RESUMEN
Head and neck squamous cell carcinomas are characterized by a high incidence of recurrence, especially in patients with locally advanced disease. Standard treatment strategies can be associated with severe side effects to healthy tissues that can negatively impact the patient's quality of life. Hyperthermia (HT) is a noninvasive treatment modality that has improved the effectiveness of chemotherapy (CT) and/or radiotherapy (RT) for the management of some solid neoplasms. In this context, the association of this approach with rationally designed nanomaterials may further enhance the treatment outcome. In this study, we demonstrate the enhanced effect of neoadjuvant HT in combination with hybrid nanoarchitectures enclosing a cisplatin prodrug (NAs-CisPt) and RT. All the treatments and their combinations have been fully evaluated by employing standardized chorioallantoic membrane tumor models of HPV-negative head and neck carcinoma. An improved tumor-shrinking effect was observed by the administration of the trimodal treatment (HT/NAs-CisPt/RT), which also highlighted a significant increase in apoptosis. Our findings demonstrate that the combination of HT with nanotechnology-based CT and RT in a certain order enhances the in vivo treatment outcome. On a broader basis, this study paves the way for the next exploration of noninvasive treatment approaches for the clinical management of oral cancer based on innovative strategies.
Asunto(s)
Quimioradioterapia , Neoplasias de Cabeza y Cuello , Hipertermia Inducida , Nanoestructuras , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/patología , Humanos , Hipertermia Inducida/métodos , Animales , Quimioradioterapia/métodos , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Terapia Neoadyuvante/métodos , Cisplatino/uso terapéutico , Línea Celular Tumoral , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Profármacos/química , Profármacos/farmacología , Profármacos/uso terapéuticoRESUMEN
Cisplatin chemoradiotherapy (CRT) is the established standard of care for managing locally advanced human papillomavirus-positive head/neck carcinoma. The typically young patients may suffer serious and long-time side effects caused by the treatment, such as dysphagia, and hearing loss. Thus, ensuring a satisfactory post-treatment quality of life is paramount. One potential replacing approach to the classical CRT involves the combination of standard-dose radiotherapy and radiosensitizers such as noble metal nanoparticles (NPs). However, several concerns about size, shape, and biocompatibility limit the translation of metal nanomaterials to the clinical practice. Here, it is demonstrated that a new model of nonpersistent gold nanoarchitectures containing cisplatin (NAs-Cluster-CisPt) generates, in combination with radiotherapy, a significant in vivo tumor-reducing effect compared to the standard CRT, achieving a complete tumor clearance in 25% of the immunocompetent models that persist for 60 days. These findings, together with the negligible amount of metals recognized in the excretory organs, highlight that the concurrent administration of NAs-Cluster-CisPt and radiotherapy has the potential to overcome some clinical limitations associated to NP-based approaches while enhancing the treatment outcome with respect to standard CRT. Overall, despite further mechanistic investigations being essential, these data support the exploiting of nonpersistent metal-nanomaterial-mediated approaches for oral cancer management.
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Quimioradioterapia , Cisplatino , Oro , Neoplasias de Cabeza y Cuello , Quimioradioterapia/métodos , Animales , Neoplasias de Cabeza y Cuello/terapia , Ratones , Humanos , Cisplatino/química , Cisplatino/uso terapéutico , Oro/química , Línea Celular Tumoral , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Infecciones por Papillomavirus/terapia , Nanoestructuras/química , Inmunocompetencia , PapillomaviridaeRESUMEN
Oral malignancies continue to have severe morbidity with less than 50% long-term survival despite the advancement in the available therapies. There is a persisting demand for new approaches to establish more efficient strategies for their treatment. In this regard, the human topoisomerase II (topoII) enzyme is a validated chemotherapeutics target, as topoII regulates vital cellular processes such as DNA replication, transcription, recombination, and chromosome segregation in cells. TopoII inhibitors are currently used to treat some neoplasms such as breast and small cells lung carcinomas. Additionally, topoII inhibitors are under investigation for the treatment of other cancer types, including oral cancer. Here, we report the therapeutic effect of a tetrahydroquinazoline derivative (named ARN21934) that preferentially inhibits the alpha isoform of human topoII. The treatment efficacy of ARN21934 has been evaluated in 2D cell cultures, 3D in vitro systems, and in chick chorioallantoic membrane cancer models. Overall, this work paves the way for further preclinical developments of ARN21934 and possibly other topoII alpha inhibitors of this promising chemical class as a new chemotherapeutic approach for the treatment of oral neoplasms.
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ADN-Topoisomerasas de Tipo II , Carcinoma de Células Escamosas de Cabeza y Cuello , Inhibidores de Topoisomerasa II , Humanos , ADN-Topoisomerasas de Tipo II/metabolismo , Inhibidores de Topoisomerasa II/farmacología , Inhibidores de Topoisomerasa II/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Línea Celular Tumoral , Animales , Quinazolinas/farmacología , Quinazolinas/uso terapéutico , Proliferación Celular/efectos de los fármacos , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Embrión de PolloRESUMEN
Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is characterized by high rate of recurrence, resulting in a poor survival. Standard treatments are associated with significant toxicities that impact the patient's quality of life, highlighting the urgent need for novel therapies to improve patient outcomes. On this regard, noble metal nanoparticles (NPs) are emerging as promising agents as both drug carriers and radiosensitizers. On the other hand, co-treatments based on NPs are still at the preclinical stage because of the associated metal-persistence.In this bioconvergence study, we introduce a novel strategy to exploit tumour chorioallantoic membrane models (CAMs) in radio-investigations within clinical equipment and evaluate the performance of non-persistent nanoarchitectures (NAs) in combination with radiotherapy with respect to the standard concurrent chemoradiotherapy for the treatment of HPV-negative HNSCCs. A comparable effect has been observed between the tested approaches, suggesting NAs as a potential platinum-free agent in concurrent chemoradiotherapy for HNSCCs. On a broader basis, our bioconvergence approach provides an advance for the translation of Pt-free radiosensitizer to the clinical practice, positively shifting the therapeutic vs. side effects equilibrium for the management of HNSCCs.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Infecciones por Papillomavirus , Fármacos Sensibilizantes a Radiaciones , Humanos , Carcinoma de Células Escamosas/patología , Platino (Metal)/farmacología , Platino (Metal)/uso terapéutico , Calidad de Vida , Infecciones por Papillomavirus/terapia , Cisplatino/uso terapéutico , Neoplasias de Cabeza y Cuello/inducido químicamente , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/inducido químicamente , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Fármacos Sensibilizantes a Radiaciones/farmacología , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodosRESUMEN
Pancreatic ductal adenocarcinoma (PDA) cells reprogram both mitochondrial and lysosomal functions to support growth. At the same time, this causes significant dishomeostasis of free radicals. While this is compensated by the upregulation of detoxification mechanisms, it also represents a potential vulnerability. Here we demonstrate that PDA cells are sensitive to the inhibition of the mevalonate pathway (MVP), which supports the biosynthesis of critical antioxidant intermediates and protect from ferroptosis. We attacked the susceptibility of PDA cells to ferroptotic death with selenorganic compounds, including dibenzyl diselenide (DBDS) that exhibits potent pro-oxidant properties and inhibits tumor growth in vitro and in vivo. DBDS treatment induces the mobilization of iron from mitochondria enabling uncontrolled lipid peroxidation. Finally, we showed that DBDS and statins act synergistically to promote ferroptosis and provide evidence that combined treatment is a viable strategy to combat PDA.
Asunto(s)
Ferroptosis , Neoplasias Pancreáticas , Selenio , Humanos , Páncreas , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Peroxidación de Lípido , Neoplasias PancreáticasRESUMEN
The key properties and high versatility of metal nanoparticles have shed new perspectives on cancer therapy, with copper nanoparticles gaining great interest because of the ability to couple the intrinsic properties of metal nanoparticles with the biological activities of copper ions in cancer cells. Copper, indeed, is a cofactor involved in different metabolic pathways of many physiological and pathological processes. Literature data report on the use of copper in preclinical protocols for cancer treatment based on chemo-, photothermal-, or copper chelating-therapies. Copper nanoparticles exhibit anticancer activity via multiple routes, mainly involving the targeting of mitochondria, the modulation of oxidative stress, the induction of apoptosis and autophagy, and the modulation of immune response. Moreover, compared to other metal nanoparticles (e.g. gold, silver, palladium, and platinum), copper nanoparticles are rapidly cleared from organs with low systemic toxicity and benefit from the copper's low cost and wide availability. Within this review, we aim to explore the impact of copper in cancer research, focusing on glioma, the most common primary brain tumour. Glioma accounts for about 80% of all malignant brain tumours and shows a poor prognosis with the five-year survival rate being less than 5%. After introducing the glioma pathogenesis and the limitation of current therapeutic strategies, we will discuss the potential impact of copper therapy and present the key results of the most relevant literature to establish a reliable foundation for future development of copper-based approaches.
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Pancreatic cancer has a poor prognosis due to its aggressive nature and ability to metastasize at an early stage. Currently, its management is still a challenge because this neoplasm is resistant to conventional treatment approaches, among which is chemo-radiotherapy (CRT), due to the abundant stromal compartment involved in the mechanism of hypoxia. Hyperthermia, among other effects, counteracts hypoxia by promoting blood perfusion and thereby can enhance the therapeutic effect of radiotherapy (RT). Therefore, the establishment of integrated treatments would be a promising strategy for the management of pancreatic carcinoma. Here, the effects of joint radiotherapy/hyperthermia (RT/HT) on optimized chick embryo chorioallantoic membrane (CAM) pancreatic tumor models are investigated. This model enables a thorough assessment of the tumor-arresting effect of the combined approach as well as the quantitative evaluation of hypoxia and cell cycle-associated mechanisms by both gene expression analysis and histology. The analysis of the lower CAM allows to investigate the variation of the metastatic behaviors of the cancer cells associated with the treatments. Overall, this study provides a potentially effective combined strategy for the non-invasive management of pancreatic carcinoma.
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Skin burns are debilitating injuries with significant morbidity and mortality associated with infections and sepsis, particularly in immunocompromised patients. In this context, nanotechnology can provide pioneering approaches for the topical treatment of burnt skin. Herein, the significant recovery of radiation-damaged skin by exploiting copper ultrasmall-in-nano architectures (CuNAs) dispersed in a home-made cosmetic cream is described and compared to other noble metals (such as gold). Owing to their peculiar design and components, CuNAs elicit a substantial recovery from burned skin in in vivo models after one topical application, and a significant anti-inflammatory effect is highlighted by reducing cytokine expression. The treatment exhibited neither significant toxicity nor the alteration of copper metabolism in the target organs because of the CuNA biocompatibility. This study may open new horizons in the treatment of radiation dermatitis and skin burns caused by other external events.
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Head and neck squamous cell carcinomas (HNSCCs) are a complex group of malignancies that affect different body sites pertaining to the oral cavity, pharynx and larynx. Current chemotherapy relies on platinum complexes, the major exponent being cisplatin, which exert severe side effects that can negatively affect prognosis. For this reason, other metal complexes with less severe side effects are being investigated as alternatives or adjuvants to platinum complexes. In this context, exploiting (supra)additive effects by the concurrent administration of cisplatin and emerging metal complexes is a promising research strategy that may lead to effective cancer management with reduced adverse reactions. Here, the combined action of cisplatin and a ruthenium(II) η6-arene compound (RuCy), both as free molecules and loaded into hybrid nano-architectures (NAs), has been assessed on HPV-negative HNSCC models of increasing complexity: 2D cell cultures, 3D multicellular tumor spheroids, and chorioallantoic membranes (CAMs). Two new NAs have been established to explore all the delivery combinations and compare their ability to enhance the efficacy of cisplatin in the treatment of HNSCCs. A significant supra-additive effect has been observed in both 2D and 3D models by one combination of treatments, suggesting that cisplatin is particularly effective when loaded on NAs, whereas RuCy performs better when administered as a free compound. Overall, this work paves the way for the establishment of the next co-chemotherapeutic approaches for the management of HNSCCs.
Asunto(s)
Carcinoma de Células Escamosas , Complejos de Coordinación , Neoplasias de Cabeza y Cuello , Humanos , Cisplatino/farmacología , Cisplatino/uso terapéutico , Carcinoma de Células Escamosas/patología , Complejos de Coordinación/farmacología , Complejos de Coordinación/uso terapéutico , Platino (Metal)/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológicoRESUMEN
Angiogenesis and metastasis are two interdependent cancer hallmarks, the latter of which is the key cause of treatment failure. Thus, establishing effective antiangiogenesis/antimetastasis agents is the final frontier in cancer research. Gold nanoparticles (GNPs) may provide disruptive advancements in this regard due to their intrinsic physical and physiological features. Here, we comprehensively discuss recent potential therapeutical strategies to treat angiogenesis and metastasis and present a critical review on the state-of-the-art in vitro and in vivo evaluations of the antiangiogenic/antimetastatic activity of GNPs. Finally, we provide perspectives on the contribution of GNPs to the advancement of cancer management.
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Antineoplásicos , Nanopartículas del Metal , Neoplasias , Humanos , Oro , Nanopartículas del Metal/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéuticoRESUMEN
The selective and localized delivery of active agents to neoplasms is crucial to enhance the chemotherapeutic efficacy while reducing the associated side effects. The encapsulation of chemotherapeutics in nanoparticles decorated with targeting agents is a strategy of special interest to improve drug delivery. However, serum protein adsorption often compromises the in vivo efficiency of targeting agents, leading to protein corona formation that interferes with the targeting process. Here, the enhanced efficacy of hybrid nano-architectures enclosing a platinum prodrug and decorated with a customized peptide (NAs-cisPt-Tf2) is demonstrated by employing alternative in vivo models of oral carcinoma. The peptide binds to transferrin and modulates the protein corona formation on NAs-cisPt-Tf2, supporting the identification of its receptor. Optimized chorioallantoic membrane cancer models (CAMs) enabled a thorough assessment of the tumor-suppressing effect of NAs-cisPt-Tf2 as well as the quantitative evaluation of angiogenesis and cell cycle associated mechanisms. The treatment strategy resulted in a significant tumor volume reduction coupled with anti-angiogenic and pro-apoptotic effects inferred from the downregulation of the vascular endothelial growth factor gene and increased expression of cleaved caspase-3. Overall, this study provides a potentially effective tumor-targeted approach for a non-invasive management of oral carcinoma.
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Antineoplásicos , Carcinoma , Nanopartículas , Profármacos , Corona de Proteínas , Humanos , Profármacos/farmacología , Platino (Metal) , Caspasa 3 , Factor A de Crecimiento Endotelial Vascular , Transferrina , Péptidos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular TumoralRESUMEN
The intranasal administration of drugs allows an effective and noninvasive therapeutic action on the respiratory tract. In an era of rapidly increasing antimicrobial resistance, new approaches to the treatment of communicable diseases, especially lung infections, are urgently needed. Metal nanoparticles are recognized as a potential last-line defense, but limited data on the biosafety and nano/biointeractions preclude their use. Here, we quantitatively and qualitatively assess the fate and the potential risks associated with the exposure to a silver nanomaterial model (i.e., silver ultrasmall-in-nano architectures, AgNAs) after a single dose instillation. Our results highlight that the biodistribution profile and the nano/biointeractions are critically influenced by both the design of the nanomaterial and the chemical nature of the metal. Overall, our data suggest that the instillation of rationally engineered nanomaterials might be exploited to develop future treatments for (non)communicable diseases of the respiratory tract.
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Nanopartículas del Metal , Nanoestructuras , Nanopartículas del Metal/uso terapéutico , Plata , Distribución TisularRESUMEN
Considering the dismal survival rate, novel therapeutic strategies are warranted to improve the outcome of pancreatic ductal adenocarcinoma (PDAC). Combining nanotechnology for delivery of chemotherapeutics-preferably radiosensitizing agents-is a promising approach to enhance the therapeutic efficacy of chemoradiation. We assessed the effect of biodegradable ultrasmall-in-nano architectures (NAs) containing gold ultra-small nanoparticles (USNPs) enclosed in silica shells loaded with cisplatin prodrug (NAs-cisPt) combined with ionizing radiation (IR). The cytotoxic effects and DNA damage induction were evaluated in PDAC cell lines (MIA PaCa2, SUIT2-028) and primary culture (PDAC3) in vitro and in the chorioallantoic membrane (CAM) in ovo model. Unlike NAs, NAs-cisPt affected the cell viability in MIA PaCa2 and SUIT2-028 cells. Furthermore, NAs-cisPt showed increased γH2AX expression up to 24 h post-IR and reduced ß-globin amplifications resulting in apoptosis induction at DNA and protein levels. Similarly, combined treatment of NAs-cisPt + IR in PDAC3 and SUIT2-028 CAM models showed enhanced DNA damage and apoptosis leading to tumor growth delay. Our results demonstrate an increased cytotoxic effect of NAs-cisPt, particularly through its release of the cisplatin prodrug. As cisplatin is a well-known radiosensitizer, administration of cisplatin prodrug in a controlled fashion through encapsulation is a promising new treatment approach which merits further investigation in combination with other radiosensitizing agents.
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The European Society for Medical Oncology (ESMO) suggests the use of chemotherapy as neoadjuvant, adjuvant, and concomitant to surgery and radiotherapy for the treatment of oral carcinoma by depending on the cancer stage. The usual drug of choice belongs to the platinum compounds. In this context, the evaluation of the cancer behavior associated with the administration of standard or emerging cisplatin compounds supports the establishment of optimal cancer management. Here, we have assessed and compared the performance of cisplatin alone and contained in biodegradable nanocapsules on standardized chorioallantoic membrane (CAM) tumor models. The vascularized environment and optimized grafting procedure allowed the establishment of solid tumors. The treatments showed antitumor and anti-angiogenic activities together with deregulation of pivotal genes responsible of treatment resistance and tumor aggressiveness. This study further supports the significance of CAM tumor models in oncological research for the comprehension of the molecular mechanisms involved in tumor treatment response.
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Many efforts have recently concentrated on constructing and developing nanoparticles (NPs) as promising thermal agent for optical hyperthermia and photothermal therapy. However, thermal energy transfer in biological tissue is a complex process involving different mechanisms such as conduction, convection, radiation. Therefore, having information about thermal properties of tissue especially when NPs are embedded in is a necessity for predicting the heat transfer during hyperthermia. In this work, the thermal properties of solid phantom based on agar in the presence of three different nanoparticles (BPSi, tNAs, GNRs) and alone were measured and reported as a function of temperature (ranging from 22 to 62 °C). The thermal response of these NPs to an 808 nm laser beam with three different powers were studied in the water comparatively. Agar and tNAs have almost constant thermal properties in the considered range. Among the three NPs, gold has the highest conductivity and diffusivity. At 62 °C BPSi NPs have the similar amount of increase for the diffusivity. The thermal parameters reported in this paper can be useful for the mathematical modeling. Irradiation of the NPs-loaded water phantom displayed the highest radiosensitivity of gold among the three mentioned NPs. However, for the higher power of irradiation, BPSi and tNAs NPs showed the increased absorption of heat during shorter time and the increased temperature gradient slope for the initial 15 s after the irradiation started. The three NPs showed different thermal and irradiation response behavior; however, this comparison study notes the worth of having information about thermal parameters of NPs-loaded tissue for pre-clinical planning.
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With the aim of preparing hybrid hydrogels suitable for use as patches for the local treatment of squamous cell carcinoma (SCC)-affected areas, curcumin (CUR) was loaded onto graphene oxide (GO) nanosheets, which were then blended into an alginate hydrogel that was crosslinked by means of calcium ions. The homogeneous incorporation of GO within the polymer network, which was confirmed through morphological investigations, improved the stability of the hybrid system compared to blank hydrogels. The weight loss in the 100-170 °C temperature range was reduced from 30% to 20%, and the degradation of alginate chains shifted to higher temperatures. Moreover, GO enhanced the stability in water media by counteracting the de-crosslinking process of the polymer network. Cell viability assays showed that the loading of CUR (2.5% and 5% by weight) was able to reduce the intrinsic toxicity of GO towards healthy cells, while higher amounts were ineffective due to the antioxidant/prooxidant paradox. Interestingly, the CUR-loaded systems were found to possess a strong cytotoxic effect in SCC cancer cells, and the sustained CUR release (~50% after 96 h) allowed long-term anticancer efficiency to be hypothesized.
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Surgical site infection (SSI) substantially contributes each year to patients' morbidity and mortality, accounting for about 15% of all nosocomial infections. SSI drastically increases the rehab stint and expenses while jeopardizing health outcomes. Besides prevention, the treatment regime relies on an adequate antibiotic therapy. On the other hand, resistant bacterial strains have currently reached up to 34.3% of the total infections, and this percentage grows annually, reducing the efficacy of the common treatment schemes. Thus, new antibacterial strategies are urgently demanded. Here, we demonstrated in rats the effectiveness of non-persistent silver nano-architectures (AgNAs) in infected wound healing together with their synergistic action in combination with chlorhexidine. Besides the in vivo efficacy evaluation, we performed analysis of the bacteriological profile of purulent wound, histological evaluations, and macrophages polarization quantifications to further validate our findings and elucidate the possible mechanisms of AgNAs action on wound healing. These findings open the way for the composition of robust multifunctional nanoplatforms for the translation of safe and efficient topical treatments of SSI.
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Preclinical cancer research increasingly demands sophisticated models for the development and translation of efficient and safe cancer treatments to clinical practice. In this regard, tumor-grafted chorioallantoic membrane (CAM) models are biological platforms that account for the dynamic roles of the tumor microenvironment and cancer physiopathology, allowing straightforward investigations in agreement to the 3Rs concept (the concept of reduction, refinement, and replacement of animal models). CAM models are the next advanced model for tumor biological explorations as well as for reliable assessment regarding initial efficacy, toxicity, and systemic biokinetics of conventional and emerging neoplasm treatment modalities. Here we report a standardized and optimized protocol for the production and biocharacterization of human papillomavirus (HPV)-negative head and neck chick chorioallantoic membrane models from a commercial cell line (SCC-25). Oral malignancies continue to have severe morbidity with less than 50% long-term survival despite the advancement in the available therapies. Thus, there is a persisting demand for new management approaches to establish more efficient strategies toward their treatment. Remarkably, the inclusion of CAM models in the preclinical research workflow is crucial to ethically foster both the basic and translational oncological research on oral malignancies as well as for the advancement of efficient cancer treatment approaches.
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The constant advent of major health threats such as antibacterial resistance or highly communicable viruses, together with a declining antimicrobial discovery, urgently requires the exploration of innovative therapeutic approaches. Nowadays, strategies based on metal nanoparticle technology have demonstrated interesting outcomes due to their intrinsic features. In this scenario, there is an emerging and growing interest in copper-based nanoparticles (CuNPs). Indeed, in their pure metallic form, as oxides, or in combination with sulfur, CuNPs have peculiar behaviors that result in effective antimicrobial activity associated with the stimulation of essential body functions. Here, we present a critical review on the state of the art regarding the in vitro and in vivo evaluations of the antimicrobial activity of CuNPs together with absorption, distribution, metabolism, excretion, and toxicity (ADMET) assessments. Considering the potentiality of CuNPs in antimicrobial treatments, within this Review we encounter the need to summarize the behaviors of CuNPs and provide the expected perspectives on their contributions to infectious and communicable disease management.
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Antiinfecciosos , Nanopartículas del Metal , Antibacterianos/farmacología , Antiinfecciosos/farmacologíaRESUMEN
Diffuse Intrinsic Pontine Gliomas (DIPGs) are highly aggressive paediatric brain tumours. Currently, irradiation is the only standard treatment, but is palliative in nature and most patients die within 12 months of diagnosis. Novel therapeutic approaches are urgently needed for the treatment of this devastating disease. We have developed non-persistent gold nano-architectures (NAs) functionalised with human serum albumin (HSA) for the delivery of doxorubicin. Doxorubicin has been previously reported to be cytotoxic in DIPG cells. In this study, we have preclinically evaluated the cytotoxic efficacy of doxorubicin delivered through gold nanoarchitectures (NAs-HSA-Dox). We found that DIPG neurospheres were equally sensitive to doxorubicin and doxorubicin-loaded NAs. Colony formation assays demonstrated greater potency of NAs-HSA-Dox on colony formation compared to doxorubicin. Western blot analysis indicated increased apoptotic markers cleaved Parp, cleaved caspase 3 and phosphorylated H2AX in NAs-HSA-Dox treated DIPG neurospheres. Live cell content and confocal imaging demonstrated significantly higher uptake of NAs-HSA-Dox into DIPG neurospheres compared to doxorubicin alone. Despite the potency of the NAs in vitro, treatment of an orthotopic model of DIPG showed no antitumour effect. This disparate outcome may be due to the integrity of the blood-brain barrier and highlights the need to develop therapies to enhance penetration of drugs into DIPG.