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1.
Nanomaterials (Basel) ; 11(10)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34685134

RESUMO

In this study, we demonstrate the visible-light-assisted photoelectrochemical (PEC) biosensing of uric acid (UA) by using graphene oxide nanoribbons (GONRs) as PEC electrode materials. Specifically, GONRs with controlled properties were synthesized by the microwave-assisted exfoliation of multi-walled carbon nanotubes. For the detection of UA, GONRs were adopted to modify either a screen-printed carbon electrode (SPCE) or a glassy carbon electrode (GCE). Cyclic voltammetry analyses indicated that all Faradaic currents of UA oxidation on GONRs with different unzipping/exfoliating levels on SPCE increased by more than 20.0% under AM 1.5 irradiation. Among these, the GONRs synthesized under a microwave power of 200 W, namely GONR(200 W), exhibited the highest increase in Faradaic current. Notably, the GONR(200 W)/GCE electrodes revealed a remarkable elevation (~40.0%) of the Faradaic current when irradiated by light-emitting diode (LED) light sources under an intensity of illumination of 80 mW/cm2. Therefore, it is believed that our GONRs hold great potential for developing a novel platform for PEC biosensing.

2.
Mater Sci Eng C Mater Biol Appl ; 128: 112311, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474862

RESUMO

Herein, we design a rGO-based magnetic nanocomposite by decorating rGO with citrate-coated magnetic nanoparticles (CMNP). The magnetic rGO (mrGO) was modified by phospholipid-polyethylene glycol to prepare PEGylated mrGO, for conjugating with gastrin-releasing peptide receptor (GRPR)-binding peptide (mrGOG). The anticancer drug doxorubicin (DOX) was bound to mrGO (mrGOG) by π-π stacking for drug delivery triggered by the low pH value in the endosome. The mrGOG showed enhanced photothermal effect under NIR irradiation, endorsing its role for dual targeted DOX delivery. With efficient DOX release in the endosomal environment and heat generation from light absorption in the NIR range, mrGOG/DOX could be used for combination chemo-photothermal therapy after intracellular uptake by cancer cells. We characterized the physico-chemical as well as biological properties of the synthesized nanocomposites. The mrGOG is stable in biological buffer solution, showing high biocompatibility and minimum hemolytic properties. Using U87 glioblastoma cells, we confirmed the magnetic drug targeting effect in vitro for selective cancer cell killing. The peptide ligand-mediated targeted delivery increases the efficiency of intracellular uptake of both nanocomposite and DOX up to ~3 times due to the over-expressed GRPR on U87 surface, leading to higher cytotoxicity. The increased cytotoxicity using mrGOG over mrGO was shown from a decreased IC50 value (0.70 to 0.48 µg/mL) and an increased cell apoptosis rate (19.8% to 47.1%). The IC50 and apoptosis rate changed further to 0.19 µg/mL and 76.8% in combination with NIR laser irradiation, with the photothermal effect supported from upregulation of heat shock protein HSP70 expression. Using U87 tumor xenograft model created in nude mice, we demonstrated that magnetic guidance after intravenous delivery of mrGOG/DOX could significantly reduce tumor size and prolong animal survival over free DOX and non-magnetic guided groups. Augmented with NIR laser treatment for 5 min, the anti-cancer efficacy significantly improves with elevated cell apoptosis and reduced cell proliferation. Together with safety profiles from hematological as well as major organ histological analysis of treated animals, the mrGOG nanocomposite is an effective nanomaterial for combination chemo-photothermal cancer therapy.


Assuntos
Hipertermia Induzida , Nanocompostos , Neoplasias , Animais , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Grafite , Fenômenos Magnéticos , Camundongos , Camundongos Nus , Fototerapia , Receptores da Bombesina
3.
Cancers (Basel) ; 13(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34359590

RESUMO

As a hydrophobic photosensitizer, IR-780 suffers from poor water solubility and low photostability under near infrared (NIR) light, which severely limits its use during successive NIR laser-assisted photothermal/photodynamic therapy (PTT/PDT). To solve this problem, we fabricate cationic IR-780-loaded liposomes (ILs) by entrapping IR-780 within the lipid bilayer of liposomes. We demonstrate enhanced photostability of IR-780 in ILs with well-preserved photothermal response after three repeated NIR laser exposures, in contrast to the rapid decomposition of free IR-780. The cationic nature of ILs promotes fast endocytosis of liposomal IR-780 by U87MG human glioblastoma cells within 30 min. For PTT/PDT in vitro, ILs treatment plus NIR laser irradiation leads to overexpression of heat shock protein 70 and generation of intracellular reactive oxygen species by U87MG cells, resulting in enhanced cytotoxicity and higher cell apoptosis rate. Using intracranial glioma xenograft in nude mice and administration of ILs by convection enhanced delivery (CED) to overcome blood-brain barrier, liposomal IR-780 could be specifically delivered to the brain tumor, as demonstrated from fluorescence imaging. By providing a highly stable liposomal IR-780, ILs significantly improved anti-cancer efficacy in glioma treatment, as revealed from various diagnostic imaging tools and histological examination. Overall, CED of ILs plus successive laser-assisted PTT/PDT may be an alternative approach for treating brain tumor, which can retard glioma growth and prolong animal survival times from orthotopic brain tumor models.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34415720

RESUMO

The low vessel density and oxygen concentration in hypoxia are the main causes of reduced efficiency of anticancer therapeutics and can stimulate the tumor's relapse. Research showed that macrophages could cross the blood-vessel barriers and reach the hypoxic regions of tumors. Using macrophages in a drug delivery system has been a promising method for tumor targeting in recent years. In this work, we successfully modified monocyte chemoattractant protein-1 (MCP-1) and iron-based metal-organic framework (MIL-100(Fe)) on the photothermal agent, gold nanorods (GNRs) (i.e., MCP-1/GNR@MIL-100(Fe)), to increase cellular uptake and biocompatibility. The results of TEM, UV-vis, and FTIR all confirmed that we'd synthesized MCP-1/GNR@MIL-100(Fe) successfully, and the MCP-1/GNR@MIL-100(Fe) also showed good biocompatibility. A transwell migration assay illustrated that our material attracted macrophages, and the material uptake amount was increased by 1.5 times after MCP-1 functionalization. It also indicated that the macrophages have a tumor-targeting ability. In the in vivo experiment, we subcutaneously implanted U251 MG cells in nude mice as a xenograft model to demonstrate the photothermal activity of MCP-1/GNR@MIL-100(Fe). With successive NIR treatment, the tumor growth could be controlled, and the tumor volume still remained below 100 mm3 after laser treatment. MCP-1/GNR@MIL-100(Fe) combined with the laser treatment showed an excellent antitumor efficacy from the histology of tumor tissues, survival rates, and bioluminescence imaging.

5.
J Vis Exp ; (173)2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34398149

RESUMO

A 2D monocular endoscope has been used in transcanal transpromontory vestibular schwannoma surgery instead of craniotomy. However, the absence of depth perception is the limitation of this approach. With the loss of depth perception, the surgeon will be not able to perform delicate and particularly complicated surgery. A binocular endoscope has been developed to provide stereoscopic vision with better depth perception for complicated anatomic structures and has been applied in some endoscopic surgeries. However, the diameter of the endoscope is a limitation in the performance of transcanal otologic surgeries. A small diameter endoscope facilitates easier surgery in a restricted space. A computer-based 3D imaging system can obtain 3D images in real-time using a small monocular endoscope. In this study, to evaluate the feasibility of a computer-based 3D imaging system for endoscopic lateral skull base surgery, we applied this 3D imaging system in a transcanal transpromontorial approach in two patients with vestibular schwannomas. The surgical procedure was completed without complication in these two cases. There was no mortality, perioperative complications, nor notable postoperative complications. Using this computer-based 3D imaging system, a better depth perception and stereoscopic vision was observed compared to a conventional 2D endoscope. The improvement in depth perception offers superior management of the complicated surgical anatomy.


Assuntos
Neuroma Acústico , Computadores , Endoscópios , Endoscopia , Humanos , Imageamento Tridimensional , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/cirurgia
6.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804239

RESUMO

Cancer is one of the deadliest diseases in human history with extremely poor prognosis. Although many traditional therapeutic modalities-such as surgery, chemotherapy, and radiation therapy-have proved to be successful in inhibiting the growth of tumor cells, their side effects may vastly limited the actual benefits and patient acceptance. In this context, a nanomedicine approach for cancer therapy using functionalized nanomaterial has been gaining ground recently. Considering the ability to carry various anticancer drugs and to act as a photothermal agent, the use of carbon-based nanomaterials for cancer therapy has advanced rapidly. Within those nanomaterials, reduced graphene oxide (rGO), a graphene family 2D carbon nanomaterial, emerged as a good candidate for cancer photothermal therapy due to its excellent photothermal conversion in the near infrared range, large specific surface area for drug loading, as well as functional groups for functionalization with molecules such as photosensitizers, siRNA, ligands, etc. By unique design, multifunctional nanosystems could be designed based on rGO, which are endowed with promising temperature/pH-dependent drug/gene delivery abilities for multimodal cancer therapy. This could be further augmented by additional advantages offered by functionalized rGO, such as high biocompatibility, targeted delivery, and enhanced photothermal effects. Herewith, we first provide an overview of the most effective reducing agents for rGO synthesis via chemical reduction. This was followed by in-depth review of application of functionalized rGO in different cancer treatment modalities such as chemotherapy, photothermal therapy and/or photodynamic therapy, gene therapy, chemotherapy/phototherapy, and photothermal/immunotherapy.


Assuntos
Grafite/uso terapêutico , Nanomedicina/tendências , Nanoestruturas/uso terapêutico , Neoplasias/terapia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Grafite/química , Humanos , Nanoestruturas/química , Neoplasias/patologia , Fotoquimioterapia/métodos , Fototerapia/métodos
7.
Biomaterials ; 272: 120765, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33780686

RESUMO

Ischemic stroke, and the consequent brain cell death, is a common cause of death and disability worldwide. Current treatments that primarily aim to relieve symptoms are relatively inefficient in achieving brain tissue regeneration and functional recovery, and thus novel therapeutic options are urgently needed. Although cell-based therapies have shown promise for treating the infarcted brain, a recurring challenge is the inadequate retention and engraftment of transplanted cells at the target tissue, thereby limiting the ultimate therapeutic efficacy. Here, we show that transplantation of preassembled three-dimensional (3D) spheroids of mesenchymal stem cells (MSCs) and vascular endothelial cells (ECs) results in significantly improved cell retention and survival compared with conventional mixed-cell suspensions. The transplanted 3D spheroids exhibit notable neuroprotective, proneurogenic, proangiogenic and anti-scarring potential as evidenced by clear extracellular matrix structure formation and paracrine factor expression and secretion; this ultimately results in increased structural and motor function recovery in the brain of an ischemic stroke mouse model. Therefore, transplantation of MSCs and ECs using the 3D cell spheroid configuration not only reduces cell loss during cell harvesting/administration but also enhances the resultant therapeutic benefit, thus providing important proof-of-concept for future clinical translation.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , AVC Isquêmico , Transplante de Células-Tronco Mesenquimais , Acidente Vascular Cerebral , Animais , Isquemia Encefálica/terapia , Células Endoteliais , Camundongos , Esferoides Celulares , Acidente Vascular Cerebral/terapia
8.
Cancers (Basel) ; 12(11)2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33142721

RESUMO

The consistent expression of disialoganglioside GD2 in neuroblastoma tumor cells and its restricted expression in normal tissues open the possibility to use it for molecularly targeted neuroblastoma therapy. On the other hand, immunoliposomes combining antibody-mediated tumor recognition with liposomal delivery of chemotherapeutics have been proved to enhance therapeutic efficacy in brain tumors. Therefore, we develop immunoliposomes (ImmuLipCP) conjugated with anti-GD2 antibody, for targeted co-delivery of CPT-11 and panobinostat in this study. U87MG human glioma cell line and its drug resistant variant (U87DR), which were confirmed to be associated with low and high expression of cell surface GD2, were employed to compare the targeting efficacy. From in vitro cytotoxicity assay, CPT-11 showed synergism drug interaction with panobinostat to support co-delivery of both drugs with ImmuLipCP for targeted synergistic combination chemotherapy. The molecular targeting mechanism was elucidated from intracellular uptake efficacy by confocal microscopy and flow cytometry analysis, where 6-fold increase in liposome and 1.8-fold increase in drug uptake efficiency was found using targeted liposomes. This enhanced intracellular trafficking for drug delivery endows ImmuLipCP with pronounced cytotoxicity toward U87DR cells in vitro, with 1.6-fold increase of apoptosis rate. Using xenograft nude mice model with subcutaneously implanted U87DR cells, we observe similar biodistribution profile but 5.1 times higher accumulation rate of ImmuLip from in vivo imaging system (IVIS) observation of Cy5.5-labelled liposomes. Taking advantage of this highly efficient GD-2 targeting, ImmuLipCP was demonstrated to be an effective cancer treatment modality to significantly enhance the anti-cancer therapeutic efficacy in U87DR tumors, shown from the significant reduced tumor size in and prolonged survival time of experiment animals as well as diminished expression of cell proliferation and enhanced expression of apoptosis marker proteins in tumor section.

9.
ACS Omega ; 5(45): 29342-29350, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33225165

RESUMO

Neurosurgical procedures often cause damage to the brain tissue at the periphery from surgical manipulations. Especially during retraction, a large amount of pressure could be applied on the brain surface, which can damage it, leading to brain herniation, which can be fatal for patients. To resolve this issue, we have developed a pressure sensor that can be used to monitor the applied pressure during surgery for intraoperative care. This device was tested on a rodent model to create a superficial surgically induced damage profile for three different applied pressures (30, 50, and 70 mmHg) and compared to a standard intracranial pressure monitoring system. Magnetic resonance imaging has been performed after surgical procedures to detect the herniation caused by applied pressure. To evaluate the damage to brain cells and tissue rupture, histological analysis was performed using hematoxylin and eosin staining. A scoring system was developed to understand the severity of the surgically induced brain injury, which will help neurosurgeons to limit the pressure to an optimum point without causing damage.

10.
Int J Nanomedicine ; 15: 7569-7582, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116488

RESUMO

Introduction: Nasopharyngeal carcinoma (NPC) is a common cancer in southern China and Taiwan, and radiation therapy combined with or without chemotherapy is its mainstay treatment. Although it is highly sensitive to radiotherapy, local recurrence and distant metastasis remain difficult unsolved problems. In recent years, graphene oxide (GO) has been found to be a promising novel anticancer drug carrier. Here, we present our designed functionalized GO, polyethylene glycol-coated GO (GO-PEG), as a drug carrier, which was loaded with erlotinib and showed promising anticancer effects on NPC cells. Methods: The effects of GO-PEG-erlotinib on the proliferation, migration, and invasion of NPC cells were investigated by WST-8 assay, wound healing assay, and invasion assay, respectively. RNA sequencing was conducted and analyzed to determine the molecular mechanisms by which GO-PEG-erlotinib affects NPC cells. Results: Our results showed that GO-PEG-erlotinib reduced NPC cell viability in a dose-dependent manner and also inhibited the migration and invasion of NPC cells. The RNA sequencing revealed several related molecular mechanisms. Conclusion: GO-PEG-erlotinib effectively suppressed NPC cell proliferation, migration, and invasion, likely by several mechanisms. GO-PEG-erlotinib may be a potential therapeutic agent for treating NPC in the future.


Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos/química , Cloridrato de Erlotinib/administração & dosagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Cloridrato de Erlotinib/farmacocinética , Cloridrato de Erlotinib/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Grafite/química , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Polietilenoglicóis/química
11.
Int J Mol Sci ; 21(19)2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32993166

RESUMO

In this study, we aimed to develop a multifunctional drug/gene delivery system for the treatment of glioblastoma multiforme by combining the ligand-mediated active targeting and the pH-triggered drug release features of graphene oxide (GO). Toward this end, we load irinotecan (CPT-11) to cetuximab (CET)-conjugated GO (GO-CET/CPT11) for pH-responsive drug release after endocytosis by epidermal growth factor receptor (EGFR) over-expressed U87 human glioblastoma cells. The ultimate injectable drug/gene delivery system was designed by co-entrapping stomatin-like protein 2 (SLP2) short hairpin RNA (shRNA) and GO-CET/CPT11 in thermosensitive chitosan-g-poly(N-isopropylacrylamide) (CPN) polymer solution, which offers a hydrogel depot for localized, sustained delivery of the therapeutics after the in situ formation of CPN@GO-CET/CPT11@shRNA hydrogel. An optimal drug formulation was achieved by considering both the loading efficiency and loading content of CPT-11 on GO-CET. A sustained and controlled release behavior was found for CPT-11 and shRNA from CPN hydrogel. Confocal microscopy analysis confirmed the intracellular trafficking for the targeted delivery of CPT-11 through interactions of CET with EGFR on the U87 cell surface. The efficient transfection of U87 using SLP2 shRNA was achieved using CPN as a delivery milieu, possibly by the formation of shRNA/CPN polyplex after hydrogel degradation. In vitro cell culture experiments confirmed cell apoptosis induced by CPT-11 released from acid organelles in the cytoplasm by flow cytometry, as well as reduced SLP2 protein expression and inhibited cell migration due to gene silencing. Finally, in vivo therapeutic efficacy was demonstrated using the xenograft of U87 tumor-bearing nude mice through non-invasive intratumoral delivery of CPN@GO-CET/CPT11@shRNA by injection. Overall, we have demonstrated the novelty of this thermosensitive hydrogel to be an excellent depot for the co-delivery of anticancer drugs and siRNA. The in situ forming hydrogel will not only provide extended drug release but also combine the advantages offered by the chitosan-based copolymer structure for siRNA delivery to broaden treatment modalities in cancer therapy.


Assuntos
Proteínas Sanguíneas , Quitosana , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Glioblastoma , Grafite , Irinotecano , Proteínas de Membrana , Proteínas de Neoplasias , RNA Interferente Pequeno , Proteínas Sanguíneas/antagonistas & inibidores , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismo , Linhagem Celular Tumoral , Quitosana/química , Quitosana/farmacologia , Receptores ErbB/agonistas , Receptores ErbB/genética , Receptores ErbB/metabolismo , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/terapia , Grafite/química , Grafite/farmacologia , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Irinotecano/química , Irinotecano/farmacologia , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia
12.
ACS Appl Mater Interfaces ; 12(36): 40141-40152, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32845120

RESUMO

Understanding the molecular mechanisms of graphene oxide (GO)-based biomaterials is important for logical biomedical applications. Previous studies have revealed biointeractions between GO and immune effector cells, but the effects on neutrophils, crucial cells in the immune system, have not been thoroughly discussed. In this study, GO nanoformulations were synthesized with different functional groups, including GO, GO-carboxylated (GO-COOH), and PEGylated GO (GO-PEG), with different surface features, which were elucidated using imaging methods and surface-sensitive quantitative spectroscopic techniques, including atomic force microscopy (AFM), transmission electron microscopy (TEM), and X-ray photoemission spectroscopy (XPS). The GO-based nanoformulations elicited reactive oxygen species (ROS) generation and neutrophil extracellular trap (NET) formation in human neutrophils. Nanoformulated GO stimulates NET development via the formation of ROS. An endocytosis study revealed that nanoformulated GO facilitated internalization by neutrophils via macropinocytosis and actin-dependent phagocytosis. Importantly, calcium mobilization and phosphorylation proteins such as mitogen-activated protein kinases (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38) and AKT were involved in the activation of neutrophils. These findings offer the first verification that nanoformulated GO exhibits direct effects on human neutrophils.


Assuntos
Materiais Biocompatíveis/farmacologia , Grafite/farmacologia , Nanopartículas/química , Neutrófilos/efeitos dos fármacos , Adulto , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Antígeno CD11b/biossíntese , Grafite/síntese química , Grafite/química , Humanos , Ativação de Neutrófilo/efeitos dos fármacos , Ativação de Neutrófilo/imunologia , Neutrófilos/imunologia , Tamanho da Partícula , Espécies Reativas de Oxigênio/imunologia , Propriedades de Superfície , Adulto Jovem
13.
Int J Mol Sci ; 21(15)2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32707876

RESUMO

In this work, we aimed to develop liposomal nanocomposites containing citric-acid-coated iron oxide magnetic nanoparticles (CMNPs) for dual magneto-photothermal cancer therapy induced by alternating magnetic field (AMF) and near-infrared (NIR) lasers. Toward this end, CMNPs were encapsulated in cationic liposomes to form nano-sized magnetic liposomes (MLs) for simultaneous magnetic hyperthermia (MH) in the presence of AMF and photothermia (PT) induced by NIR laser exposure, which amplified the heating efficiency for dual-mode cancer cell killing and tumor therapy. Since the heating capability is directly related to the amount of entrapped CMNPs in MLs, while the liposome size is important to allow internalization by cancer cells, response surface methodology was utilized to optimize the preparation of MLs by simultaneously maximizing the encapsulation efficiency (EE) of CMNPs in MLs and minimizing the size of MLs. The experimental design was performed based on the central composite rotatable design. The accuracy of the model was verified from the validation experiments, providing a simple and effective method for fabricating the best MLs, with an EE of 87% and liposome size of 121 nm. The CMNPs and the optimized MLs were fully characterized from chemical and physical perspectives. In the presence of dual AMF and NIR laser treatment, a suspension of MLs demonstrated amplified heat generation from dual hyperthermia (MH)-photothermia (PT) in comparison with single MH or PT. In vitro cell culture experiments confirmed the efficient cellular uptake of the MLs from confocal laser scanning microscopy due to passive accumulation in human glioblastoma U87 cells originated from the cationic nature of MLs. The inducible thermal effects mediated by MLs after endocytosis also led to enhanced cytotoxicity and cumulative cell death of cancer cells in the presence of AMF-NIR lasers. This functional nanocomposite will be a potential candidate for bimodal MH-PT dual magneto-photothermal cancer therapy.


Assuntos
Glioblastoma/tratamento farmacológico , Hipertermia Induzida/métodos , Lipossomos/química , Nanopartículas de Magnetita/química , Nanocompostos/química , Fototerapia/métodos , Células 3T3 , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Ácido Cítrico/química , Endocitose/efeitos dos fármacos , Glioblastoma/radioterapia , Humanos , Hipertermia , Hipertermia Induzida/instrumentação , Lasers , Lipossomos/síntese química , Lipossomos/ultraestrutura , Campos Magnéticos , Nanopartículas de Magnetita/efeitos da radiação , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Microscopia Eletrônica de Transmissão , Nanocompostos/efeitos da radiação , Tamanho da Partícula
14.
Diagnostics (Basel) ; 10(5)2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32365918

RESUMO

The diagnosis of Alzheimer's disease (AD) is frequently missed or delayed in clinical practice. To remedy this situation, we developed a screening, paper-based (P-ELISA) platform to detect ß-amyloid peptide 1-42 (Aß42) and provide rapid results using a small volume, easily accessible plasma sample instead of cerebrospinal fluid. The protocol outlined herein only requires 3 µL of sample per well and a short operating time (i.e., only 90 min). The detection limit of Aß42 is 63.04 pg/mL in a buffer system. This P-ELISA-based approach can be used for early, preclinical stage AD screening, including screening for amnestic mild cognitive impairment (MCI) due to AD. It may also be used for treatment and stage monitoring purposes. The implementation of this approach may provide tremendous impact for an afflicted population and may well prompt additional and expanded efforts in both academic and commercial communities.

15.
Appl Neuropsychol Adult ; : 1-10, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32301346

RESUMO

Conventional treatment for treating primary central nervous system lymphoma (PCNSL) has consisted of either whole-brain radiotherapy (WBRT) or methotrexate (MTX)-based combined modality therapy. However, delayed cognitive sequelae have emerged as a significant debilitating complication in PCNSL patients. A prospective observational case-series study with prospective assessments of neurocognitive functions (NCFs), neuroimaging, and activities of daily living in newly-diagnosed PCNSL patients was undertaken. A battery of neuropsychological measures, used to evaluate NCFs, is composed of ten standardized NCF tests, representing four domains sensitive to disease and treatment effects (executive function, attention, verbal memory, psychomotor speed), and activities of daily living. A total of 15 patients with newly-diagnosed PCNSL were consecutively enrolled in this study. Comparing the NCF scores between the baseline (before WBRT) and post-treatment (after combined chemoradiation therapy) intervals (Mean = 122.33 days, SD = 34.49, range = 77-196), neurobehavioral outcomes consistently remained improving or stable in almost each domain of NCF. Specifically, the scores on Paced Auditory Serial Addition Test-Revised (PASAT-R) were significantly improved between the baseline and post-chemoradiation assessment. Under the multidisciplinary treatment guidelines for treating patients with newly-diagnosed PCNSL, multi-domain NCF become stabilized and even improved after the course of conformal WBRT combined with or without MTX-based chemotherapy.

16.
J Control Release ; 321: 159-173, 2020 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-32045622

RESUMO

Compact nanohybrids can potentially unite various therapeutic features and reduce side effects for precise cancer therapy. However, the poor accumulation and limited tumor penetration of drugs at the tumor impede the manifestation of nanomedicine. We developed a rabies virus glycoprotein (RVG)-amplified hierarchical targeted hybrid that acts as a stealthy and magnetolytic carrier that transports dual tumor-penetrating agents incorporating two drugs (boron-doped graphene quantum dots (B-GQDs)/doxorubicin and pH-responsive dendrimers (pH-Den)/palbociclib). The developed RVG-decorated hybrids (RVG-hybrids) enhance the accumulation of drugs at tumor by partially bypassing the BBB via spinal cord transportation and pH-induced aggregation of hierarchical targeting. The penetrated delivery of dual pH-Den and B-GQD drugs to deep tumors is actuated by magnetoelectric effect, which are able to generate electrons to achieve electrostatic repulsion and disassemble the hybrids into components of a few nanometers in size. The synergy of magnetoelectric drug penetration and chemotherapy was achieved by delivery of the B-GQDs and pH-Den to orthotopic tumors, which prolonged the host survival time. This RVG-amplified dual hierarchical delivery integrated with controlled and penetrated release from this hybrid improve the distribution of the therapeutic agents at the brain tumor for synergistic therapy, exhibiting potential for clinic use.


Assuntos
Neoplasias Encefálicas , Grafite , Vírus da Raiva , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina , Sistemas de Liberação de Medicamentos , Glicoproteínas , Humanos
17.
World Neurosurg ; 137: 218-225, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32059963

RESUMO

BACKGROUND: This report presents the third case of trochlear schwannoma arising from the pineal region and the first case to be resected using a paramedian infratentorial supracerebellar approach. Schwannomas of cranial nerves have traditionally been thought to arise from the transitional point where the axonal envelopment switches from glial cells to Schwann cells; however, recent temporal bone histopathologic evidence from vestibular schwannomas challenges this view. Of the 38 cases of pathology-confirmed trochlear schwannoma in the literature, there are only 2 cases arising from the pineal region, where the nerve sheath transition zone is located. Here, we discuss an unusual case of trochlear schwannoma arising from this transition zone. CASE DESCRIPTION: A 65-year-old man was admitted to our institute after a traffic accident. He complained of headache and dizziness, and a computed tomography scan revealed an isodense mass in the pineal region with obstructive hydrocephalus. Magnetic resonance imaging with contrast showed an enhancing mass in the pineal region. The tumor was subtotally resected using a paramedian infratentorial supracerebellar approach, and pathology confirmed the diagnosis of trochlear schwannoma. CONCLUSIONS: Trochlear schwannoma should be considered when a mass is identified in the pineal region. This diagnosis should still be entertained for mass lesions along the free tentorial edge because the tumor may arise distant from the glial-Schwann transition zone located by the dorsal midbrain. We propose a treatment algorithm for this rare tumor that seeks to maximize functional outcome.


Assuntos
Neoplasias dos Nervos Cranianos/cirurgia , Neurilemoma/cirurgia , Procedimentos Neurocirúrgicos , Glândula Pineal , Doenças do Nervo Troclear/cirurgia , Idoso , Angiografia Cerebral , Neoplasias dos Nervos Cranianos/complicações , Neoplasias dos Nervos Cranianos/diagnóstico por imagem , Neoplasias dos Nervos Cranianos/patologia , Tontura/etiologia , Cefaleia/etiologia , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Imageamento por Ressonância Magnética , Masculino , Neurilemoma/complicações , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia , Tomografia Computadorizada por Raios X , Doenças do Nervo Troclear/complicações , Doenças do Nervo Troclear/diagnóstico por imagem , Doenças do Nervo Troclear/patologia
18.
ACS Appl Mater Interfaces ; 11(37): 34305-34315, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31453681

RESUMO

Piezoresistive pressure sensors have garnered significant attention because of their wide applications in automobiles, intelligent buildings, and biomedicine. For in vivo testing, the size of pressure sensors is a vital factor to monitor the pressure of specific portions of a human body. Therefore, the primary focus of this study is to miniaturize piezoresistive pressure sensors with graphene oxide (GO)-incorporated poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) composite films on a flexible substrate for biomedical applications. Prior to the fabrication of pressure sensors, a comprehensive material analysis was applied to identify the horizontal placement of GO flakes within the PEDOT:PSS copolymers, revealing a reduction in variable range hopping distance and an enhancement in carrier mobility. For devices scaled to 0.2 cm, the sensitivity of PEDOT:PSS pressure sensors was conspicuously decreased owing to the late response, which can be effectively solved by GO incorporation. Using technology computer-aided design simulations, the current crowded at the PEDOT:PSS film surface and in the vicinity of an indium-tin-oxide electrode corner was found to be responsible for the changes in piezoresistive behaviors of the scaled devices. The miniaturized flexible piezoresistive pressure sensors with PEDOT:PSS/GO composite films are capable of monitoring the brain pressure of intracranial surgery of a rat and discerning different styles of music for a potential application in hearing aids.

19.
Adv Sci (Weinh) ; 6(16): 1900520, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31453065

RESUMO

Injectable hydrogels in regeneration medicine can potentially mimic hierarchical natural living tissue and fill complexly shaped defects with minimally invasive implantation procedures. To achieve this goal, however, the versatile hydrogels that usually possess the nonporous structure and uncontrollable spatial agent release must overcome the difficulties in low cell-penetrative rates of tissue regeneration. In this study, an adaptable microporous hydrogel (AMH) composed of microsized building blocks with opposite charges serves as an injectable matrix with interconnected pores and propagates gradient growth factor for spontaneous assembly into a complex shape in real time. By embedding gradient concentrations of growth factors into the building blocks, the propagated gradient of the nerve growth factor, integrated to the cell-penetrative connected pores constructed by the building blocks in the nerve conduit, effectively promotes cell migration and induces dramatic bridging effects on peripheral nerve defects, achieving axon outgrowth of up to 4.7 mm and twofold axon fiber intensity in 4 days in vivo. Such AMHs with intrinsic properties of tunable mechanical properties, gradient propagation of biocues and effective induction of cell migration are potentially able to overcome the limitations of hydrogel-mediated tissue regeneration in general and can possibly be used in clinical applications.

20.
Eur J Nucl Med Mol Imaging ; 46(2): 467-477, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30415280

RESUMO

PURPOSE: The role of brain FDG-PET in patients with lung cancer and brain metastases remains unclear. Here, we sought to determine the prognostic significance of whole-body PET/CT plus brain PET/MR in predicting the time to neurological progression (nTTP) and overall survival (OS) in this patient group. METHODS: Of 802 patients with non-small cell lung cancer who underwent primary staging by a single-day protocol of whole-body PET/CT plus brain PET/MR, 72 cases with adenocarcinoma and brain metastases were enrolled for a prognostic analysis of OS. On the basis of the available follow-up brain status, only 52 patients were eligible for prognostic analysis of nTTP. Metastatic brain tumors were identified on post-contrast MR imaging, and the tumor-to-brain ratio (TBR) was measured on PET images. RESULTS: Multivariate analysis revealed that FDG-PET findings and eligibility for initial treatment with targeted therapy were significant independent predictors of nTTP and OS. A new index, termed the molecular imaging prognostic (MIP) score, was proposed to define three disease classes. MIP scores were significant predictors of both nTTP and OS (P < 0.001). Pre-existing prognostic indices such as Lung-molGPA scores were significant predictors of OS but did not predict nTTP. CONCLUSIONS: When staging is performed with whole-body PET/CT plus brain PET/MR, our new prognostic index may be helpful to stratify the outcomes of patients with lung adenocarcinoma and brain metastases. The superior prognostic power of this index for nTTP might be used to select appropriate patients for intracranial control and thereby achieve better quality of life.


Assuntos
Adenocarcinoma de Pulmão/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Encéfalo/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Imagem Corporal Total
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