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1.
Nat Commun ; 15(1): 6058, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39025877

RESUMEN

Heart failure causes considerable morbidity and mortality worldwide. Clinically applied drugs for the treatment of heart failure are still severely limited by poor delivery efficiency to the heart and off-target consumption. Inspired by the high heart delivery efficiency of inhaled drugs, we present an inhalable cardiac-targeting peptide (CTP)-modified calcium phosphate (CaP) nanoparticle for the delivery of TP-10, a selective inhibitor of PDE10A. The CTP modification significantly promotes cardiomyocyte and fibroblast targeting during the pathological state of heart failure in male mice. TP-10 is subsequently released from TP-10@CaP-CTP and effectively attenuates cardiac remodelling and improved cardiac function. In view of these results, a low dosage (2.5 mg/kg/2 days) of inhaled medication exerted good therapeutic effects without causing severe lung injury after long-term treatment. In addition, the mechanism underlying the amelioration of heart failure is investigated, and the results reveal that the therapeutic effects of this system on cardiomyocytes and cardiac fibroblasts are mainly mediated through the cAMP/AMPK and cGMP/PKG signalling pathways. By demonstrating the targeting capacity of CTP and verifying the biosafety of inhalable CaP nanoparticles in the lung, this work provides a perspective for exploring myocardium-targeted therapy and presents a promising clinical strategy for the long-term management of heart failure.


Asunto(s)
Insuficiencia Cardíaca , Miocitos Cardíacos , Nanomedicina , Nanopartículas , Animales , Masculino , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/prevención & control , Ratones , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Administración por Inhalación , Nanopartículas/química , Nanomedicina/métodos , Péptidos/farmacología , Péptidos/administración & dosificación , Miocardio/metabolismo , Miocardio/patología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , GMP Cíclico/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Modelos Animales de Enfermedad , Fosfatos de Calcio
2.
Adv Pharmacol ; 100: 119-155, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39034050

RESUMEN

Drug discovery is challenging task with numerous obstacles in translating drug candidates into clinical products. Dendrimers are highly adaptable nanostructured polymers with significant potential to improve the chances of clinical success for drugs. Yet, dendrimer-based drug products are still in their infancy. However, Hydroxyl polyamidoamine (PAMAM) dendrimers showed significant promise in drug discovery efforts, owning their remarkable potential to selectively target and deliver drugs specifically to activated microglia and astrocytes at the site of brain injury in several preclinical models. After a decade's worth of academic research and pre-clinical efforts, the hydroxyl PAMAM dendrimer-N-acetyl cysteine conjugate (OP-101) nanomedicine has made a significant advancement in the field of nanomedicine and targeted delivery. The OP-101 conjugate, primarily developed and validated in academic labs, has now entered clinical trials as a potential treatment for hyperinflammation in hospitalized adults with severe COVID-19 through Ashvattha Therapeutics. This chapter, we delve into the journey of the hydroxyl PAMAM dendrimer-N-acetylcysteine (NAC) OP-101 formulation from the laboratory to the clinic. It will specifically focus on the design, synthesis, preclinical, and clinical development of OP-101, highlighting the potential it holds for the future of medicine and the positive Phase 2a results for treating severe COVID-19.


Asunto(s)
Acetilcisteína , Dendrímeros , Nanomedicina , Dendrímeros/química , Acetilcisteína/farmacología , Acetilcisteína/uso terapéutico , Acetilcisteína/química , Humanos , Animales , Nanomedicina/métodos , Tratamiento Farmacológico de COVID-19 , Sistemas de Liberación de Medicamentos/métodos , Desarrollo de Medicamentos/métodos
3.
Phys Rev E ; 109(6-2): 065309, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39020899

RESUMEN

Magnetic nanoparticles have emerged as a promising approach to improving cancer treatment. However, many nanoparticle designs fail in clinical trials due to a lack of understanding of how to overcome the in vivo transport barriers. To address this shortcoming, we develop a computational model aimed at the study of magnetic nanoparticles in vitro and in vivo. In this paper, we present an important building block for this overall goal, namely an efficient computational model of the in-flow capture of magnetic nanoparticles by a cylindrical permanent magnet in an idealized test setup. We use a continuum approach based on the Smoluchowski advection-diffusion equation, combined with a simple approach to consider the capture at an impenetrable boundary, and derive an analytical expression for the magnetic force of a cylindrical magnet of finite length on the nanoparticles. This provides a simple and numerically efficient way to study different magnet configurations and their influence on the nanoparticle distribution in three dimensions. Such an in silico model can increase insight into the underlying physics, help to design prototypes, and serve as a precursor to more complex systems in vivo and in silico.


Asunto(s)
Simulación por Computador , Nanopartículas de Magnetita , Nanomedicina , Neoplasias , Neoplasias/terapia , Nanopartículas de Magnetita/química , Imanes/química , Humanos
4.
J Transl Med ; 22(1): 648, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38987805

RESUMEN

Glioma is the most common malignant tumor in central nervous system, with significant health burdens to patients. Due to the intrinsic characteristics of glioma and the lack of breakthroughs in treatment modalities, the prognosis for most patients remains poor. This results in a heavy psychological and financial load worldwide. In recent years, cannabidiol (CBD) has garnered widespread attention and research due to its anti-tumoral, anti-inflammatory, and neuroprotective properties. This review comprehensively summarizes the preclinical and clinical research on the use of CBD in glioma therapy, as well as the current status of nanomedicine formulations of CBD, and discusses the potential and challenges of CBD in glioma therapy in the future.


Asunto(s)
Cannabidiol , Glioma , Cannabidiol/uso terapéutico , Cannabidiol/farmacología , Humanos , Glioma/tratamiento farmacológico , Glioma/patología , Animales , Investigación Biomédica Traslacional , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Nanomedicina/métodos
5.
Nanoscale ; 16(29): 13718-13754, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38954406

RESUMEN

Recently, nanotechnology has shown great potential in the field of cancer therapy due to its ability to improve the stability and solubility and reduce side effects of drugs. The biomimetic mineralization strategy based on natural proteins and metal ions provides an innovative approach for the synthesis of nanoparticles. This strategy utilizes the unique properties of natural proteins and the mineralization ability of metal ions to combine nanoparticles through biomimetic mineralization processes, achieving the effective treatment of tumors. The precise control of the mineralization process between proteins and metal ions makes it possible to obtain nanoparticles with the ideal size, shape, and surface characteristics, thereby enhancing their stability and targeting ability in vivo. Herein, initially, we analyze the role of protein molecules in biomineralization and comprehensively review the functions, properties, and applications of various common proteins and metal particles. Subsequently, we systematically review and summarize the application directions of nanoparticles synthesized based on protein biomineralization in tumor treatment. Specifically, we discuss their use as efficient drug delivery carriers and role in mediating monotherapy and synergistic therapy using multiple modes. Also, we specifically review the application of nanomedicine constructed through biomimetic mineralization strategies using natural proteins and metal ions in improving the efficiency of tumor immunotherapy.


Asunto(s)
Nanopartículas , Neoplasias , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Humanos , Nanopartículas/química , Nanopartículas/uso terapéutico , Animales , Proteínas/química , Proteínas/metabolismo , Materiales Biomiméticos/química , Portadores de Fármacos/química , Nanomedicina , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Biomineralización
6.
Artículo en Inglés | MEDLINE | ID: mdl-39044339

RESUMEN

Nanozymes are nanomaterials with intrinsic enzyme-like activity with selected advantages over native enzymes such as simple synthesis, controllable activity, high stability, and low cost. These materials have been explored as surrogates to natural enzymes in biosensing, therapeutics, environmental protection, and many other fields. Among different nanozymes classes, metal- and metal oxide-based nanozymes are the most widely studied. In recent years, bi- and tri-metallic nanomaterials have emerged often showing improved nanozyme activity, some of which even possess multifunctional enzyme-like activity. Taking this concept even further, high-entropy nanomaterials, that is, complex multicomponent alloys and ceramics like oxides, may potentially enhance activity even further. However, the addition of various elements to increase catalytic activity may come at the cost of increased toxicity. Since many nanozyme compositions are currently being explored for in vivo biomedical applications, such as cancer therapeutics, toxicity considerations in relation to nanozyme application in biomedicine are of vital importance for translation. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Diagnostic Tools > Diagnostic Nanodevices.


Asunto(s)
Nanoestructuras , Humanos , Animales , Nanoestructuras/química , Enzimas/química , Enzimas/metabolismo , Nanomedicina , Metales/química
7.
Int J Nanomedicine ; 19: 6857-6893, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39005956

RESUMEN

Periodontitis is a disease of inflammation that affects the tissues supporting the periodontium. It is triggered by an immunological reaction of the gums to plaque, which leads to the destruction of periodontal attachment structures. Periodontitis is one of the most commonly recognized dental disorders in the world and a major factor in the loss of adult teeth. Scaling and root planing remain crucial for managing patients with persistent periodontitis. Nevertheless, exclusive reliance on mechanical interventions like periodontal surgery, extractions, and root planning is insufficient to halt the progression of periodontitis. In response to the problem of bacterial resistance, some researchers are committed to finding alternative therapies to antibiotics. In addition, some scholars focus on finding new materials to provide a powerful microenvironment for periodontal tissue regeneration and promote osteogenic repair. Nanoparticles possess distinct therapeutic qualities, including exceptional antibacterial, anti-inflammatory, and antioxidant properties, immunomodulatory capacities, and the promotion of bone regeneration ability, which made them can be used for the treatment of periodontitis. However, there are many problems that limit the clinical translation of nanoparticles, such as toxic accumulation in cells, poor correlation between in vitro and in vivo, and poor animal-to-human transmissibility. In this paper, we review the present researches on nanoparticles in periodontitis treatment from the perspective of three main categories: inorganic nanoparticles, organic nanoparticles, and nanocomposites (including nanofibers, hydrogels, and membranes). The aim of this review is to provide a comprehensive and recent update on nanoparticles-based therapies for periodontitis. The conclusion section summarizes the opportunities and challenges in the design and clinical translation of nanoparticles for the treatment of periodontitis.


Asunto(s)
Nanopartículas , Periodontitis , Humanos , Periodontitis/terapia , Periodontitis/tratamiento farmacológico , Nanopartículas/química , Animales , Antibacterianos/química , Antibacterianos/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Nanocompuestos/química , Nanocompuestos/uso terapéutico , Nanomedicina/métodos
8.
Int J Nanomedicine ; 19: 6757-6776, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38983132

RESUMEN

Glioma is a primary malignant tumor in the central nervous system. In recent years, the treatment of glioma has developed rapidly, but the overall survival of glioma patients has not significantly improved. Due to the presence of the blood-brain barrier and intracranial tumor barrier, many drugs with good effects to cure glioma in vitro cannot be accurately transported to the corresponding lesions. In order to enable anti-tumor drugs to overcome the barriers and target glioma, nanodrug delivery systems have emerged recently. It is gratifying that liposomes, as a multifunctional nanodrug delivery carrier, which can be compatible with hydrophilic and hydrophobic drugs, easily functionalized by various targeted ligands, biodegradable, and hypoimmunogenic in vivo, has become a quality choice to solve the intractable problem of glioma medication. Therefore, we focused on the liposome nanodrug delivery system, and summarized its current research progress in glioma. Hopefully, this review may provide new ideas for the research and development of liposome-based nanomaterials for the clinical treatment of glioma.


Asunto(s)
Antineoplásicos , Barrera Hematoencefálica , Neoplasias Encefálicas , Glioma , Liposomas , Nanoestructuras , Glioma/tratamiento farmacológico , Liposomas/química , Humanos , Neoplasias Encefálicas/tratamiento farmacológico , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Animales , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Nanomedicina/métodos , Portadores de Fármacos/química
9.
Int J Nanomedicine ; 19: 7383-7398, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39050878

RESUMEN

Tumor vessels characterized by abnormal functions and structures hinder the infiltration and immune antigen presentation of immune cells by inducing the formation of an immunosuppressive microenvironment ("cold" environment). Vascular-targeted therapy has been proven to enhance immune stimulation and the effectiveness of immunotherapy by modulating the "cold" microenvironment, such as hypoxia and an acidic microenvironment. Notably, a therapeutic strategy based on "vascular-immune" crosstalk can achieve dual regulation of tumor vessels and the immune system by reprogramming the tumor microenvironment (TME), thus forming a positive feedback loop between tumor vessels and the immune microenvironment. From this perspective, we discuss the factors of tumor angiogenesis and "cold" TME formation. Building on this foundation, some vascular-targeted therapeutic drugs will be elaborated upon in detail to achieve dual regulation of tumor vessels and immunity. More importantly, we focus on cutting-edge nanotechnology in view of "vascular-immune" crosstalk and discuss the rational fabrication of tailor-made nanosystems for efficiently enhancing immunotherapy.


Asunto(s)
Inmunoterapia , Neoplasias , Neovascularización Patológica , Microambiente Tumoral , Humanos , Neoplasias/terapia , Neoplasias/inmunología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Inmunoterapia/métodos , Neovascularización Patológica/inmunología , Neovascularización Patológica/terapia , Animales , Sistema de Administración de Fármacos con Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Nanomedicina , Nanopartículas/química
10.
Int J Nanomedicine ; 19: 6499-6513, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38946887

RESUMEN

Purpose: To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the heterogeneous distribution of radiation sensitizers. Materials and Methods: In this work, a novel nanomedicine, designated as PLGA@IR780-Bi-DTPA (PIBD), was engineered by loading the radiation sensitizer Bi-DTPA and the photothermal agent IR780 onto poly(lactic-co-glycolic acid) (PLGA). This design leverages the tumor-targeting ability of IR780 to ensure selective accumulation of the nanoparticles in tumor cells, particularly within the mitochondria. The effect of the photothermal therapy-enhanced radiation therapy was also examined to assess the alleviation of hypoxia and the enhancement of radiation sensitivity. Results: The PIBD nanoparticles exhibited strong capacity in mitochondrial targeting and selective tumor accumulation. Upon activation by 808 nm laser irradiation, the nanoparticles effectively alleviated local hypoxia by photothermal effect enhanced blood supplying to improve oxygen content, thereby enhancing the ROS production for effective RT. Comparative studies revealed that PIBD-induced RT significantly outperformed conventional RT in treating hypoxic tumors. Conclusion: This design of tumor-targeting photothermal therapy-enhanced radiation therapy nanomedicine would advance the development of targeted drug delivery system for effective RT regardless of hypoxic microenvironment.


Asunto(s)
Nanopartículas , Terapia Fototérmica , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Especies Reactivas de Oxígeno , Animales , Terapia Fototérmica/métodos , Especies Reactivas de Oxígeno/metabolismo , Nanopartículas/química , Línea Celular Tumoral , Humanos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Ratones , Indoles/farmacología , Indoles/química , Hipoxia Tumoral/efectos de los fármacos , Hipoxia Tumoral/efectos de la radiación , Fármacos Sensibilizantes a Radiaciones/farmacología , Fármacos Sensibilizantes a Radiaciones/química , Ratones Endogámicos BALB C , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neoplasias/radioterapia , Neoplasias/terapia , Neoplasias/metabolismo , Nanomedicina
11.
Int J Nanomedicine ; 19: 6619-6641, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38975321

RESUMEN

The high malignant degree and poor prognosis of pancreatic cancer (PC) pose severe challenges to the basic research and clinical translation of next-generation therapies. The rise of immunotherapy has improved the treatment of a variety of solid tumors, while the application in PC is highly restricted by the challenge of immunosuppressive tumor microenvironment. The latest progress of nanotechnology as drug delivery platform and immune adjuvant has improved drug delivery in a variety of disease backgrounds and enhanced tumor therapy based on immunotherapy. Based on the immune loop of PC and the status quo of clinical immunotherapy of tumors, this article discussed and critically analyzed the key transformation difficulties of immunotherapy adaptation to the treatment of PC, and then proposed the rational design strategies of new nanocarriers for drug delivery and immune regulation, especially the design of combined immunotherapy. This review also put forward prospective views on future research directions, so as to provide information for the new means of clinical treatment of PC combined with the next generation of nanotechnology and immunotherapy.


Asunto(s)
Inmunoterapia , Neoplasias Pancreáticas , Microambiente Tumoral , Humanos , Inmunoterapia/métodos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/inmunología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Animales , Nanotecnología/métodos , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Nanopartículas/uso terapéutico , Nanomedicina/métodos
12.
Theranostics ; 14(9): 3486-3508, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38948064

RESUMEN

Rationale: Device implantation frequently triggers cardiac remodeling and fibrosis, with monocyte-driven inflammatory responses precipitating arrhythmias. This study investigates the role of m6A modification enzymes METTL3 and METTL14 in these responses and explores a novel therapeutic strategy targeting these modifications to mitigate cardiac remodeling and fibrosis. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from patients with ventricular septal defects (VSD) who developed conduction blocks post-occluder implantation. The expression of METTL3 and METTL14 in PBMCs was measured. METTL3 and METTL14 deficiencies were induced to evaluate their effect on angiotensin II (Ang II)-induced myocardial inflammation and fibrosis. m6A modifications were analyzed using methylated RNA immunoprecipitation followed by quantitative PCR. NF-κB pathway activity and levels of monocyte migration and fibrogenesis markers (CXCR2 and TGF-ß1) were assessed. An erythrocyte microvesicle-based nanomedicine delivery system was developed to target activated monocytes, utilizing the METTL3 inhibitor STM2457. Cardiac function was evaluated via echocardiography. Results: Significant upregulation of METTL3 and METTL14 was observed in PBMCs from patients with VSD occluder implantation-associated persistent conduction block. Deficiencies in METTL3 and METTL14 significantly reduced Ang II-induced myocardial inflammation and fibrosis by decreasing m6A modification on MyD88 and TGF-ß1 mRNAs. This disruption reduced NF-κB pathway activation, lowered CXCR2 and TGF-ß1 levels, attenuated monocyte migration and fibrogenesis, and alleviated cardiac remodeling. The erythrocyte microvesicle-based nanomedicine delivery system effectively targeted inflamed cardiac tissue, reducing inflammation and fibrosis and improving cardiac function. Conclusion: Inhibiting METTL3 and METTL14 in monocytes disrupts the NF-κB feedback loop, decreases monocyte migration and fibrogenesis, and improves cardiac function. Targeting m6A modifications of monocytes with STM2457, delivered via erythrocyte microvesicles, reduces inflammation and fibrosis, offering a promising therapeutic strategy for cardiac remodeling associated with device implantation.


Asunto(s)
Fibrosis , Metiltransferasas , Monocitos , FN-kappa B , Humanos , Metiltransferasas/metabolismo , Metiltransferasas/genética , Monocitos/metabolismo , Masculino , Animales , FN-kappa B/metabolismo , Eritrocitos/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Femenino , Metilación , Ratones , Factor de Crecimiento Transformador beta1/metabolismo , Micropartículas Derivadas de Células/metabolismo , Leucocitos Mononucleares/metabolismo , Angiotensina II/metabolismo , Receptores de Interleucina-8B/metabolismo , Receptores de Interleucina-8B/genética , Remodelación Ventricular , Miocardio/metabolismo , Miocardio/patología , Nanomedicina/métodos
13.
Nanotheranostics ; 8(4): 473-496, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38961885

RESUMEN

Cardiotoxicity, the often-overlooked second leading cause of death in cancer patients, has been associated with certain anticancer drugs. These drugs can induce cardiac damage through various pathways, and their adverse effects on the heart are not fully understood. Cardiotoxicity is a major issue in cancer treatment, particularly with chemotherapeutics, because it can cause cardiac dysfunction such as hypotension, heart failure, and even death. Doxorubicin, 5-fluorouracil, and trastuzumab, all of which are very potent anticancer drugs, are known to cause cardiotoxicity. When it comes to lowering cardiotoxicity and alleviating the harmful effects of chemotherapy medications, nanomedicine has the potential to transport therapeutic molecules. Nanotheranostics offers novel options for identifying and treating cardiotoxicity resulting from a wide range of substances, including anticancer medications. Additionally, theranostics platforms such as micellar systems, carbon-based nanomedicine, solid lipid nanoparticles, polymeric nanoparticles, and liposomes can transport chemotherapeutic medications while minimising their cardiotoxicity. The present level of understanding of the molecular and cellular processes that lead to cardiotoxicity in reaction to both traditional chemotherapy and targeted drug delivery systems is summarised in this article. This review delves into nanomedicine and nanotheranostics, with an emphasis on reducing anticancer medication-induced cardiac toxicity. Nanotheranostics provide potential solutions for early diagnosis and tailored therapy of heart injury by combining diagnostic and therapeutic capabilities into nanomedicine.


Asunto(s)
Antineoplásicos , Cardiotoxicidad , Nanomedicina , Nanomedicina Teranóstica , Humanos , Antineoplásicos/efectos adversos , Antineoplásicos/química , Cardiotoxicidad/etiología , Nanomedicina/métodos , Nanomedicina Teranóstica/métodos , Animales , Cardiopatías/inducido químicamente , Neoplasias/tratamiento farmacológico , Nanopartículas/química
14.
Artículo en Inglés | MEDLINE | ID: mdl-38955512

RESUMEN

Enzyme-based therapy has garnered significant attention for its current applications in various diseases. Despite the notable advantages associated with the use of enzymes as therapeutic agents, that could have high selectivity, affinity, and specificity for the target, their application faces challenges linked to physico-chemical and pharmacological properties. These limitations can be addressed through the encapsulation of enzymes in nanoplatforms as a comprehensive solution to mitigate their degradation, loss of activity, off-target accumulation, and immunogenicity, thus enhancing bioavailability, therapeutic efficacy, and circulation time, thereby reducing the number of administrations, and ameliorating patient compliance. The exploration of novel nanomedicine-based enzyme therapeutics for the treatment of challenging diseases stands as a paramount goal in the contemporary scientific landscape, but even then it is often not enough. Combining an enzyme with another therapeutic (e.g., a small molecule, another enzyme or protein, a monoclonal antibody, or a nucleic acid) within a single nanocarrier provides innovative multidrug-integrated therapy and ensures that both the actives arrive at the target site and exert their therapeutic effect, leading to synergistic action and superior therapeutic efficacy. Moreover, this strategic approach could be extended to gene therapy, a field that nowadays has gained increasing attention, as enzymes acting at genomic level and nucleic acids may be combined for synergistic therapy. This multicomponent therapeutic approach opens opportunities for promising future developments. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.


Asunto(s)
Terapia Enzimática , Nanomedicina , Humanos , Animales
15.
Molecules ; 29(11)2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38893460

RESUMEN

There is a myriad of diseases that plague the world ranging from infectious, cancer and other chronic diseases with varying interventions. However, the dynamism of causative agents of infectious diseases and incessant mutations accompanying other forms of chronic diseases like cancer, have worsened the treatment outcomes. These factors often lead to treatment failure via different drug resistance mechanisms. More so, the cost of developing newer drugs is huge. This underscores the need for a paradigm shift in the drug delivery approach in order to achieve desired treatment outcomes. There is intensified research in nanomedicine, which has shown promises in improving the therapeutic outcome of drugs at preclinical stages with increased efficacy and reduced toxicity. Regardless of the huge benefits of nanotechnology in drug delivery, challenges such as regulatory approval, scalability, cost implication and potential toxicity must be addressed via streamlining of regulatory hurdles and increased research funding. In conclusion, the idea of nanotechnology in drug delivery holds immense promise for optimizing therapeutic outcomes. This work presents opportunities to revolutionize treatment strategies, providing expert opinions on translating the huge amount of research in nanomedicine into clinical benefits for patients with resistant infections and cancer.


Asunto(s)
Sistemas de Liberación de Medicamentos , Nanomedicina , Nanoestructuras , Humanos , Nanoestructuras/química , Nanomedicina/métodos , Neoplasias/tratamiento farmacológico , Animales , Nanotecnología/métodos
16.
Int J Nanomedicine ; 19: 4893-4906, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38828202

RESUMEN

Introduction: The tumor microenvironment (TME) has attracted considerable attention as a potential therapeutic target for cancer. High levels of reactive oxygen species (ROS) in the TME may act as a stimulus for drug release. In this study, we have developed ROS-responsive hyaluronic acid-bilirubin nanoparticles (HABN) loaded with doxorubicin (DOX@HABN) for the specific delivery and release of DOX in tumor tissue. The hyaluronic acid shell of the nanoparticles acts as an active targeting ligand that can specifically bind to CD44-overexpressing tumors. The bilirubin core has intrinsic anti-cancer activity and ROS-responsive solubility change properties. Methods & Results: DOX@HABN showed the HA shell-mediated targeting ability, ROS-responsive disruption leading to ROS-mediated drug release, and synergistic anti-cancer activity against ROS-overproducing CD44-overexpressing HeLa cells. Additionally, intravenously administered HABN-Cy5.5 showed remarkable tumor-targeting ability in HeLa tumor-bearing mice with limited distribution in major organs. Finally, intravenous injection of DOX@HABN into HeLa tumor-bearing mice showed synergistic anti-tumor efficacy without noticeable side effects. Conclusion: These findings suggest that DOX@HABN has significant potential as a cancer-targeting and TME ROS-responsive nanomedicine for targeted cancer treatment.


Asunto(s)
Bilirrubina , Doxorrubicina , Receptores de Hialuranos , Ácido Hialurónico , Nanomedicina , Nanopartículas , Especies Reactivas de Oxígeno , Microambiente Tumoral , Ácido Hialurónico/química , Microambiente Tumoral/efectos de los fármacos , Animales , Especies Reactivas de Oxígeno/metabolismo , Humanos , Doxorrubicina/farmacología , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/administración & dosificación , Nanopartículas/química , Ratones , Células HeLa , Receptores de Hialuranos/metabolismo , Bilirrubina/química , Bilirrubina/farmacología , Bilirrubina/farmacocinética , Liberación de Fármacos , Ratones Endogámicos BALB C , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/administración & dosificación , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo
17.
Int J Nanomedicine ; 19: 4857-4875, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38828195

RESUMEN

Brain diseases are the most devastating problem among the world's increasingly aging population, and the number of patients with neurological diseases is expected to increase in the future. Although methods for delivering drugs to the brain have advanced significantly, none of these approaches provide satisfactory results for the treatment of brain diseases. This remains a challenge due to the unique anatomy and physiology of the brain, including tight regulation and limited access of substances across the blood-brain barrier. Nanoparticles are considered an ideal drug delivery system to hard-to-reach organs such as the brain. The development of new drugs and new nanomaterial-based brain treatments has opened various opportunities for scientists to develop brain-specific delivery systems that could improve treatment outcomes for patients with brain disorders such as Alzheimer's disease, Parkinson's disease, stroke and brain tumors. In this review, we discuss noteworthy literature that examines recent developments in brain-targeted nanomedicines used in the treatment of neurological diseases.


Asunto(s)
Barrera Hematoencefálica , Encéfalo , Sistemas de Liberación de Medicamentos , Nanomedicina , Humanos , Nanomedicina/métodos , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Encéfalo/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Animales , Nanopartículas/química , Encefalopatías/tratamiento farmacológico , Sistema de Administración de Fármacos con Nanopartículas/química , Sistema de Administración de Fármacos con Nanopartículas/farmacocinética , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Alzheimer/tratamiento farmacológico
18.
Acta Biomater ; 183: 306-317, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38838902

RESUMEN

Advanced hepatocellular carcinoma (HCC) is one of the most challenging cancers because of its heterogeneous and aggressive nature, precluding the use of curative treatments. Sorafenib (SOR) is the first approved molecular targeting agent against the mitogen-activated protein kinase (MAPK) pathway for the noncurative therapy of advanced HCC; yet, any clinically meaningful benefits from the treatment remain modest, and are accompanied by significant side effects. Here, we hypothesized that using a nanomedicine platform to co-deliver SOR with another molecular targeting drug, metformin (MET), could tackle these issues. A micelle self-assembled with amphiphilic polypeptide methoxy poly(ethylene glycol)-block-poly(L-phenylalanine-co-l-glutamic acid) (mPEG-b-P(LP-co-LG)) (PM) was therefore designed for combinational delivery of two molecular targeted drugs, SOR and MET, to hepatomas. Compared with free drugs, the proposed, dual drug-loaded micelle (PM/SOR+MET) enhanced the drugs' half-life in the bloodstream and drug accumulation at the tumor site, thereby inhibiting tumor growth effectively in the preclinical subcutaneous, orthotopic and patient-derived xenograft hepatoma models without causing significant systemic and organ toxicity. Collectively, these findings demonstrate an effective dual-targeting nanomedicine strategy for treating advanced HCC, which may have a translational potential for cancer therapeutics. STATEMENT OF SIGNIFICANCE: Treatment of advanced hepatocellular carcinoma (HCC) remains a formidable challenge due to its aggressive nature and the limitations inherent to current therapies. Despite advancements in molecular targeted therapies, such as Sorafenib (SOR), their modest clinical benefits coupled with significant adverse effects underscore the urgent need for more efficacious and less toxic treatment modalities. Our research presents a new nanomedicine platform that synergistically combines SOR with metformin within a specialized diblock polypeptide micelle, aiming to enhance therapeutic efficacy while reducing systemic toxicity. This innovative approach not only exhibits marked antitumor efficacy across multiple HCC models but also significantly reduces the toxicity associated with current treatments. Our dual-molecular targeting approach unveils a promising nanomedicine strategy for the molecular treatment of advanced HCC, potentially offering more effective and safer treatment alternatives with significant translational potential.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Micelas , Nanomedicina , Sorafenib , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Animales , Humanos , Sorafenib/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Metformina/farmacología , Terapia Molecular Dirigida , Ratones Desnudos , Ratones , Sinergismo Farmacológico , Línea Celular Tumoral , Polietilenglicoles/química , Ensayos Antitumor por Modelo de Xenoinjerto , Antineoplásicos/farmacología , Antineoplásicos/química , Ratones Endogámicos BALB C
19.
EBioMedicine ; 105: 105200, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38876044

RESUMEN

Nanoparticles have shown great potential for tumor targeting delivery via enhanced permeability and retention effect. However, the tumor mechanical microenvironment, characterized by dense extracellular matrix (ECM), high tumor stiffness and solid stress, leads to only 0.7% of administered dose accumulating in solid tumors and even fewer (∼0.0014%) reaching tumor cells, limiting the therapeutic efficacy of nanoparticles. Furthermore, the tumor mechanical microenvironment can regulate tumor cell stemness, promote tumor invasion, metastasis and reduce treatment efficacy. In this review, methods detecting the mechanical are introduced. Strategies for modulating the mechanical microenvironment including elimination of dense ECM by physical, chemical and biological methods, disruption of ECM formation, depletion or inhibition of cancer-associated fibroblasts, are then summarized. Finally, prospects and challenges for further clinical applications of mechano-modulating strategies to enhance the therapeutic efficacy of nanomedicines are discussed. This review may provide guidance for the rational design and application of nanoparticles in clinical settings.


Asunto(s)
Antineoplásicos , Matriz Extracelular , Nanopartículas , Neoplasias , Microambiente Tumoral , Humanos , Microambiente Tumoral/efectos de los fármacos , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Matriz Extracelular/metabolismo , Animales , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Sistemas de Liberación de Medicamentos , Nanomedicina/métodos
20.
Int J Pharm ; 660: 124345, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-38885775

RESUMEN

Advancements in nanotechnology were vastly applied in medicine and pharmacy, especially in the field of nano-delivery systems. It took a long time for these systems to ensure precise delivery of very delicate molecules, such as RNA, to cells at concentrations that yield remarkable efficiency, with success rates reaching 95.0% and 94.5%. These days, there are several advantages of using nanotechnological solutions in the prevention and treatment of cancer and viral infections. Its interventions improve treatment outcomes both due to increased effectiveness of the drug at target location and by reducing adverse reactions, thereby increasing patient adherence to the therapy. Based on the current knowledge an updated review was made, and perspective, opportunities and challenges in nanomedicine were discussed. The methods employed include comprehensive examination of existing literature and studies on nanoparticles and nano-delivery systems including both in vitro tests performed on cell cultures and in vivo assessments carried out on appropriate animal models, with a specific emphasis on their applications in oncology and virology. This brings together various aspects including both structure and formation as well as its association with characteristic behaviour in organisms, providing a novel perspective. Furthermore, the practical application of these systems in medicine and pharmacy with a focus on viral diseases and malignancies was explored. This review can serve as a valuable guide for fellow researchers, helping them navigate the abundance of findings in this field. The results indicate that applications of nanotechnological solutions for the delivery of medicinal products improving therapeutic outcomes will continue to expand.


Asunto(s)
Sistemas de Liberación de Medicamentos , Nanomedicina , Nanotecnología , Neoplasias , Virosis , Humanos , Animales , Neoplasias/tratamiento farmacológico , Virosis/tratamiento farmacológico , Nanotecnología/métodos , Sistemas de Liberación de Medicamentos/métodos , Nanomedicina/métodos , Nanopartículas , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antivirales/administración & dosificación , Antivirales/química
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