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Anticancer chemo-immunotherapy has gained considerable attention across various scientific domains as a prospective approach for the comprehensive eradication of malignant tumors. Recent research has particularly been focused on traditional anthracycline chemo drugs, such as doxorubicin and mitoxantrone. These compounds trigger apoptosis in tumor cells and evoke immunogenic cell death (ICD). ICD is a pivotal initiator of the cancer-immunity cycle by facilitating the release of damage-associated molecular patterns (DAMPs). The resultant DAMPs released from cancer cells effectively activate the immune system, resulting in an increase in tumor-infiltrating T cells. In this study, we have innovated a co-delivery strategy involving folate-modified liposomes to deliver doxorubicin and monophosphoryl lipid A (MPLA) simultaneously to tumor tissue. The engineered liposomes exploit the overexpression of folate receptors within the tumor tissues. Delivered doxorubicin initiates ICD at the tumor cells, further enhancing the immunogenic stimulus. Additionally, MPLA helps T cell priming by activating antigen-presenting cells. This intricate interplay culminates in a synergistic effect, ultimately resulting in an augmented and potentiated anticancer chemo-immunotherapeutic liposomal treatment.
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Doxorrubicina , Muerte Celular Inmunogénica , Inmunoterapia , Lípido A , Liposomas , Receptor Toll-Like 4 , Liposomas/química , Doxorrubicina/farmacología , Doxorrubicina/química , Animales , Muerte Celular Inmunogénica/efectos de los fármacos , Humanos , Receptor Toll-Like 4/agonistas , Receptor Toll-Like 4/metabolismo , Ratones , Lípido A/análogos & derivados , Lípido A/química , Lípido A/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/terapia , Línea Celular Tumoral , Femenino , Antineoplásicos/química , Antineoplásicos/farmacología , Ácido Fólico/químicaRESUMEN
Activating the glucagon-like peptide-1 (GLP-1) receptor by oral nucleic acid delivery would be a promising treatment strategy against hyperglycemia due to its various therapeutic actions. However, GLP-1 receptor agonists are effective only in subcutaneous injections because they face multiple barriers due to harsh gastrointestinal tract (GIT) conditions before reaching the site of action. The apical sodium bile acid transporter (ASBT) pathway at the intestinal site could be an attractive target to overcome the problem. Herein, we used our previously established multimodal carrier system utilizing bile salt, protamine sulfate, and calcium phosphate as excipients (PTCA) and the GLP-1 gene as an active ingredient (GENE) to test the effects of different formulation doses against diabetes and obesity. The carrier system demonstrated the ability to protect the GLP-1 model gene encoded within the plasmid at the GIT and transport it via ASBT at the target site. A single oral dose, regardless of quantity, showed the generation of GLP-1 and insulin from the body and maintained the normoglycemic condition by improving insulin sensitivity and blood sugar tolerance for a prolonged period. This oral gene therapy approach shows significantly higher therapeutic efficacy in preclinical studies than currently available US Food and Drug Administration-approved GLP-1 receptor agonists such as semaglutide and liraglutide. Also, a single oral dose of GENE/PTCA is more effective than 20 insulin injections. Our study suggests that oral GENE/PTCA formulation could be a promising alternative to injection-based therapeutics for diabetics, which is effective in long-term treatment and has been found to be highly safe in all aspects of toxicology.
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Breast cancer is the most prevalent cancer among women and the leading cause of cancer-related deaths in this population. Recent advances in Immunotherapy, or combined immunotherapy, offering a more targeted and less toxic approach, expand the survival rate of patients more than conventional treatment. Notably, hydrogels, a versatile platform provided promising avenues to combat breast cancer in preclinical studies and extended to clinical practices. With advantages such as the alternation of tumor microenvironment, immunomodulation, targeted delivery of therapeutic agents, and their sustained release at specific sites of interest, hydrogels can potentially be used for the treatment of breast cancer. This review highlights the advantages, mechanisms of action, stimuli-responsiveness properties, and recent advancements of hydrogels for treating breast cancer immunotherapy. Moreover, post-treatment and its clinical translations are discussed in this review. The integration of hydrogels in immunotherapy strategies may pave the way for more effective, personalized, and patient-friendly approaches to combat breast cancer, ultimately contributing to a brighter future for breast cancer patients.
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Neoplasias de la Mama , Hidrogeles , Inmunoterapia , Hidrogeles/química , Hidrogeles/administración & dosificación , Humanos , Neoplasias de la Mama/terapia , Neoplasias de la Mama/inmunología , Femenino , Inmunoterapia/métodos , Animales , Microambiente Tumoral , Sistemas de Liberación de MedicamentosRESUMEN
INTRODUCTION: Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type 2 diabetes mellitus (T2DM) in clinical practice. METHODS: This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week 24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks 12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48 weeks from baseline, and safety. RESULTS: We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48 weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30-90 mL/min/1.73 m2, glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5 years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24 weeks. CONCLUSION: Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function. TRIAL REGISTRATION NUMBER: NCT05107063 submitted October 27, 2021.
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Diabetes Mellitus Tipo 2 , Dislipidemias , Tasa de Filtración Glomerular , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Pravastatina , Humanos , Pravastatina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Dislipidemias/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Tasa de Filtración Glomerular/efectos de los fármacos , Estudios Prospectivos , Anciano , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , República de Corea , Adulto , Riñón/efectos de los fármacos , Riñón/fisiopatologíaRESUMEN
Upregulation of PRAME (preferentially expressed antigen of melanoma) has been implicated in the progression of a variety of cancers, including melanoma. The tumor suppressor p53 is a transcriptional regulator that mediates cell cycle arrest and apoptosis in response to stress signals. Here, we report that PRAME is a novel repressive target of p53. This was supported by analysis of melanoma cell lines carrying wild-type p53 and human melanoma databases. mRNA expression of PRAME was downregulated by p53 overexpression and activation using DNA-damaging agents, but upregulated by p53 depletion. We identified a p53-responsive element (p53RE) in the promoter region of PRAME. Luciferase and ChIP assays showed that p53 represses the transcriptional activity of the PRAME promoter and is recruited to the p53RE together with HDAC1 upon etoposide treatment. The functional significance of p53 activationmediated PRAME downregulation was demonstrated by measuring colony formation and p27 expression in melanoma cells. These data suggest that p53 activation, which leads to PRAME downregulation, could be a therapeutic strategy in melanoma cells. [BMB Reports 2024; 57(6): 299-304].
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Antígenos de Neoplasias , Melanoma , Regiones Promotoras Genéticas , Proteína p53 Supresora de Tumor , Humanos , Proteína p53 Supresora de Tumor/metabolismo , Melanoma/metabolismo , Melanoma/genética , Melanoma/patología , Antígenos de Neoplasias/metabolismo , Antígenos de Neoplasias/genética , Línea Celular Tumoral , Regiones Promotoras Genéticas/genética , Regulación Neoplásica de la Expresión Génica , Etopósido/farmacología , Histona Desacetilasa 1/metabolismo , Regulación hacia Abajo/efectos de los fármacosRESUMEN
Catechol-based biomaterials demonstrate biocompatibility, making them suitable for a wide range of therapeutic applications when integrated into various molecular frameworks. However, the development of orally available catechol-based biomaterials has been hindered by significant pH variations and complex interactions in the gastrointestinal (GI) tract. In this study, we introduce a novel catechol-modified bile acid (CMBA), which is synthesized by anchoring the FDA-approved drug, ursodeoxycholic acid to the neurotransmitter dopamine. This modification could form a new apical sodium-dependent bile acid transporter (ASBT) inhibitor (ASBTi) due to the bile acid moiety. The computational analysis using the TRAnsient Pockets in Proteins (TRAPP) module, coupled with MD simulations, revealed that CMBA exhibits a strong binding affinity at residues 51-55 of ASBT with a low inhibitory constant (Ki) value. Notably, in slightly alkaline biological conditions, CMBA molecules self-assemble into carrier-free nanoparticles with an average size of 240.2 ± 44.2 nm, while maintaining their ability to bind with ASBT. When administered orally, CMBA accumulates in the ileum and liver over 24 h, exhibiting significant therapeutic effects on bile acid (BA) metabolism in a high-fat diet (HFD)-fed mouse model. This study underscores the therapeutic potential of the newly developed catechol-based, pH-responsive ASBT-inhibiting nanoparticles presenting a promising avenue for advancing therapy.
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Ácidos y Sales Biliares , Catecoles , Nanopartículas , Transportadores de Anión Orgánico Sodio-Dependiente , Animales , Catecoles/química , Catecoles/metabolismo , Concentración de Iones de Hidrógeno , Ácidos y Sales Biliares/metabolismo , Ácidos y Sales Biliares/química , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Nanopartículas/química , Ratones , Humanos , Simportadores/metabolismo , Masculino , Ratones Endogámicos C57BLRESUMEN
This study seeks to evaluate the ability of machine learning methods to predict the dry weight of chronic hemodialysis athletes. The researcher has reached out to kidney patients who have had to give up sports and athletic careers due to chronic hemodialysis. This paper explores the development of medical prediction algorithms that combine image analysis with numerical data, which is widely used in the field of medicine. This deep learning method is widely employed to enhance the treatment of athletes who have kidney conditions. Regular hemodialysis is crucial for maintaining the health of athletes who have kidney disease. Accurately predicting dry weight is a crucial step in the process of performing hemodialysis. In this context, dry weight refers to the optimal moisture level at which excess water is effectively eliminated from the patient (athletes) through ultrafiltration during hemodialysis. In order to accurately determine the optimal amount of hemodialysis, predicting the correct dry weight is crucial. However, this task is quite challenging and often yields inaccurate results due to the extensive data analysis required by experienced nephrologists. This paper presents a deep learning methodology utilising the Artificial Neural Network (ANN) approach to efficiently address these issues. The proposed method aims to predict dry weight rapidly by analysing image values and clinical data from X-ray images obtained during routine check-ups. The current study has several theoretical and practical implications. This study contributes to the existing literature on chronic hemodialysis and the dry weight of athletes, offering valuable insights to sports health organisations. By doing so, these organisations can effectively prepare to proactively evaluate the atypical health conditions of athletes.(AU)
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Humanos , Masculino , Femenino , Atletas , Psicología del Deporte , Deportes , Medicina Deportiva , Diálisis Renal , Aprendizaje AutomáticoRESUMEN
Over the last decades, ionic liquids (IL) have shown great potential in non-invasive delivery starting from synthetic small molecules to biological large molecules. ILs are emerging as a particular class of drug delivery systems due to their unique physiochemical properties, simple surface modification, and functionalization. These features of IL help achieve specific design principles that are essential for a non-invasive drug delivery system. In this review, we have discussed IL and their applications in non-invasive drug delivery systems. We evaluated state-of-the-art development and advances of IL aiming to mitigate the biological and physical barriers to improve transdermal and oral delivery, summarized in this review. We also provided an overview of the various factors determining the systemic transportation of IL-based formulation. Additionally, we have emphasized how the ILs facilitate the transportation of therapeutic molecules by overcoming biological barriers.
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Líquidos Iónicos , Humanos , Líquidos Iónicos/química , Sistemas de Liberación de Medicamentos , Administración CutáneaRESUMEN
OBJECTIVE: Hypoglycemia is a frequent occurrence in chronic kidney disease patients due to alterations in glucose and insulin metabolism. However, there are sparse data examining the predictors and clinical implications of hypoglycemia including mortality risk among incident hemodialysis patients. DESIGN AND METHODS: Among 58,304 incident hemodialysis patients receiving care from a large national dialysis organization over 2007-2011, we examined clinical characteristics associated with risk of hypoglycemia, defined as a blood glucose concentration <70 mg/dL, in the first year of dialysis using expanded case-mix + laboratory logistic regression models. We then examined the association between hypoglycemia during the first year of dialysis with all-cause mortality using expanded case-mix + laboratory Cox models. RESULTS: In the first year of dialysis, hypoglycemia was observed among 16.8% of diabetic and 6.9% of nondiabetic incident hemodialysis patients. In adjusted logistic regression models, clinical characteristics associated with hypoglycemia included younger age, female sex, African-American race, presence of a central venous catheter, lower residual renal function, and longer dialysis session length. In the overall cohort, patients who experienced hypoglycemia had a higher risk of all-cause mortality risk (reference: absence of hypoglycemia): adjusted hazard ratio (95% confidence interval) 1.08 (1.04, 1.13). In stratified analyses, hypoglycemia was also associated with higher mortality risk in the diabetic and nondiabetic subgroups: adjusted hazard ratios (95% confidence interval's) 1.08 (1.04-1.13), and 1.17 (0.94-1.45), respectively. CONCLUSIONS: Hypoglycemia was a frequent occurrence among both diabetic and nondiabetic hemodialysis patients and was associated with a higher mortality risk. Further studies are needed to identify approaches that reduce hypoglycemia risk in the hemodialysis population.
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Recent studies indicate that mitochondrial dysfunctions and DNA damage have a critical influence on cell survival, which is considered one of the therapeutic targets for cancer therapy. In this study, we demonstrated a comparative study of the effect of polyphenolic carbon quantum dots (CQDs) on in vitro and in vivo antitumor efficacy. Dual emissive (green and yellow) shape specific polyphenolic CQDs (G-CQDs and Y-CQDs) were synthesized from easily available nontoxic precursors (phloroglucinol), and the antitumor property of the as-synthesized probe was investigated as compared to round-shaped blue emissive CQDs (B-CQDs) derived from well-reported precursor citric acid and urea. The B-CQDs had a nuclei-targeting property, and G-CQDs and Y-CQDs had mitochondria-targeting properties. We have found that the polyphenol containing CQDs (at a dose of 100 µg mL-1) specifically attack mitochondria by excess accumulation, altering the metabolism, inhibiting branching pattern, imbalanced Bax/Bcl-2 homeostasis, and ultimately generating oxidative stress levels, leading to oxidative stress-induced cell death in cancer cells in vitro. We show that G-CQDs are the main cause of oxidative stress in cancer cells because of their ability to produce sufficient â¢OH- and 1O2 radicals, evidenced by electron paramagnetic resonance spectroscopy and a terephthalic acid test. Moreover, the near-infrared absorption properties of the CQDs were exhibited in two-photon (TP) emission, which was utilized for TP cellular imaging of cancer cells without photobleaching. The in vivo antitumor test further discloses that intratumoral injection of G-CQDs can significantly augment the treatment efficacy of subcutaneous tumors without any adverse effects on BalB/c nude mice. We believe that shape-specific polyphenolic CQD-based nanotheranostic agents have a potential role in tumor therapy, thus proving an insight on treatment of malignant cancers.
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Radiopharmaceutical therapy, which can detect and treat tumours simultaneously, was introduced more than 80 years ago, and it has changed medical strategies with respect to cancer. Many radioactive radionuclides have been developed, and functional, molecularly modified radiolabelled peptides have been used to produce biomolecules and therapeutics that are vastly utilised in the field of radio medicine. Since the 1990s, they have smoothly transitioned into clinical application, and as of today, a wide variety of radiolabelled radionuclide derivatives have been examined and evaluated in various studies. Advanced technologies, such as conjugation of functional peptides or incorporation of radionuclides into chelating ligands, have been developed for advanced radiopharmaceutical cancer therapy. New radiolabelled conjugates for targeted radiotherapy have been designed to deliver radiation directly to cancer cells with improved specificity and minimal damage to the surrounding normal tissue. The development of new theragnostic radionuclides, which can be used for both imaging and therapy purposes, allows for more precise targeting and monitoring of the treatment response. The increased use of peptide receptor radionuclide therapy (PRRT) is also important in the targeting of specific receptors which are overexpressed in cancer cells. In this review, we provide insights into the development of radionuclides and functional radiolabelled peptides, give a brief background, and describe their transition into clinical application.
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Combined cancer immunotherapy has demonstrated promising potential with an amplified antitumor response and immunosuppressive tumor microenvironment (TME) modulation. However, one of the main issues that cause treatment failure is the poor diffusion and insufficient penetration of therapeutic and immunomodulatory agents in solid tumors. Herein, a cancer treatment approach that combines photothermal therapy (PTT) and nitric oxide (NO) gas therapy for tumor extracellular matrix (ECM) degradation, along with NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor that reduces tryptophan catabolism to kynurenine, and DMXAA, a stimulator of interferon gene (STING) agonist that stimulates antigen cross-presentation, is proposed to overcome this issue. Upon NIR (808 nm) laser irradiation, NO-GEL achieved the desired thermal ablation by releasing sufficient tumor antigens through immunogenic cell death (ICD). NO delivery triggered local diffusion of excess NO gas for effectively degrading tumor collagen in the ECM, homogeneously delivered NLG919 throughout the tumor tissue, inhibited IDO expression that was upregulated by PTT, and reduced the immune suppressive activities. The sustained release of DMXAA prolonged dendritic cell maturation and CD8+ T cell activation against the tumor. In summary, NO-GEL therapeutics offer a significant tumor regression with PTT and STING agonist combination that stimulates a durable antitumor immune response. Additional unification of IDO inhibition during PTT supplements the immunotherapy by reducing the T cell apoptosis and immune suppressive cell infiltration to TME. NO-GEL with the STING agonist and IDO inhibitor is an effective therapeutic combination to counter possible limitations during solid tumor immunotherapy.
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BACKGROUND: Graphene-based nanomaterials possess unique optical, physicochemical and biomedical properties which make them potential tools for imaging and therapy. Manganese oxide nanoparticles are attractive candidates for contrast agents in magnetic resonance imagint (MRI). We used manganese oxide (Mn3O4) and highly reduced graphene oxide (HRG) to synthesize hybrid nanoparticles (HRG-Mn3O4) and tested their efficacy for photodynamic therapy (PDT) in breast cancer cells. METHODS: The newly synthesized nanoparticles were characterized by transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) spectroscopy, UV-visible spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetry, and X-ray diffraction (XRD) analyses. We used standard protocols of cytotoxicity and PDT after exposing A549 cells to various concentrations of hybrid nanoparticles (HRG-Mn3O4). We also performed fluorescence microscopy for live/dead cellular analysis. A549 cells were incubated with nanoparticles for 24 h and stained with fluorescein diacetate (green emission for live cells) and propidium iodide (red emission for dead cells) to visualize live and dead cells, respectively. RESULTS: The cell viability analysis showed that more than 98% of A549 cells survived even after the exposure of a high concentration (100 µg/mL) of nanomaterials. These results confirmed that the HRG-Mn3O4 nanoparticles are nontoxic and biocompatible at physiological conditions. When the cell viability analysis was performed after laser irradiation, we observed significant and concentration-dependent cytotoxicity of HRG-Mn3O4 as compared to Mn3O4 nanoparticles. Fluorescence microscopy showed that almost 100% cells were viable when treated with phosphate buffered saline or Mn3O4 while only few dead cells were detected after exposure of HRG-Mn3O4 nanoparticles. However, laser irradiation resulted in massive cellular damage by HRG-Mn3O4 nanoparticles which was directly related to the generation of reactive oxygen species (ROS). CONCLUSIONS: HRG-Mn3O4 hybrid nanoparticles are stable, biocompatible, nontoxic, and possess therapeutic potential for photodynamic therapy of cancer. Further studies are warranted to explore the MRI imaging ability of these nanomaterials using animal models of cancer.
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Grafito , Nanopartículas , Fotoquimioterapia , Animales , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
The deposition of monosodium urate (MSU) crystals induces the overexpression of reactive oxygen species (ROS) and proinflammatory cytokines in residential macrophages, further promoting the infiltration of inflammatory leukocytes in the joints of gouty arthritis. Herein, a peroxidase-mimicking nanoscavenger was developed by forming manganese dioxide over albumin nanoparticles loaded with an anti-inflammatory drug, indomethacin (BIM), to block the secretion of ROS and COX2-induced proinflammatory cytokines in the MSU-induced gouty arthritis model. In the MSU-induced arthritis mouse model, the BIM nanoparticles alleviated joint swelling, which is attributed to the abrogation of ROS and inflammatory cytokine secretions from proinflammatory macrophages that induces neutrophil infiltration and fluid building up in the inflammation site. Further, the BIM nanoparticle treatment reduced the influx of macrophages and neutrophils in the injured region by blocking migration and inducing reverse migration in the zebrafish larva tail amputation model as well as in MSU-induced peritonitis and air pouch mouse models. Overall, the current strategy of employing biomineralized nanoscavengers for arthritis demonstrates clinical significance in dual blocking of peroxides and COX2 to prevent influx of inflammatory cells into the sites of inflammation.
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Artritis Gotosa , Animales , Ratones , Artritis Gotosa/inducido químicamente , Artritis Gotosa/tratamiento farmacológico , Neutrófilos , Especies Reactivas de Oxígeno/efectos adversos , Pez Cebra , Ciclooxigenasa 2 , Ácido Úrico , Inflamación/tratamiento farmacológico , Inflamación/inducido químicamente , Citocinas , Macrófagos , Modelos Animales de EnfermedadRESUMEN
Exosomes are endosome-derived nanovesicles involved in cellular communication. They are natural nanocarriers secreted by various cells, making them suitable candidates for diverse drug delivery and therapeutic applications from a material standpoint. They have a phospholipid bilayer decorated with functional molecules and an enclosed parental matrix, which has attracted interest in developing designer/hybrid engineered exosome nanocarriers. The structural versatility of exosomes allows the modification of their original configuration using various methods, including genetic engineering, chemical procedures, physical techniques, and microfluidic technology, to load exosomes with additional cargo for expanded biomedical applications. Exosomes show enormous potential for overcoming the limitations of conventional nanoparticle-based techniques in targeted therapy. This review highlights the exosome sources, characteristics, state of the art in the field of hybrid exosomes, exosome-like nanovesicles and engineered exosomes as potential cargo delivery vehicles for therapeutic applications.
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Exosomas , Nanopartículas , Exosomas/química , Sistemas de Liberación de Medicamentos , Endosomas , Ingeniería GenéticaRESUMEN
As extracellular vesicle (EV)-based nanotechnology has developed rapidly, it has made unprecedented opportunities for nanomedicine possible. EVs and exosome-like nanovesicles (ELNVs) are natural nanocarriers with unique structural, compositional, and morphological characteristics that provide excellent physical, chemical, and biochemical properties. In this literature, we examine the characteristics of EVs, including how they are administered orally and their therapeutic activity. According to the current examples of EVs and ELNVs for oral delivery, milk and plant EVs can exert therapeutic effects through their protein, nucleic acid, and lipid components. Furthermore, several methods for loading drugs into exosomes and targeting exosomes have been employed to investigate their therapeutic capability. Moreover, we discuss EVs as potential drug carriers and the potential role of ELNVs for disease prevention and treatment or as potential drug carriers in the future. In conclusion, the issues associated with the development of EVs and ELNVs from sources such as milk and plants, as well as concerns with standardized applications of these EVs, are discussed.
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Cancer is the leading cause of death after cardiovascular disease. Despite significant advances in cancer research over the past few decades, it is almost impossible to cure end-stage cancer patients and bring them to remission. Adverse effects of chemotherapy are mainly caused by the accumulation of chemotherapeutic agents in normal tissues, and drug resistance hinders the potential therapeutic effects and curing of this disease. New drug formulations need to be developed to overcome these problems and increase the therapeutic index of chemotherapeutics. As a chemotherapeutic delivery platform, three-dimensional (3D) scaffolds are an up-and-coming option because they can respond to biological factors, modify their properties accordingly, and promote site-specific chemotherapeutic deliveries in a sustainable and controlled release manner. This review paper focuses on the features and applications of the variety of 3D scaffold-based nano-delivery systems that could be used to improve local cancer therapy by selectively delivering chemotherapeutics to the target sites in future.
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Cancer is a leading cause of death worldwide. Conventional methods of cancer treatment, including chemotherapy and radiotherapy, are associated with multiple side effects. Recently, photodynamic therapy (PDT) has emerged as an effective therapeutic modality for cancer treatment without adversely affecting normal tissue. In this study, we synthesized nitrogen doped graphene (NDG) and conjugated it with Mn3O4 nanoparticles to produce NDG-Mn3O4 nanocomposite with the aim of testing its bimodal performance including PDT and magnetic resonance imaging (MRI). We did not use any linker or binder for conjugation between NDG and Mn3O4, rather they were anchored by a milling process. The results of cell viability analysis showed that NDG-Mn3O4 nanocomposites caused significant cell death under laser irradiation, while control and Mn3O4 nanoparticles showed negligible cell death. We observed increased generation of singlet oxygen after exposure of NDG-Mn3O4 nanocomposites, which was directly proportional to the duration of laser irradiation. The results of MRI showed concentration dependent enhancement of signal intensity with an increasing concentration of NDG-Mn3O4 nanocomposites. In conclusion, NDG-Mn3O4 nanocomposites did not cause any cytotoxicity under physiological conditions. However, they produced significant and dose-dependent cytotoxicity in cancer cells after laser irradiation. NDG-Mn3O4 nanocomposites also exhibited concentration-dependent MRI contrast property, suggesting their possible application for cancer imaging. Further studies are warranted to test the theranostic potential of NDG-Mn3O4 nanocomposites using animal models of cancer.
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Nanocompuestos , Fotoquimioterapia , Animales , Línea Celular Tumoral , Fotoquimioterapia/métodos , Nanocompuestos/uso terapéutico , Imagen por Resonancia Magnética , Óxidos de Nitrógeno , NitrógenoRESUMEN
Flagella and cilia are slender structures that serve important functionalities in the microscopic world through their locomotion induced by fluid and structure interaction. With recent developments in microscopy, fabrication, biology, and modeling capability, robots inspired by the locomotion of these organelles in low Reynolds number flow have been manufactured and tested on the micro-and macro-scale, ranging from medicalin vivomicrobots, microfluidics to macro prototypes. We present a collection of modeling theories, control principles, and fabrication methods for flagellated and ciliary robots.