case of a recurrent ependymoma tumor in the posterior fossa of a six-year-old child initially diagnosed with frontal ependymoma and already in palliative care. The patient underwent two resection surgeries, with a third surgery following relapse, incorporating treatment with platinum-coated bionanocatalysts (1%), renamed as NPt-Ped. These nanoparticles were applied to all tumor zones during surgery. Post-treatment follow-up with Magnetic Resonance Imaging (MRI) has shown general tumor reduction since 2017.

Materials and Methods

NPt-Ped Surface-Coated Bionanocatalysts Synthesis

NPt-Ped is a type of coated bionanocatalyst with ultra-nanostructured anatase crystallinity, synthesized using previously established methods [28]. The synthesis parameters have been optimized to achieve a particle size of less than 5 nm: this preparation method is foundational for developing oncogenic platinum-coated bionanocatalysts. Platinating agents are widely used in the treatment of various cancers, as many chemical carcinogens are DNA-reactive. Alkylation is a proposed mechanism for the interaction between cancer cells and chemotherapeutic agents. Characteristics such as acid sites, nanosized particles, and platinum in different oxidation states enable platinum-based drugs to effectively interact with cancer cells [29]. Surface coating of NPt-Ped with = 5 nm metallic particles is essential to induce additive toxicity in malignant cells and enhance biocompatibility with healthy cells [24].

Physicochemical Characterization of NPt-Ped

The particle size, grain size, morphology, and texture were examined using Transmission Electron Microscopy (TEM; JEM-2100F, JEOL, USA) operating at 200 kV. Samples were placed on copper grids coated with holey carbon films. The vibrational states and bond types were identified using Fourier-Transform Infrared Spectroscopy (FTIR). FTIR spectra were recorded at room temperature on a 40% sample–KBr transparent pellet with a Shimadzu IRAffinity-1 spectrometer, covering the 4000–400 cm-¹ range. Non-polarized Raman spectra of the powdered NPt-Ped samples were obtained in a near-backscattering geometry using a Horiba-Jobin Yvon LabRam micro-spectrometer (300 mm focal length spectrograph) equipped with an integrated Olympus BX40 microscope. Raman spectroscopy, a light scattering technique, involves scattering incident light from a high-intensity laser [30]. In this vibrational spectroscopy method, a small fraction of light (typically 0.0000001%) is scattered at different wavelengths, depending on the sample's chemical structure; this phenomenon is known as Raman scattering.

Clinical Case Story

A two-year-old male patient was admitted to the Department of Neurosurgery at the "Federico Gómez" Children's Hospital of Mexico in October 2012. His parents reported that he had experienced frequent vomiting, sleeplessness, irritability, and an increased head size over the past month. An MRI revealed a mass at the infratentorial level on the left side (Figure 1a-c). In December 2012, he underwent surgery, where a partial resection of the tumor was performed (Figure 1d-e). An intraoperative pathology study diagnosed the mass as a classic Ependymoma (Figure 1g). The patient began chemotherapy with Cisplatin, Vincristine, and adjuvant Etoposide.