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1.
Int J Nanomedicine ; 14: 4187-4209, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31289440

RESUMO

Circulating tumor cells (CTCs) are disseminated cancer cells. The occurrence and circulation of CTCs seem key for metastasis, still the major cause of cancer-associated deaths. As such, CTCs are investigated as predictive biomarkers. However, due to their rarity and heterogeneous biology, CTCs' practical use has not made it into the clinical routine. Clearly, methods for the effective isolation and reliable detection of CTCs are urgently needed. With the development of nanotechnology, various nanosystems for CTC isolation and enrichment and CTC-targeted cancer therapy have been designed. Here, we summarize the relationship between CTCs and tumor metastasis, and describe CTCs' unique properties hampering their effective enrichment. We comment on nanotechnology-based systems for CTC isolation and recent achievements in microfluidics and lab-on-a-chip technologies. We discuss recent advances in CTC-targeted cancer therapy exploiting the unique properties of nanomaterials. We conclude by introducing developments in CTC-directed nanosystems and other advanced technologies currently in (pre)clinical research.


Assuntos
Biomarcadores Tumorais/análise , Separação Celular/métodos , Nanomedicina/métodos , Células Neoplásicas Circulantes/patologia , Biomarcadores Tumorais/isolamento & purificação , Materiais Biomiméticos , Grafite , Humanos , Dispositivos Lab-On-A-Chip , Microfluídica/instrumentação , Microfluídica/métodos , Nanoestruturas/química , Nanotecnologia/métodos , Nanotubos de Carbono
2.
Biomater Sci ; 7(9): 3581-3593, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265011

RESUMO

Nanomedicine has shown remarkable progress in preclinical studies of tumor treatment. Over the past decade, scientists have developed various nanocarriers (NCs) for delivering drugs into the tumor area. However, the average amount of accumulated drugs in tumor sites is far from satisfactory. This limitation is strongly related to the corona formation during blood circulation. To overcome this issue, NCs should be designed to become highly stealthy by modifying their surface charge. However, at the same time, stealthy effects not only prevent protein formation but also alleviate the cellular uptake of NCs. Therefore, it is necessary to develop NCs with switchable properties, which are stealthy in the circulation system and sticky when arriving at tumor sites. In this review, we discuss the recent strategies to develop passive and active charge-switchable NCs, known as chameleon-like drug delivery systems, which can reversibly transform their surface from stealthy to sticky and have various designs.


Assuntos
Antineoplásicos/administração & dosagem , Nanocápsulas/química , Animais , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Nanomedicina/métodos , Tamanho da Partícula , Permeabilidade , Polímeros/química , Propriedades de Superfície
3.
Int J Mol Sci ; 20(9)2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31035335

RESUMO

The purpose of this paper was to outline the development of short peptide targeting of the human prostate specific antigen (hPSA), and to evaluate its effectiveness in staining PSA in human prostate cancer tissue. The targeting of the hPSA antigen by means of antisense peptide AVRDKVG was designed according to a three-step method involving: 1. The selection of the molecular target (hPSA epitope), 2. the modeling of an antisense peptide (paratope) based on the epitope sequence, and 3. the spectroscopic evaluation of sense-antisense peptide binding. We then modified standard hPSA immunohistochemical staining practice by using a biotinylated antisense peptide instead of the standard monoclonal antibody and compared the results of both procedures. Immunochemical testing on human tissue showed the applicability of the antisense peptide technology to human molecular targets. This methodology represents a new approach to deriving peptide ligands and potential lead compounds for the development of novel diagnostic substances, biopharmaceuticals and vaccines.


Assuntos
Biomarcadores Tumorais/imunologia , Peptídeos/imunologia , Antígeno Prostático Específico/imunologia , Neoplasias da Próstata/imunologia , Humanos , Imuno-Histoquímica , Masculino , Nanomedicina/métodos , Estrutura Secundária de Proteína
4.
Int J Nanomedicine ; 14: 2301-2325, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31114188

RESUMO

Antimicrobial agents have been widely investigated for protecting against microbial infections in modern health. Drug-related limitations, poor bioavailability, toxicity to mammalian cells, and frequent bacteria drug resistance are major challenges faced when exploited in nanomedicine forms. Specific attention has been paid to control nanomaterial-based infection against numerous challenging pathogens in addition to improved drug delivery, targeting, and pharmacokinetic (PK) profiles, and thus, efficient antimicrobials have been fabricated using diverse components (metals, metal oxides, synthetic and semisynthetic polymers, natural or biodegradable polymers, etc). The present review covers several nanocarriers delivered through various routes of administration, highlighting major findings to control microbial infection as compared to using the free drug. Results over the past decade support the consistent development of various nanomedicines capable of improving biological significance and therapeutic benefits against an array of microbial strains. Depending on the intended application of nanomedicine, infection control will be challenged by various factors such as weighing the risk-benefits in healthcare settings, nanomaterial-induced (eco)toxicological hazards, frequent development of antibiotic resistance, scarcity of in vivo toxicity data, and a poor understanding of microbial interactions with nanomedicine at the molecular level. This review summarizes well-established informative data for nanomaterials used for infection control and safety concerns of nanomedicines to healthcare sectors followed by the significance of a unique "safe-by-design" approach.


Assuntos
Controle de Infecções , Nanomedicina/métodos , Animais , Anti-Infecciosos/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Nanoestruturas/química , Nanoestruturas/ultraestrutura
5.
Artif Cells Nanomed Biotechnol ; 47(1): 1674-1692, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31066300

RESUMO

Cisplatin cis-(diammine)dichloridoplatinum(II) (CDDP) is the first platinum-based complex approved by the food and drug administration (FDA) of the United States (US). Cisplatin is the first line chemotherapeutic agent used alone or combined with radiations or other anti-cancer agents for a broad range of cancers such as lung, head and neck. Aroplatin™, Lipoplatin™ and SPI-077 are PEGylated liposome-based nano-formulations that are still under clinical trials. They have many limitations, for example, poor aqueous solubility, drug resistance and toxicities, which can be overcome by encapsulating the cisplatin in Nemours nanocarriers. The extensive literature from different electronic databases covers the different nano-delivery systems that are developed for cisplatin. This review critically emphasizes on the recent advancement, development, innovations and updated literature reported for different carrier systems for CDDP.


Assuntos
Cisplatino/química , Portadores de Fármacos/química , Nanomedicina/métodos , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Animais , Cisplatino/uso terapêutico , Humanos
6.
Nat Commun ; 10(1): 2150, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31089130

RESUMO

Peptide-major histocompatibility complex class II (pMHCII)-based nanomedicines displaying tissue-specific autoantigenic epitopes can blunt specific autoimmune conditions by re-programming cognate antigen-experienced CD4+ T-cells into disease-suppressing T-regulatory type 1 (TR1) cells. Here, we show that single pMHCII-based nanomedicines displaying epitopes from mitochondrial, endoplasmic reticulum or cytoplasmic antigens associated with primary biliary cholangitis (PBC) or autoimmune hepatitis (AIH) can broadly blunt PBC, AIH and Primary Sclerosing Cholangitis in various murine models in an organ- rather than disease-specific manner, without suppressing general or local immunity against infection or metastatic tumors. Therapeutic activity is associated with cognate TR1 cell formation and expansion, TR1 cell recruitment to the liver and draining lymph nodes, local B-regulatory cell formation and profound suppression of the pro-inflammatory capacity of liver and liver-proximal myeloid dendritic cells and Kupffer cells. Thus, autoreactivity against liver-enriched autoantigens in liver autoimmunity is not disease-specific and can be harnessed to treat various liver autoimmune diseases broadly.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Antígenos de Histocompatibilidade Classe II/imunologia , Hepatopatias/tratamento farmacológico , Nanopartículas/administração & dosagem , Peptídeos/administração & dosagem , Idoso , Animais , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Linhagem Celular , Modelos Animais de Doenças , Epitopos/imunologia , Feminino , Antígenos de Histocompatibilidade Classe II/química , Humanos , Fígado/efeitos dos fármacos , Fígado/imunologia , Hepatopatias/imunologia , Masculino , Camundongos , Pessoa de Meia-Idade , Nanomedicina/métodos , Nanopartículas/química , Peptídeos/química , Peptídeos/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia
7.
Medicina (Kaunas) ; 55(4)2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31013662

RESUMO

: Background and objectives: Previous studies have shown anti-tumor activity of quercetin (QT). However, the low bioavailability of QT has restricted its use. This study aimed to assess the toxic effect of QT encapsulated in solid lipid nanoparticles (QT-SLNs) on the growth of MCF-7 human breast cancer cells. Materials and Methods: MCF-7 and MCF-10A (non-tumorigenic cell line) cell lines treated with 25 µmol/mL of QT or QT-SLNs for 48 h. Cell viability, colony formation, oxidative stress, and apoptosis were evaluated to determine the toxic effects of the QT-SLNs. Results: The QT-SLNs with appropriate characteristics (particle size of 85.5 nm, a zeta potential of -22.5 and encapsulation efficiency of 97.6%) were prepared. The QT-SLNs showed sustained QT release until 48 h. Cytotoxicity assessments indicated that QT-SLNs inhibited MCF-7 cells growth with a low IC50 (50% inhibitory concentration) value, compared to the free QT. QT-SLNs induced a significant decrease in the viability and proliferation of MCF-7 cells, compared to the free QT. QT-SLN significantly increased reactive oxygen species (ROS) level and MDA contents and significantly decreased antioxidant enzyme activity in the MCF-7 cells. Following QT-SLNs treatment, the expression of the Bcl-2 protein significantly decreased, whereas Bx expression showed a significant increase in comparison with free QT-treated cells. Furthermore, The QT-SLNs significantly increased apoptotic and necrotic indexes in MCF-7 cells. Viability, proliferation, oxidative stress and apoptosis of MCF-10A cells were not affected by QT or QT-SLNs. Conclusion: According to the results of this study, SLN significantly enhanced the toxic effect of QT against human breast cancer cells.


Assuntos
Antioxidantes/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Nanocápsulas , Nanomedicina/métodos , Quercetina/uso terapêutico , Apoptose/efeitos dos fármacos , Catalase/análise , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Malondialdeído/análise , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Espécies Reativas de Oxigênio/análise , Superóxido Dismutase/análise , Resultado do Tratamento
8.
Artif Cells Nanomed Biotechnol ; 47(1): 997-1013, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30945957

RESUMO

It is only in the last 20 years that many of the original ideas on artificial cells are being increasingly applied and extended by researchers around the world. Artificial cell has now evolved into nanomedicine, biotherapeutics, blood substitutes, drug delivery, enzyme/gene therapy, cancer therapy, cell/stem cell therapy, nanoparticles, liposomes, bioencapsulation, replicating synthetic cells, cell encapsulation/scaffold, biosorbent/immunosorbent haemoperfusion/plasmapheresis, regenerative medicine, encapsulated microbe, nanobiotechnology, nanotechnology and other areas. More futuristic research includes nanorobot, nanocomputer, multimodal locomotion delivery robot and others. This review starts with a general overview followed by specific examples in more details.


Assuntos
Células Artificiais , Terapia Enzimática/métodos , Hemoperfusão/métodos , Nanomedicina/métodos , Neoplasias/terapia , Plasmaferese/métodos , Medicina Regenerativa/métodos , Animais , Biotecnologia , Substitutos Sanguíneos , Cápsulas , Humanos , Imunoadsorventes , Lipossomos , Microbiologia , Nanopartículas , Neoplasias/genética , Transplante de Células-Tronco
9.
J Nanobiotechnology ; 17(1): 52, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30971278

RESUMO

BACKGROUND: Currently, the main goal of cancer research is to increase longevity of patients suffering malignant cancers. The promising results of BCc1 in vitro and vivo experiments made us look into the effect of BCc1 nanomedicine on patients with cancer in a clinical trial. METHODS: The present investigation was a randomized, double-blind, placebo-controlled, parallel, and multicenter study in which 123 patients (30-to-85-year-old men and women) with metastatic and non-metastatic gastric cancer, in two separate groups of BCc1 nanomedicine or placebo, were selected using a permuted block randomization method. For metastatic and non-metastatic patients, a daily dose of 3000 and 1500 mg was prescribed, respectively. Overall survival (OS) as the primary endpoint and quality of life (measured using QLQ-STO22) and adverse effects as the secondary endpoints were studied. RESULTS: In metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (174 days [95% confidence interval (CI) 82.37-265.62]) than in placebo (62 days [95% CI 0-153.42]); hazard ratio (HR): 0.5 [95% CI 0.25-0.98; p = 0.046]. In non-metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (529 days [95% CI 393.245-664.75]) than in placebo (345 days [95% CI 134.85-555.14]); HR: 0.324 [95% CI 0.97-1.07; p = 0.066]. The QLQ-STO22 assessment showed a mean difference improvement of 3.25 and 2.29 (p value > 0.05) in BCc1 nanomedicine and a mean difference deterioration of - 4.42 and - 3 (p-value < 0.05) in placebo with metastatic and non-metastatic patients, respectively. No adverse effects were observed. CONCLUSION: The findings of this trial has provided evidence for the potential capacity of BCc1 nanomedicine for treatment of cancer. Trial registration IRCTID, IRCT2017101935423N1. Registered on 19 October 2017, http://www.irct.ir/ IRCT2017101935423N1.


Assuntos
Adenocarcinoma/terapia , Nanocompostos/química , Neoplasias Gástricas/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nanomedicina/métodos , Metástase Neoplásica , Manejo da Dor , Modelos de Riscos Proporcionais , Qualidade de Vida , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do Tratamento
10.
AAPS PharmSciTech ; 20(4): 160, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30968269

RESUMO

Over the last several decades, nanoparticulate delivery systems have emerged as advanced drug and gene delivery tools for cancer therapy. However, their translation into clinical use still poses major challenges. Even though many innovative nanoparticulate approaches have shown very positive results both in vitro and in vivo, few of them have found a place in clinical practice. Possible factors responsible for the existing gap in the translation of nanomedicine to clinical practice may include oversimplification of enhanced permeability and retention effect, lack of correlation between the in vivo animal data vs their translation in human, and challenging multiple biological steps experienced during systemic delivery of nanomedicine. Understanding these challenges and coming up with solutions to overcome them is an important step in effective translation of nanomedicine into clinical practice. This review focuses on advancements in the field of nanomedicine used for anti-cancer therapy, including passive targeting, active targeting, and stimuli-controlled delivery. The review further reveals some of the challenges that are currently faced by pharmaceutical scientists in translation of nanomedicine; these include lack of adequate models for preclinical testing that can predict efficacy in humans, absence of appropriate regulatory guidelines for their approval processes, and difficulty in scale-up of the manufacturing of nanodrug delivery systems. A better understanding of these challenges will help us in filling the gap between the bench and bedside in cancer therapy.


Assuntos
Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Nanomedicina , Neoplasias/terapia , Animais , Humanos , Nanomedicina/métodos
11.
Phys Med ; 60: 7-13, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31000089

RESUMO

Gold nanoparticles (GNPs) are an emerging area of interest in radiation therapy due to their unique radio-sensitizing properties. In the literature, the enhancing capability of GNPs is usually quantified using the metric dose enhancement ratio (DER). Traditionally, the focus of the vast majority of studies has always been on intravenous administration of GNPs. However, recent work showed the potential of using GNP inhalation, rather than intravenous injection, to enhance the dose to the lung. Yet, some of these studies are employing simplistic analytical methods to calculate DER and, thus far, there are no detailed computations of the enhancement profiles therein. Moreover, the coating on the GNP surface can be adversely affected by the large gradient of the radiation dose in the immediate vicinity of GNPs, leading to the rupture of ligands and detachment of GNPs from the surface of the membrane, and hence the loss of its efficacy. In this study, a next-generation deterministic code was used to resolve the DER profile at the interface between the septum, air, and surface of GNPs when they are attached and detached. The results show that the large values of DER in conjunction with the developed hot spots are very effective in lung treatment; on the other hand, coating rupture can lead to significant reduction in DER that may reach 64%. Thus, GNPs can be beneficial in inhalational medicine to treat lung cancer, provided that more comprehensive studies on the characteristics of the coating are addressed to maximize the radio-therapeutic benefit of GNPs.


Assuntos
Compostos de Ouro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Radiossensibilizantes/administração & dosagem , Administração por Inalação , Simulação por Computador , Sistemas de Liberação de Medicamentos/efeitos adversos , Elétrons , Estudos de Viabilidade , Compostos de Ouro/efeitos adversos , Compostos de Ouro/química , Humanos , Neoplasias Pulmonares/radioterapia , Nanopartículas Metálicas/efeitos adversos , Nanopartículas Metálicas/química , Modelos Teóricos , Nanomedicina/métodos , Radiossensibilizantes/efeitos adversos , Radiossensibilizantes/química , Radioterapia/métodos , Raios X
12.
Nat Commun ; 10(1): 1690, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30979901

RESUMO

The effect of direct or indirect binding of intercalant molecules on DNA structure is of fundamental importance in understanding the biological functioning of DNA. Here we report on self-suspended DNA nanobundles as ultrasensitive nanomechanical resonators for structural studies of DNA-ligand complexes. Such vibrating nanostructures represent the smallest mechanical resonator entirely composed of DNA. A correlative analysis between the mechanical and structural properties is exploited to study the intrinsic changes of double strand DNA, when interacting with different intercalant molecules (YOYO-1 and GelRed) and a chemotherapeutic drug (Cisplatin), at different concentrations. Possible implications of our findings are related to the study of interaction mechanism of a wide category of molecules with DNA, and to further applications in medicine, such as optimal titration of chemotherapeutic drugs and environmental studies for the detection of heavy metals in human serum.


Assuntos
DNA/química , Substâncias Intercalantes/química , Ligantes , Nanomedicina/métodos , Antineoplásicos/química , Cisplatino/química , Cristalografia por Raios X , Microscopia Eletrônica de Varredura , Microscopia de Fluorescência , Simulação de Dinâmica Molecular , Neoplasias/tratamento farmacológico , Ligação Proteica , Estresse Mecânico
13.
Prog Brain Res ; 245: 145-200, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30961867

RESUMO

Alzheimer's disease (AD) is estimated to be afflicting over 55 millions of individual worldwide in 2018-19 for which no suitable clinical therapeutic measures have been developed so far. Thus, there is an urgent need to explore novel therapeutic strategies using nanodelivery of drugs and agents either alone or in combination for superior neuroprotection in AD and enhanced quality of life of the affected individuals. There are reports that AD is often associated with diminished neurotrophic factors and neprilysin together with enhancement of phosphorylated Tau (p-Tau) within the brain and in the cerebrospinal fluid (CSF). Thus, studies aiming to enhance neurotrophic factors and neprilysin together with neutralizing p-Tau within the central nervous system (CNS) may alleviate brain pathology in AD. In this review these strategies are discussed using nanotechnological approaches largely based on our own investigations in relation to current literature in the field.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Aminoácidos/administração & dosagem , Anticorpos/administração & dosagem , Nanomedicina/métodos , Nanofios/uso terapêutico , Neprilisina/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Proteínas tau/imunologia , Animais , Humanos
14.
Prog Brain Res ; 245: 201-246, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30961868

RESUMO

Parkinson's disease (PD) is affecting >10 million people worldwide for which no suitable cure has been developed so far. Roughly, about two people per thousand populations are affected with PD like symptoms especially over the age of 50. About 1% of the populations above 60 years suffer from PD-like disease. The prevalence of the disease is increasing over the years, and future projections by 2020 could be 12-14 millions people affected by the disease. Thus, exploration of suitable therapeutic measures is the need of the hour to enhance quality of the life of PD patients. PD induced brain pathology includes loss of dopaminergic neurons in the substantia niagra that could later extends to other cortical regions causing loss of voluntary motor control. Deposition of α-synuclein in the brain further leads to neurodegeneration. However, the exact cause of PD is still unknown. It appears that breakdown of the blood-brain barrier (BBB) and leakage of serum component into the brain could lead to neurodegeneration in PD. Thus, novel treatment strategies that are able to restore BBB breakdown and enhance neuronal plasticity and neuroregeneration in PD could be effective in future therapy. With the advancement of nanotechnology, it is worthwhile to understand the role of nanodelivery of selected agents in PD to enhance neuroprotection. In this review new role of BBB, brain edema, and neuropathology in PD is discussed. In addition, superior neuroprotection induced by nanowired delivery of a multimodal drug cerebrolysin in PD is summarized based on our own investigations.


Assuntos
Aminoácidos/farmacologia , Nanomedicina/métodos , Nanofios/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Aminoácidos/administração & dosagem , Animais , Humanos , Fármacos Neuroprotetores/administração & dosagem , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia
15.
Prog Brain Res ; 245: 263-279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30961870

RESUMO

Parkinson's disease (PD) as a motor disorder is pathologically featured by the loss of dopaminergic neurons of the substantia nigra compacta (SNc) and the consequent depletion of dopamine in the striatum. However, motor signs are detectable when the loss of dopaminergic striatal terminals exceeds to the dopaminergic neuronal degeneration in SN. Hence, recent evidences about the topological organization of the nigrostriatal system could provide novel insights about the progression of the neurodegenerative process as well as the correct application of the novel therapeutic strategies. Though dopaminergic drugs and different routes of administration have been proposed to treat PD, most of the effects are symptomatic with temporary effects resorting to invasive procedures to ameliorate the side effects. Since the blood-brain barrier (BBB) is the main obstacle for most of molecules to access to the brain, ongoing research is focused on halting the progression of PD through the use of those technologies that allow the effective delivery and diffusion of therapeutic molecules to the central nervous system for bypassing BBB and avoiding the side effects. In this context, nanotechnology is emerging as a promising tool for drug delivery. In fact, nanodelivery of restorative treatments in PD, such as gene therapy increased the effectiveness of neurotrophic factors for restoring the dopamine deficit and improving motor deficit in rodent models. Therefore, the present review is focused on the description and identification of the available nanotherapies developed in experimental models of PD which could suppose an important advance for controlled delivery of nanobioactive components into the brain and one more step for the clinical projection.


Assuntos
Antioxidantes/administração & dosagem , Barreira Hematoencefálica , Dopaminérgicos/administração & dosagem , Nanomedicina/métodos , Fatores de Crescimento Neural/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Animais , Humanos
16.
Prog Brain Res ; 245: 57-88, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30961872

RESUMO

The treatment of Alzheimer's disease (AD) is up to today one of the most unsuccessful examples of biomedical science. Despite the high number of literature evidences detailing the multifactorial and complex etiopathology of AD, no cure is yet present on the market and the available treatments are only symptomatic. The reasons could be ascribed on two main factors: (i) lack of ability of the majority of drugs to cross the blood-brain barrier (BBB), thus excluding the brain for any successful therapy; (ii) lack of selectivity and specificity of drugs, decreasing the efficacy of even potent anti-AD drugs. The exploitation of specifically engineered nanomedicines planned to cross the BBB and to target the most "hot" site of action (i.e., ß-amyloid) is one of the most interesting innovations in drug delivery and could reasonably represent an promising choice for possible treatments and even early-diagnosis of AD. In this chapter, we therefore outline the most talented approaches in AD treatment with a specific focus on the main advantages/drawbacks and future possible translation to clinic application.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/efeitos dos fármacos , Barreira Hematoencefálica , Nanomedicina/métodos , Fármacos Neuroprotetores/administração & dosagem , Nootrópicos/administração & dosagem , Animais , Humanos
17.
Prog Brain Res ; 245: 89-118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30961873

RESUMO

Concussive head injury (CHI) is quite prevalent in military personnel leading to lifetime disability in more than 85% of cases. Other reasons of CHI include motor vehicle accident, fall or blunt trauma under various conditions. In United States of America (USA) alone more than 150k cases of head injury are added every year for which no suitable therapeutic strategies are still available. Thus, there is a need to expand our knowledge in treating CHI cases with novel therapeutic measures to enhance the quality of life of head injury victims. With recent advancements in nanodelivery of drugs for superior neuroprotective effects in neurological diseases, our laboratory is engaged in understanding the role of nanowired delivery of suitable drugs in treating CHI and other neurodegenerative diseases. DL-3-n-butylphthalide (NBP) is an extract of Chinese celery and is able to induce profound neuroprotection following ischemic stroke and other related neurological dysfunction. Thus, it is quite likely that synthetic NBP could have pronounced neuroprotective effects in CHI as well. We believe that nanodelivery of NBP have superior neuroprotection in CHI. In this review neuroprotective effects of nanowired delivery of NBP in CHI induced brain pathology is described. Our experimental observations show that nanowired delivery of NBP results in superior neuroprotection than the regular NBP in CHI. The probable mechanisms and functional significance of our finding in relation to military medicine is discussed based on our own investigations.


Assuntos
Benzofuranos/administração & dosagem , Concussão Encefálica/tratamento farmacológico , Edema Encefálico/tratamento farmacológico , Nanomedicina/métodos , Nanofios/uso terapêutico , Fármacos Neuroprotetores/administração & dosagem , Animais , Concussão Encefálica/complicações , Concussão Encefálica/patologia , Edema Encefálico/etiologia , Edema Encefálico/patologia , Humanos
18.
Nat Commun ; 10(1): 1821, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015519

RESUMO

Self-powered implantable medical electronic devices that harvest biomechanical energy from cardiac motion, respiratory movement and blood flow are part of a paradigm shift that is on the horizon. Here, we demonstrate a fully implanted symbiotic pacemaker based on an implantable triboelectric nanogenerator, which achieves energy harvesting and storage as well as cardiac pacing on a large-animal scale. The symbiotic pacemaker successfully corrects sinus arrhythmia and prevents deterioration. The open circuit voltage of an implantable triboelectric nanogenerator reaches up to 65.2 V. The energy harvested from each cardiac motion cycle is 0.495 µJ, which is higher than the required endocardial pacing threshold energy (0.377 µJ). Implantable triboelectric nanogenerators for implantable medical devices offer advantages of excellent output performance, high power density, and good durability, and are expected to find application in fields of treatment and diagnosis as in vivo symbiotic bioelectronics.


Assuntos
Arritmia Sinusal/cirurgia , Fenômenos Eletrofisiológicos , Coração/fisiologia , Nanomedicina/instrumentação , Marca-Passo Artificial , Animais , Arritmia Sinusal/etiologia , Procedimentos Cirúrgicos Cardíacos/instrumentação , Procedimentos Cirúrgicos Cardíacos/métodos , Linhagem Celular , Dimetilpolisiloxanos/química , Modelos Animais de Doenças , Desenho de Equipamento , Masculino , Camundongos , Nanomedicina/métodos , Nylons/química , Politetrafluoretileno/química , Implantação de Prótese/instrumentação , Implantação de Prótese/métodos , Sus scrofa
19.
Pharm Res ; 36(6): 78, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30945009

RESUMO

This review article presents the state-of-the-art in the major imaging modalities supplying relevant information on patient health by real-time monitoring to establish an accurate diagnosis and potential treatment plan. We draw a comprehensive comparison between all imagers and ultimately end with our focus on two main types of scanners: X-ray CT and MRI scanners. Numerous types of imaging probes for both imaging techniques are described, as well as reviewing their strengths and limitations, thereby showing the current need for the development of new diagnostic contrast agents (CAs). The role of nanoparticles in the design of CAs is then extensively detailed, reviewed and discussed. We show how nanoparticulate agents should be promising alternatives to molecular ones and how they are already paving new routes in the field of nanomedicine.


Assuntos
Meios de Contraste , Diagnóstico por Imagem/métodos , Diagnóstico por Imagem/tendências , Nanomedicina/métodos , Animais , Meios de Contraste/efeitos adversos , Meios de Contraste/química , Diagnóstico por Imagem/instrumentação , Sistemas de Liberação de Medicamentos , Humanos , Estrutura Molecular , Nanomedicina/tendências , Nanopartículas/efeitos adversos , Nanopartículas/química , Tamanho da Partícula , Polímeros/química , Propriedades de Superfície
20.
Nat Commun ; 10(1): 1704, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30979885

RESUMO

Cancer cells exhibit slightly elevated levels of reactive oxygen species (ROS) compared with normal cells, and approximately 90% of intracellular ROS is produced in mitochondria. In situ mitochondrial ROS amplification is a promising strategy to enhance cancer therapy. Here we report cancer cell and mitochondria dual-targeting polyprodrug nanoreactors (DT-PNs) covalently tethered with a high content of repeating camptothecin (CPT) units, which release initial free CPT in the presence of endogenous mitochondrial ROS (mtROS). The in situ released CPT acts as a cellular respiration inhibitor, inducing mtROS upregulation, thus achieving subsequent self-circulation of CPT release and mtROS burst. This mtROS amplification endows long-term high oxidative stress to induce cancer cell apoptosis. This current strategy of endogenously activated mtROS amplification for enhanced chemodynamic therapy overcomes the short lifespan and action range of ROS, avoids the penetration limitation of exogenous light in photodynamic therapy, and is promising for theranostics.


Assuntos
Antineoplásicos/química , Liberação Controlada de Fármacos , Mitocôndrias/metabolismo , Pró-Fármacos , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose , Camptotecina/química , Linhagem Celular Tumoral , Feminino , Citometria de Fluxo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Nanomedicina/métodos , Nanotecnologia , Neoplasias/metabolismo , Estresse Oxidativo , Fotoquimioterapia
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