Solid CaCO3 Formation in Glioblastoma Multiforme and its Treatment with Ultra-Nanoparticulated NPt-Bionanocatalysts.

BACKGROUND: Glioblastoma multiforme (GBM), the most prevalent form of central nervous system (CNS) cancer, stands as a highly aggressive glioma deemed virtually incurable according to the World Health Organization (WHO) standards, with survival rates typically falling between 6 to 18 months. Despite concerted efforts, advancements in survival rates have been elusive. Recent cutting-edge research has unveiled bionanocatalysts with 1% Pt, demonstrating unparalleled selectivity in cleaving C-C, C-N, and C-O bonds within DNA in malignant cells. The application of these nanoparticles has yielded promising outcomes. OBJECTIVE: The objective of this study is to employ bionanocatalysts for the treatment of Glioblastoma Multiforme (GBM) in a patient, followed by the evaluation of obtained tissues through electronic microscopy. METHODS: Bionanocatalysts were synthesized using established protocols. These catalysts were then surgically implanted into the GBM tissue through stereotaxic procedures. Subsequently, tissue samples were extracted from the patient and meticulously examined using Scanning Electron Microscopy (SEM). RESULTS AND DISCUSSION: Detailed examination of biopsies via SEM unveiled a complex network of small capillaries branching from a central vessel, accompanied by a significant presence of solid carbonate formations. Remarkably, the patient subjected to this innovative approach exhibited a three-year extension in survival, highlighting the potential efficacy of bionanocatalysts in combating GBM and its metastases. CONCLUSION: Bionanocatalysts demonstrate promise as a viable treatment option for severe cases of GBM. Additionally, the identification of solid calcium carbonate formations may serve as a diagnostic marker not only for GBM but also for other CNS pathologies.

S-allyl-cysteine triggers cytotoxic events in rat glioblastoma RG2 and C6 cells and improves the effect of temozolomide through the regulation of oxidative responses.

Glioblastoma (GBM) is an aggressive form of cancer affecting the Central Nervous System (CNS) of thousands of people every year. Redox alterations have been shown to play a key role in the development and progression of these tumors as Reactive Oxygen Species (ROS) formation is involved in the modulation of several signaling pathways, transcription factors, and cytokine formation. The second-generation oral alkylating agent temozolomide (TMZ) is the first-line chemotherapeutic drug used to treat of GBM, though patients often develop primary and secondary resistance, reducing its efficacy. Antioxidants represent promising and potential coadjutant agents as they can reduce excessive ROS formation derived from chemo- and radiotherapy, while decreasing pharmacological resistance. S-allyl-cysteine (SAC) has been shown to inhibit the proliferation of several types of cancer cells, though its precise antiproliferative mechanisms remain poorly investigated. To date, SAC effects have been poorly explored in GBM cells. Here, we investigated the effects of SAC in vitro, either alone or in combination with TMZ, on several toxic and modulatory endpoints-including oxidative stress markers and transcriptional regulation-in two glioblastoma cell lines from rats, RG2 and C6, to elucidate some of the biochemical and cellular mechanisms underlying its antiproliferative properties. SAC (1-750 µM) decreased cell viability in both cell lines in a concentration-dependent manner, although C6 cells were more resistant to SAC at several of the tested concentrations. TMZ also produced a concentration-dependent effect, decreasing cell viability of both cell lines. In combination, SAC (1 µM or 100 µM) and TMZ (500 µM) enhanced the effects of each other. SAC also augmented the lipoperoxidative effect of TMZ and reduced cell antioxidant resistance in both cell lines by decreasing the TMZ-induced increase in the GSH/GSSG ratio. In RG2 and C6 cells, SAC per se had no effect on Nrf2/ARE binding activity, while in RG2 cells TMZ and the combination of SAC + TMZ decreased this activity. Our results demonstrate that SAC, alone or in combination with TMZ, exerts antitumor effects mediated by regulatory mechanisms of redox activity responses. SAC is also a safe drug for testing in other models as it produces non-toxic effects in primary astrocytes. Combined, these effects suggest that SAC affords antioxidant properties and potential antitumor efficacy against GBM.

Catalytic Nanomedicine as a Therapeutic Approach to Brain Tumors: Main Hypotheses for Mechanisms of Action.

Glioblastoma multiforme (GBM) is the most aggressive primary malignant tumor of the brain. Although there are currently a wide variety of therapeutic approaches focused on tumor elimination, such as radiotherapy, chemotherapy, and tumor field therapy, among others, the main approach involves surgery to remove the GBM. However, since tumor growth occurs in normal brain tissue, complete removal is impossible, and patients end up requiring additional treatments after surgery. In this line, Catalytic Nanomedicine has achieved important advances in developing bionanocatalysts, brain-tissue-biocompatible catalytic nanostructures capable of destabilizing the genetic material of malignant cells, causing their apoptosis. Previous work has demonstrated the efficacy of bionanocatalysts and their selectivity for cancer cells without affecting surrounding healthy tissue cells. The present review provides a detailed description of these nanoparticles and their potential mechanisms of action as antineoplastic agents, covering the most recent research and hypotheses from their incorporation into the tumor bed, internalization via endocytosis, specific chemotaxis by mitochondrial and nuclear genetic material, and activation of programmed cell death. In addition, a case report of a patient with GBM treated with the bionanocatalysts following tumor removal surgery is described. Finally, the gaps in knowledge that must be bridged before the clinical translation of these compounds with such a promising future are detailed.

Effect of catalytic nanomedicine on amputation-stage chronic venous ulcers: four case studies.

BACKGROUND: Chronic ulcers represent a significant challenge for patients with compromised microcirculation. As a novel branch of research, catalytic nanomedicine has exhibited promising outcomes with the development of nanostructured composites designed to disinfect and improve the healing of chronic wounds through the incorporation of bionanocatalysts within gel matrices. PURPOSE: This study aimed to assess the impact of bionanocatalysts on 4 patients suffering from chronic venous ulcers, which had previously been indicated for lower extremity amputation. METHODS: Bionanocatalysts were synthesized and incorporated into a gel matrix. Monthly debridement was conducted with the objective of completely removing nonviable tissue. The bionanocatalyst-embedded gel was applied every other day, covering the entire wound surface and secured with a secondary dressing. RESULTS: Encouragingly, all cases exhibited complete wound closure, and patients reported no adverse side effects. CONCLUSION: These findings offer robust support for the utilization of this technology in wound healing and prompt a reevaluation of the hypothesis regarding the mechanism of action of bionanocatalysts in chronic wounds. Future research endeavors should aim to quantitatively assess the bionanocatalysts' influence on the trajectory of wound healing, as well as address the myriad challenges associated with managing chronic wounds.

Catalytic nanomedicine: a brief review of bionanocatalysts.

Catalytic nanomedicine is a research area and source of disruptive technology that studies the application of bionanocatalysts (organically functionalized mesoporous nanostructured materials with catalytic properties) in diverse areas such as disinfection, tissue regeneration in chronic wounds and oncology. This paper reviews the emergence of catalytic nanomedicine in 2006, its basic principles, main achievements and future perspectives, as well as giving a summary of the knowledge gaps that need to be addressed to exploit the full potential of this novel discipline. This review intends to foster knowledge dissemination regarding catalytic nanomedicine, and to encourage further research to elucidate the mechanisms and possible applications of these nanomaterials.

Catalytic Nanomedicine - A new Approach and Solution for Chronic Ulcers: Case Series.

Chronic ulcers are a major public health problem, due to their chronic nature, their poor response to treatment, the high frequency of recurrences, and their affection to the patient's quality of life. Even with the development of new therapies in the field of chronic wound care, chronic ulcers remain a clinical problem. As a novel branch of research, Catalytic Nanomedicine has offered promising results in disinfection and treatment of chronic wounds through the use of bionanocatalysts, organically functionalized mesoporous nanostructured materials with catalytic properties. Particularly, Cu/TiO2-SiO2 mixed oxide bionanocatalysts have shown favorable results for chronic ulcer healing. In this work, we present the treatment of 15 patients (8 females and 7 males, mean age of 69.59 ± 12.07 years old) affected with chronic ulcers (wound age ranging from 4 months to 10 years old, mean size of 12.94 ± 18.20 cm2) by the administration of Cu/TiO2-SiO2 bionanocatalysts embedded in a nanoemulsion matrix. In all cases, complete epithelialization and healing of the lesions was achieved (healing time from 3 to 35 weeks), without the appearance of side effects. Wound healing time was analyzed in the context of initial wound size, wound's age, patient's age, and concomitant conditions, being wound size and patient's age the main factor affecting the duration of the treatment with the bionanocatalysts.

Spectroscopic Analysis and Microbicidal Effect of Ag/TiO2-SiO2 Bionanocatalysts.

Silver, especially nanostructured silver, has been found to exhibit antimicrobial properties by disrupting the function of bacterial cell walls. Nonetheless, strains of bacteria have been reported to resist silver nanoparticles. The highly efficient mutational mechanisms of bacteria, capable of overcoming modern antimicrobial compounds, make it critical to develop new materials that target genetic material, regardless of nucleotide sequence or protein structure, without being toxic to the patient. This work evaluates the microbicidal properties of a catalytic, nanostructured, organically functionalized, titanosilicate matrix (bionanocatalysts) impregnated with silver. The bionanocatalysts were synthesized by the sol-gel method using silver acetate as the silver precursor. The effect of the bionanocatalysts against clinically important strains of bacteria and yeasts was evaluated. In addition, the physicochemical composition and in vitro reactivity on DNA were studied. The antibiogram analysis revealed that the compound could inhibit the growth (inhibition halos of up to 15 ± 0.9 mm) of all the strains studied (bacteria and yeasts) at low concentrations of silver, thus reducing the toxicity associated with platinum. In this work, by adding silver in the catalytic TiO2-SiO2 matrix, the intrinsic microbicidal properties of the metal were enhanced: the results provided a valuable compound exhibiting reduced toxicity and antimicrobial effects that could potentially be used as a potent disinfectant against drug-resistant strains, as found in hospitals, for instance.

IC50 Evaluation of Platinum Nanocatalysts for Cancer Treatment in Fibroblast, HeLa, and DU-145 Cell Lines.

Cancer is a major public health problem being one of the main causes of morbidity and mortality today. Recent advances in catalytic nanomedicine have offered new cancer therapies based on the administration of nanoparticles (NPs) of platinum (Pt) dispersed in catalytic mesoporous nanomaterials (titania, TiO2) with highly selective cytotoxic properties and no adverse effects. A half maximal inhibitory concentration (IC50) study was carried out in cancerous cell lines (HeLa, DU-145, and fibroblasts) to evaluate the cytotoxic effect of different nanomaterials [Pt/TiO2, TiO2, and Pt(acac)2] synthesized by the sol-gel method at concentrations 0-1000 µg/mL. The assays showed that IC50 values for Pt in functionalized TiO2 (NPt) in HeLa (53.74 ± 2.95 µg/mL) and DU-145 (75.07 ± 5.48 µg/mL) were lower than those of pure TiO2 (74.29 ± 8.95 and 82.02 ± 6.03 µg/mL, respectively). Pt(acac)2 exhibited no cytotoxicity. Normal cells (fibroblasts) treated with NPt exhibited no significant growth inhibition, suggesting the high selectivity of the compound for cancerous cells only. TiO2 and NPt were identified as antineoplastic compounds in vitro. Pt(acac)2 is not recommendable because of the low cytotoxicity observed.

Physicochemical properties and in vivo evaluation of Pt/TiO2-SiO2 nanopowders.

AIM: Sol-gel is a suitable and advantageous method to synthesize mixed oxide nanomaterials with unique physicochemical and biological properties. MATERIALS & METHODS: In this work, TiO2-SiO2 nanopowders cogeled with platinum acetylacetonate were developed and studied in the perspective of nanomedicine. The physicochemical properties of the Pt/TiO2-SiO2 nanopowders, named NanoRa2-Pt, were evaluated in detail by means of complementary spectroscopic and microscopic tools. The nanopowder's biocatalytic efficiency in wound healing was evaluated in a Type I diabetes animal model. RESULTS: These are TiO2-SiO2 submicron mesoporous particles with variable size and shape containing ultra-small platinum nanoparticles with catalytic properties. CONCLUSION: The use of NanoRa2-Pt catalyzes the natural healing processes with a faster remodeling stage. These sols, which we call nanobiocatalysts, belong to an emerging and very promising research field known as catalytic nanomedicine.

Uso de la nanopartícula de SiO 2 -TiO 2 en el tratamiento de úlceras en pie diabético: comunicación preliminar / Using SiO 2 - TiO 2 nanoparticle in the treatment of diabetic foot ulcers: preliminary communication

Resumen Una de las complicaciones más graves de la diabetes mellitus es el pie diabético, que resulta de la suma de factores como: macroangiopatía, microangiopatía y neuropatía que disminuyen el flujo vascular y causan pequeñas lesiones que rápidamente progresan a úlceras y pueden abarcar todos los tejidos; la clasificación de Wagner1 señala cómo se puede progresar de una pequeña lesión superficial a una profunda, y que se extienda a los tejidos profundos: tendones, músculos y aún hueso, y dañar gravemente la salud, con inminencia de muerte por sepsis. El tratamiento convencional tiene buenos resultados en general, pero requiere un cuidadoso programa de atención local, protección de mayores lesiones, antibióticos, etc., y si no hay resultado, puede terminar en amputación. La utilización de nanopartículas de óxidos metálicos, que consisten de dióxido de silicio (SiO2) y dióxido de tinanio (TiO2), preparadas mediante la técnica sol-gel, pueden ofrecer una alternativa viable en el tratamiento de la úlcera diabética, debido a un mecanismo que permite mantenerla seca y, al mismo tiempo, inhibe el crecimiento de bacterias mediante un efecto bíocatalítico2. Para evaluar el uso de estas nanopartículas en el pie diabético, se realizó un protocolo de investigación en un grupo de pacientes que acuden al Centro Especializado en la Atención del Paciente Diabético "Dr. Manuel González Rivera", dependiente de la Secretaría de Salud del Distrito Federal; este protocolo fue aprobado por la Dirección de Enseñanza e Investigación de la propia Secretaría, con el número de registro 101/100/014/13. Se estudió a 62 pacientes con diversas formas de úlcera diabética y se aplicaron las nanopartículas haciendo una curación cada 48 horas, fueron evaluadas con fotografías seriadas y cultivos de la úlcera. Todos los pacientes que recibieron el tratamiento lograron la curación, con desaparición de las úlceras y cicatrización satisfactoria. Conclusión: La aplicación tópica de las nanopartículas de SiO2 y TiO2 parece ser de utilidad en el tratamiento de la úlcera diabética.

Abstract One of the most severe complications of diabetes mellitus is the diabetic foot, which is the sum of macroangiopathy, microangiopathy and neuropathy, which leads to low vascular flow, and development of lesions which rapidly progress to ulcer and may attain all tissues; the Wagner classification1 shows how a little superficial lesion may affect all tissues: tendons, muscles and even bones, to severely affect the general health and may end on death by sepsis. The conventional treatment has good results, but requires a careful program of local attention, protection from larger lesions, antibiotics, etc., and if does not have good results, may ends on foot amputation. The use of nanoparticles of metallic oxides, silicium dioxide and titanium dioxide, prepared by the sol-gel technique, may offer a viable alternative for diabetic ulcer treatment due a mechanism which allows to keep it dry and at the same time, inhibit bacterial growing through a biocatalytic effect2. To evaluate the use of these nanoparticles in diabetic foot, a research protocol was established in a group of diabetic patients who attend to the Center Specialized on Handling of the Diabetic Patient from Mexico City of Secretary of Health; this protocol was approved by the Educations and Research Direction of the Secretary of Health. 62 diabetic patient with diabetic ulcers of different degree were studied; the nanoparticles were applied every 48 hours and evaluated with photos and bacterial cultures. All patients who received the complete treatment healed their ulcers, with satisfactory healing. Conclusion: The topical application of metallic oxides nanoparticles seems to be useful in the treatment of diabetic ulcers.