RESUMO

Glioblastoma (GBM) is the most common primary brain cancer in adults. Despite the remarkable advancements in recent years in the realm of cancer diagnosis and therapy, regrettably, GBM remains the most lethal form of brain cancer. In this view, the fascinating area of nanotechnology has emerged as an innovative strategy for developing novel nanomaterials for cancer nanomedicine, such as artificial enzymes, termed nanozymes, with intrinsic enzyme-like activities. Therefore, this study reports for the first time the design, synthesis, and extensive characterization of innovative colloidal nanostructures made of cobalt-doped iron oxide nanoparticles chemically stabilized by a carboxymethylcellulose capping ligand (i.e., Co-MION), creating a peroxidase-like (POD) nanozyme for biocatalytically killing GBM cancer cells. These nanoconjugates were produced using a strictly green aqueous process under mild conditions to create non-toxic bioengineered nanotherapeutics against GBM cells. The nanozyme (Co-MION) showed a magnetite inorganic crystalline core with a uniform spherical morphology (diameter, 2R = 6-7 nm) stabilized by the CMC biopolymer, producing a hydrodynamic diameter (HD) of 41-52 nm and a negatively charged surface (ZP~-50 mV). Thus, we created supramolecular water-dispersible colloidal nanostructures composed of an inorganic core (Cox-MION) and a surrounding biopolymer shell (CMC). The nanozymes confirmed the cytotoxicity evaluated by an MTT bioassay using a 2D culture in vitro of U87 brain cancer cells, which was concentration-dependent and boosted by increasing the cobalt-doping content in the nanosystems. Additionally, the results confirmed that the lethality of U87 brain cancer cells was predominantly caused by the production of toxic cell-damaging reactive oxygen species (ROS) through the in situ generation of hydroxyl radicals (·OH) by the peroxidase-like activity displayed by nanozymes. Thus, the nanozymes induced apoptosis (i.e., programmed cell death) and ferroptosis (i.e., lipid peroxidation) pathways by intracellular biocatalytic enzyme-like activity. More importantly, based on the 3D spheroids model, these nanozymes inhibited tumor growth and remarkably reduced the malignant tumor volume after the nanotherapeutic treatment (ΔV~40%). The kinetics of the anticancer activity of these novel nanotherapeutic agents decreased with the time of incubation of the GBM 3D models, indicating a similar trend commonly observed in tumor microenvironments (TMEs). Furthermore, the results demonstrated that the 2D in vitro model overestimated the relative efficiency of the anticancer agents (i.e., nanozymes and the DOX drug) compared to the 3D spheroid models. These findings are notable as they evidenced that the 3D spheroid model resembles more precisely the TME of "real" brain cancer tumors in patients than 2D cell cultures. Thus, based on our groundwork, 3D tumor spheroid models might be able to offer transitional systems between conventional 2D cell cultures and complex biological in vivo models for evaluating anticancer agents more precisely. These nanotherapeutics offer a wide avenue of opportunities to develop innovative nanomedicines for fighting against cancerous tumors and reducing the frequency of severe side effects in conventionally applied chemotherapy-based treatments.

RESUMO

The contamination and pollution of wastewater with a wide diversity of chemical, microbiological, and hazardous substances is a field of raising environmental concern. In this study, we developed, for the first time, new hybrid multifunctional nanoplexes composed of ZnS semiconductor quantum dots (ZnS QDs) chemically biofunctionalized with epsilon-poly-l-lysine (ɛPL) and coupled with magnetic iron oxide nanoparticles (MION, Fe3O4) stabilized by carboxymethylcellulose (CMC) for the photodegradation (ZnS) of organic molecules and antibacterial activity (ɛPL) with a potential of recovery by an external magnetic field (Fe3O4). These nanosystems, which were synthesized entirely through a green aqueous process, were comprehensively characterized regarding their physicochemical properties combined with spectroscopic and morphological features. The results demonstrated that supramolecular colloidal nanoplexes were formed owing to the strong cationic/anionic electrostatic interactions between the biomacromolecule capping ligands of the two nanoconjugates (i.e., polypeptide in ZnS@ɛPL and polysaccharide in Fe3O4@CMC). Moreover, these nanosystems showed photocatalytic degradation of methylene blue (MB) used as a model dye pollutant in water. Besides MB, methyl orange, congo red, and rhodamine dyes were also tested for selectivity investigation of the photodegradation by the nanoplexes. The antibacterial activity ascribed to the ɛPL biomolecule was confirmed against Gram-positive and Gram-negative bacteria, including drug-resistance field strains. Hence, it is envisioned that these novel green nanoplexes offer a new avenue of alternatives to be employed for reducing organic pollutants and inactivating pathogenic bacteria in water and wastewater treatment, benefiting from easy magnetic recovery.

Assuntos

Poluentes Ambientais , Pontos Quânticos , Purificação da Água , Pontos Quânticos/química , Corantes/química , Carboximetilcelulose Sódica/química , Polilisina , Antibacterianos , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Nanopartículas Magnéticas de Óxido de Ferro , Água

RESUMO

Diabetic foot ulcers (DFUs) are considered one of the most severe chronic complications of diabetes and can lead to amputation in severe cases. In addition, bacterial infections in diabetic chronic wounds aggravate this scenario by threatening human health. Wound dressings made of polymer matrices with embedded metal nanoparticles can inhibit microorganism growth and promote wound healing, although the current clinical treatments for diabetic chronic wounds remain unsatisfactory. In this view, this research reports the synthesis and characterization of innovative hybrid hydrogels made of carboxymethyl cellulose (CMC) and poly(vinyl alcohol) (PVA) chemically crosslinked by citric acid (CA) functionalized with silver nanoparticles (AgNPs) generated in situ using an eco-friendly aqueous process. The results assessed through comprehensive in vitro and in vivo assays demonstrated that these hybrid polymer hydrogels functionalized with AgNPs possess physicochemical properties, cytocompatibility, hemocompatibility, bioadhesion, antibacterial activity, and biocompatibility suitable for wound dressings to support chronic wound healing process as well as preventing and treating bacterial infections. Hence, it can be envisioned that, with further research and development, these polymer-based hybrid nanoplatforms hold great potential as an important tool for creating a new generation of smart dressings for treating chronic diabetic wounds and opportunistic bacterial infections.

RESUMO

Glioblastoma remains the most lethal form of brain cancer, where hybrid nanomaterials biofunctionalized with polysaccharide peptides offer disruptive strategies relying on passive/active targeting and multimodal therapy for killing cancer cells. Thus, in this research, we report for the first time the rational design and synthesis of novel hybrid colloidal nanostructures composed of gold nanoparticles stabilized by trisodium citrate (AuNP@TSC) as the oxidase-like nanozyme, coupled with cobalt-doped superparamagnetic iron oxide nanoparticles stabilized by carboxymethylcellulose ligands (Co-MION@CMC) as the peroxidase-like nanozyme. They formed inorganic-inorganic dual-nanozyme systems functionalized by a carboxymethylcellulose biopolymer organic shell, which can trigger a biocatalytic cascade reaction in the cancer tumor microenvironment for the combination of magnetothermal-chemodynamic therapy. These nanoassemblies were produced through a green aqueous process under mild conditions and chemically biofunctionalized with integrin-targeting peptide (iRDG), creating bioengineered nanocarriers. The results demonstrated that the oxidase-like nanozyme (AuNP) was produced with a crystalline face-centered cubic nanostructure, spherical morphology (diameter = 16 ± 3 nm), zeta potential (ZP) of -50 ± 5 mV, and hydrodynamic diameter (DH) of 15 ± 1 nm. The peroxide-like nanostructure (POD, Co-MION@CMC) contained an inorganic crystalline core of magnetite and had a uniform spherical shape (2R = 7 ± 1 nm) which, summed to the contribution of the CMC shell, rendered a hydrodynamic diameter of 45 ± 4 nm and a negative surface charge (ZP = -41 ± 5 mV). Upon coupling both nanozymes, water-dispersible colloidal supramolecular vesicle-like organic-inorganic nanostructures were produced (AuNP//Co-MION@CMC, ZP = -45 ± 4 mV and DH = 28 ± 3 nm). They confirmed dual-nanozyme cascade biocatalytic activity targeted by polymer-peptide conjugates (AuNP//Co-MION@CMC_iRGD, ZP = -29 ± 3 mV and DH = 60 ± 4 nm) to kill brain cancer cells (i.e., bioenergy "starvation" by glucose deprivation and oxidative stress through reactive oxygen species generation), which was boosted by the magneto-hyperthermotherapy effect when submitted to the alternating magnetic field (i.e., induced local thermal stress by "nanoheaters"). This groundwork offers a wide avenue of opportunities to develop innovative theranostic nanoplatforms with multiple integrated functionalities for fighting cancer and reducing the harsh side effects of conventional chemotherapy.

RESUMO

Among the most lethal forms of cancer, malignant brain tumors persist as one of the greatest challenges faced by oncologists, where nanotechnology-driven theranostics can play a critical role in developing novel polymer-based supramolecular nanoarchitectures with multifunctional and multi-modal characteristics to fight cancer. However, it is virtually a consensus that, besides the complexity of active delivering anticancer drugs by the nanocarriers to the tumor site, the current evaluation methods primarily relying on in vitro assays and in vivo animal models have been accounted for the low translational effectiveness to clinical applications. In this view, the chick chorioallantoic membrane (CAM) assay has been increasingly recognized as one of the best preclinical models to study the effects of anticancer drugs on the tumor microenvironment (TME). Thus, in this study, we designed, characterized, and developed novel hybrid nanostructures encompassing chemically functionalized carboxymethylcellulose (CMC) with mitochondria-targeting pro-apoptotic peptide (KLA) and cell-penetrating moiety (cysteine, CYS) with fluorescent inorganic semiconductor (Ag-In-S, AIS) for simultaneously bioimaging and inducing glioblastoma cancer cell (U-87 MG, GBM) death. The results demonstrated that the CMC-peptide macromolecules produced supramolecular vesicle-like nanostructures with aqueous colloidal stability suitable as nanocarriers for passive and active targeting of cancer tumors. The optical properties and physicochemical features of the nanoconjugates confirmed their suitability as photoluminescent nanoprobes for cell bioimaging and intracellular tracking. Moreover, the results in vitro demonstrated a notable killing activity towards GBM cells of cysteine-bearing CMC conjugates coupled with pro-apoptotic KLA peptides. More importantly, compared to doxorubicin (DOX), a model anticancer drug in chemotherapy that is highly toxic, these innovative nanohybrids nanoconjugates displayed higher lethality against U-87 MG cancer cells. In vivo CAM assays validated these findings where the nanohybrids demonstrated a significant reduction of GBM tumor progression (41% area) and evidenced an antiangiogenic activity. These results pave the way for developing polymer-based hybrid nanoarchitectonics applied as targeted multifunctional theranostics for simultaneous imaging and therapy against glioblastoma while possibly reducing the systemic toxicity and side-effects of conventional anticancer chemotherapeutic agents.

Assuntos

Antineoplásicos , Neoplasias Encefálicas , Glioblastoma , Pontos Quânticos , Animais , Antineoplásicos/química , Neoplasias Encefálicas/tratamento farmacológico , Carboximetilcelulose Sódica/química , Linhagem Celular Tumoral , Cisteína , Doxorrubicina/química , Glioblastoma/tratamento farmacológico , Nanoconjugados/uso terapêutico , Polímeros/uso terapêutico , Pontos Quânticos/química , Nanomedicina Teranóstica , Microambiente Tumoral

RESUMO

Acute or chronic brain injuries promote deaths and the life-long debilitating neurological status where, despite advances in therapeutic strategies, clinical outcome hardly achieves total patient recovery. In recent decades, brain tissue engineering emerged as an encouraging area of research for helping in damaged central nervous system (CNS) recovery. Polysaccharides are abundant naturally occurring biomacromolecules with a great potential enhancement of advanced technologies in brain tissue repair and regeneration (BTRR). Besides carrying rich biological information, polysaccharides can interact and communicate with biomolecules, including glycosaminoglycans present in cell membranes and many signaling moieties, growth factors, chemokines, and axon guidance molecules. This review includes a comprehensive investigation of the current progress on designing and developing polysaccharide-based soft matter biomaterials for BTRR. Although few interesting reviews concerning BTRR have been reported, this is the first report specifically focusing on covering multiple polysaccharides and polysaccharide-based functionalized biomacromolecules in this emerging and intriguing field of multidisciplinary knowledge. This review aims to cover the state of art challenges and prospects of this fascinating field while presenting the richness of possibilities of using these natural biomacromolecules for advanced biomaterials in prospective neural tissue engineering applications.

Assuntos

Materiais Biocompatíveis/química , Hidrogéis/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Engenharia Biomédica/métodos , Humanos

RESUMO

Overview: Malignant brain tumors remain one of the greatest challenges faced by health professionals and scientists among the utmost lethal forms of cancer. Nanotheranostics can play a pivotal role in developing revolutionary nanoarchitectures with multifunctional and multimodal capabilities to fight cancer. Mitochondria are vital organelles to eukaryotic cells, which have been recognized as a significant target in cancer therapy where, by damaging the mitochondria, it will cause irreparable cell death or apoptosis. Methods: We designed and produced novel hybrid nanostructures comprising a fluorescent semiconductor core (AgInS2, AIS) and cysteine-modified carboxymethylcellulose (termed thiomer, CMC_Cys) conjugated with mitochondria-targeting peptides (KLA) forming a macromolecular shell for combining bioimaging and for inducing brain cancer cell (U-87 MG) death. Results: The optical and physicochemical properties of the nanoconjugates demonstrated suitability as photoluminescent nanostructures for cell bioimaging and intracellular tracking. Additionally, the results proved a remarkable killing activity towards glioblastoma cells of cysteine-bearing CMC conjugates coupled with KLA peptides through the half-maximal effective concentration values, approximately 70-fold higher compared to the conjugate analogs without Cys residues. Moreover, these thiomer-based pro-apoptotic drug nanoconjugates displayed higher lethality against U-87 MG cancer cells than doxorubicin, a model drug in chemotherapy, although extremely toxic. Remarkably, these peptidomimetic nanohybrids demonstrated a relative "protective effect" regarding healthy cells while maintaining high killing activity towards malignant brain cells. Conclusion: These findings pave the way for developing hybrid nanoarchitectures applied as targeted multifunctional platforms for simultaneous imaging and therapy against cancer while minimizing the high systemic toxicity and side-effects of conventional drugs in anticancer chemotherapy.

Assuntos

Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/patologia , Corantes Fluorescentes/química , Mitocôndrias/efeitos dos fármacos , Nanotecnologia , Peptidomiméticos , Medicina de Precisão/métodos , Linhagem Celular Tumoral , Humanos

RESUMO

In this work, it was developed three-dimensional (3D) porous hydrogel sponges produced by the freeze-dried process using chitosan polymer functionalized by 11-mercaptoundecanoic acid (MUA). These chitosan-based sponges were used as cationic adsorbents for the removal of anionic methyl orange (MO) dye, simulating a model organic pollutant in aqueous medium. Moreover, these porous 3D constructs were also evaluated as 'antibiotic-free' antibacterial materials against gram-negative and gram-positive bacteria, Pseudomonas aeruginosa and Staphylococcus aureus, respectively, which were used as model pathogens possibly found in contaminated hospital discharges. These 3D hydrogels were comprehensively characterized through morphological methods such as scanning electron microscopy and X-ray micro-computed tomography techniques, combined with FTIR, Raman, and UV-visible spectroscopy analyses. Additionally, the surface area, the degree of swelling, and the adsorption profiles and kinetics of these scaffolds were systematically investigated. The chemically thiolated chitosan (CHI-MUA) hydrogels were successfully produced with a supramolecular polymeric network based on hydrogen bonds, disulfide bonds, and hydrophobic interactions that resulted in higher stability in aqueous medium than hydrogels of pristine chitosan. CHI-MUA exhibited sponge-like three-dimensional structures, with highly interconnected and hierarchical pore size distribution with high porosity and surface area. These architectural aspects of the 3D sponges favoured the high adsorption capacity for MO dye (∼388 mg.g-1) in water with removal efficiency greater than 90% for MO solutions (from 20 mg.L-1-1200 mg.L-1). The adsorption data followed a pseudo-second-order kinetic model and adsorption isotherm analysis and spectroscopy studies suggested a multilayer behaviour with coexistence of adsorbent-adsorbate and adsorbate-adsorbate interactions. Additionally, the in vitro evaluation of toxicity (MTT and LIVE-DEAD® assays) of 3D-sponges revealed a non-toxic response and preliminary suitability for bio-related applications. Importantly, the 3D-sponges composed of chitosan-thiolated derivative proved high antibacterial activity, specificity against P. aeruginosa (model hazardous pathogen), equivalent to conventional antibiotic drugs, while no lethality against S. aureus (reference commensal bacteria) was observed.

Assuntos

Quitosana , Poluentes Químicos da Água , Adsorção , Antibacterianos/farmacologia , Concentração de Íons de Hidrogênio , Cinética , Staphylococcus aureus , Microtomografia por Raio-X

RESUMO

The earliest possible diagnosis and understanding of the infection mechanisms play a crucial role in the outcome of fighting viral diseases. Thus, we designed and developed for the first time, novel bioconjugates made of Ag-In-S@ZnS (ZAIS) fluorescent quantum dots coupled with ZIKA virus via covalent amide bond with carboxymethylcellulose (CMC) biopolymer for labeling and bioimaging the virus-host cell interactions mechanisms through confocal laser scanning microscopy. This work offers relevant insights regarding the profile of the ZIKA virus-nanoparticle conjugates interactions with VERO cells, which can be applied as a nanoplatform to elucidate the infection mechanisms caused by this viral disease.

RESUMO

Despite the undeniable advances in recent decades, cancer remains one of the deadliest diseases of the current millennium, where the triple-negative breast cancer (TNBC) is very aggressive, extremely metastatic, and resistant to conventional chemotherapy. The nanotheranostic approach focusing on targeting membrane receptors often expressed at abnormal levels by cancer cells can be a strategic weapon for fighting malignant tumors. Herein, we introduced a novel "all-in-one nanosoldier" made of colloidal hybrid nanostructures, which were designed for simultaneously targeting, imaging, and killing TNBC cells. These nanohybrids comprised four distinct components: (a) superparamagnetic iron oxide nanoparticles, as bi-functional nanomaterials for inducing ferroptosis via inorganic nanozyme-mediated catalysis and magnetotherapy by hyperthermia treatment; (b) carboxymethyl cellulose biopolymer, as a water-soluble capping macromolecule; (c) folic acid, as the membranotopic vector for targeting folate receptors; (d) and doxorubicin (DOX) drug for chemotherapy. The results demonstrated that this novel strategy was highly effective for targeting and killing TNBC cells in vitro, expressing high levels of folate membrane-receptors. The results evidenced that three integrated mechanisms triggered the deaths of the cancer cells in vitro: (a) ferroptosis, by magnetite nanoparticles inducing a Fenton-like reaction; (b) magneto-hyperthermia effect by generating heat under an alternate magnetic field; and (c) chemotherapy, through the DOX intracellular release causing DNA dysfunction. This "all-in-one nanosoldier" strategy offers a vast realm of prospective alternatives for attacking cancer cells, combining multimodal therapy and the delivery of therapeutic agents to diseased sites and preserving healthy cells, which is one of the most critical clinical challenges faced in fighting drug-resistant breast cancers.

Assuntos

Antineoplásicos/química , Doxorrubicina/química , Corantes Fluorescentes/química , Nanopartículas de Magnetita/química , Nanocápsulas/química , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/terapia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Terapia Combinada , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Liberação Controlada de Fármacos , Receptores de Folato com Âncoras de GPI/metabolismo , Ácido Fólico/química , Ácido Fólico/metabolismo , Humanos , Hipertermia Induzida/efeitos adversos , Campos Magnéticos , Nanopartículas de Magnetita/uso terapêutico , Terapia de Alvo Molecular , Imagem Óptica , Estudos Prospectivos , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica

RESUMO

Purpose: Disturbances that affect the inside of the eyeball tend to be highly harmful since they compromise the homeostasis of this organ. Alongside this, the eyeball has several anatomical barriers that prevent the entry of substances. This way, diseases that affect the retina are among those that present greater difficulty in the treatment. In many cases, abnormal proliferation of blood vessels (neovascularization) occurs from the lower layers of the retina. This process damages its structure physiologically and anatomically, causing the rapid and irreversible loss of visual capacity. This work aims to develop nanosuspensions of quantum dots (QDs) conjugated to bevacizumab. Methods: Two types of QDs were produced by aqueous route, stabilized with chitosan conjugated to bevacizumab. The antiangiogenic activity was evaluated in the chorioallantoic membrane model, in which results indicated discrete activity at the doses tested. Samples were assessed for their biosafety in animals, after intravitreal administration, by means of electroretinography (ERG), intraocular pressure (IOP) measurement, histological, morphometric, and immunohistochemical evaluation. Results: No significant alterations were detected in ERG that suggests damage to retinal function by the samples. No significant changes in IOP were also detected. The histological sections did not show signs of acute inflammation, although there was evidence of late retinal damage. The immunohistochemical analysis did not detect any apoptotic bodies. Conclusion: Preliminary results suggest that QDs present potential applicability in ocular therapy, and it is necessary to better characterize their in vivo behavior and to optimize their dosage.

Assuntos

Inibidores da Angiogênese/farmacologia , Bevacizumab/farmacologia , Pontos Quânticos/uso terapêutico , Retina/patologia , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Animais , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêutico , Membrana Corioalantoide/efeitos dos fármacos , Contenção de Riscos Biológicos/normas , Eletrorretinografia/métodos , Imuno-Histoquímica/métodos , Pressão Intraocular/efeitos dos fármacos , Injeções Intravítreas , Masculino , Modelos Animais , Nanopartículas/química , Nanopartículas/uso terapêutico , Neovascularização Patológica/diagnóstico , Neovascularização Patológica/tratamento farmacológico , Pontos Quânticos/administração & dosagem , Pontos Quânticos/química , Ratos , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/metabolismo , Suspensões/administração & dosagem , Suspensões/química , Suspensões/farmacocinética , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/farmacologia , Fator A de Crescimento do Endotélio Vascular/imunologia

RESUMO

Glioblastoma (GBM) is the utmost aggressive and lethal primary brain cancer, which has a poor prognosis and remains virtually incurable. Nanomedicine with emerging disruptive nanotechnology alternatives, including designed supramolecular nanohybrids has excellent potential as multimodal tools against cancer by combining nanomaterials, biomacromolecules, and drugs. Thus, we developed and constructed for the first time quantum dot-biopolymer-drug nanohybrids based on host-guest chemistry for simultaneous bioimaging, targeting, and anti-cancer drug delivery against GBM cells in vitro. ZnS fluorescent quantum dots (ZnS-QDs) were produced using chemically modified polysaccharide, carboxymethylcellulose (CMC), as water-soluble capping ligand and biofunctional layer via a facile one-step eco-friendly aqueous colloidal process at room temperature and physiological pH. These hybrid inorganic-organic nanocolloids (ZnS@CMC) were electrostatically conjugated with doxorubicin (DOX) anti-cancer drug forming innovative supramolecular complexes (ZnS@CMC-DOX) for amalgamating bioimaging and killing cancer cells. These nanoconjugates were characterized regarding their optical and physicochemical properties combined with morphological and structural features. The cytocompatibility was evaluated by MTT assay using healthy and GBM cells. The results showed that ultra-small ZnS-QDs were expertly produced uniform nanocolloids (average size = 3.6 nm). They demonstrated photoluminescence emission within the visible range of spectra. The cell viability results in vitro showed no cytotoxicity of ZnS@CMC nanohybrids towards both cell types. In summary, the novelty of this research relies on using a nanotheranostic strategy for developing ZnS@CMC-DOX nanohybrids with supramolecular vesicle-like structures. They behaved simultaneously as active fluorescent nanoprobes and nanocarriers with modulated drug release for bioimaging and killing malignant glioma cells proving the high potential for applications in cancer nanomedicine.

Assuntos

Antibióticos Antineoplásicos/farmacologia , Biopolímeros/química , Neoplasias Encefálicas/tratamento farmacológico , Doxorrubicina/farmacologia , Glioblastoma/tratamento farmacológico , Imagem Óptica , Pontos Quânticos/química , Antibióticos Antineoplásicos/química , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Ensaios de Seleção de Medicamentos Antitumorais , Glioblastoma/metabolismo , Glioblastoma/patologia , Células HEK293 , Humanos , Substâncias Macromoleculares/química , Nanopartículas/química , Tamanho da Partícula , Propriedades de Superfície

RESUMO

Novel core-shell superparamagnetic nanofluids composed of magnetic iron oxide (Fe3O4, MION) and cobalt-doped (CoxFe3-xO4, Co-MION) nanoparticles functionalized with carboxymethyl cellulose (CMC) ligands were designed and produced via green colloidal aqueous process. The effect of the degree of substitution (DS = 0.7 and 1.2) and molecular mass (Mw) of CMC and cobalt doping concentration on the physicochemical and magnetic properties of these nanoconjugates were comprehensively investigated using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction, transmission electron microscopy (TEM) with selected area electron diffraction, X-ray fluorescence, dynamic light scattering (DLS), zeta potential (ZP) analysis, vibrating sample magnetometry (VSM) and electron paramagnetic resonance spectroscopy (EPR). The results demonstrated the effect of concentration of carboxylate groups and Mw of CMC on the hydrodynamic dimension, zeta potential, and generated heat by magnetic hyperthermia of MION nanoconjugates. Co-doping of MION showed significant alteration of the electrostatic balance of charges of the nanoconjugates interpreted as effect of surface interactions. Moreover, the VSM and EPR results proved the superparamagnetic properties of these nanocolloids, which were affected by the presence of CMC and Co-doping of iron oxide nanoparticles. These magnetic nanohybrids behaved as nanoheaters for killing brain cancer cells in vitro with prospective future applications in oncology and nanomedicine.

Assuntos

Carboximetilcelulose Sódica/química , Carboximetilcelulose Sódica/farmacologia , Nanopartículas de Magnetita/química , Nanocompostos/química , Carboximetilcelulose Sódica/síntese química , Linhagem Celular Tumoral , Técnicas de Química Sintética , Humanos , Fenômenos Magnéticos , Nanotecnologia

RESUMO

Glioblastoma is the most aggressive primary brain cancer, which has no cure yet. Emerging nanotheranostic alternatives such as magnetic iron oxide nanoparticles (MIONs) have great potential as multimodal cancer therapy mediators. They can act as nanocarriers of anticancer drugs and generate localized heat when exposed to an alternating magnetic field (AMF), resulting in combined effects of chemotherapy and magnetic hyperthermia therapy. Thus, we designed and synthesized novel MIONs directly through a co-precipitation method by a single step one-pot aqueous green process using carboxymethylcellulose (CMC) as a multifunctional, biocompatible and water-soluble biopolymer ligand (iron oxide nanoparticle-CMC, MION@CMC). They were bioconjugated via amide bonds with doxorubicin (DOX, an anticancer drug) forming nanohybrids (MION@CMC-DOX). The CMC, MION@CMC and MION@CMC-DOX nanoconjugates were comprehensively characterized by 1HNMR, FTIR, TEM/SAED/EDX, UV-visible, XRD, zeta potential (ZP) and DLS analyses. Moreover, cytotoxicity and cell killing activities of these nanoconjugates were assessed by in vitro biological assays. The nanoconjugates were incubated with glioma cells (U87), a magnetic hyperthermia (MHT) assay was performed for evaluating the activity against brain cancer cells and confocal laser scanning laser microscopy was used for bioimaging their cellular uptake pathways. The results showed that fairly monodisperse and water-soluble ultra-small iron oxide nanoparticles (Fe3O4) were synthesized (core size = 7 ± 2 nm) and stabilized by CMC producing negatively charged nanocolloids (-38 ± 3 mV, MION@CMC; hydrodynamic radius, HD = 38 ± 2 nm). The results confirmed the conjugation of MION@CMC with DOX by amide bonds, leading to the development of magnetopolymersome nanostructures (MION@CMC-DOX). The cell viability bioassays evidenced low toxicity of MION@CMC compared to the severe cytotoxicity of MION@CMC-DOX nanosystems mainly caused by the release of DOX. Under an alternating magnetic field, MION@CMC and MION@CMC-DOX systems demonstrated activity for killing U87 cancer cells due to the heat generated by hyperthermia. In addition, the MION@CMC-DOX bioconjugates showed significantly higher cell killing response when exposed to an AMF due to the combined chemotherapy effect of DOX release inside the cancer cells triggering apoptotic pathways.

Assuntos

Antineoplásicos/química , Neoplasias Encefálicas/patologia , Carboximetilcelulose Sódica/química , Doxorrubicina/química , Hipertermia Induzida , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transporte Biológico , Neoplasias Encefálicas/tratamento farmacológico , Fenômenos Químicos , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Óxido Ferroso-Férrico/química , Células HEK293 , Humanos , Modelos Moleculares , Conformação Molecular , Nanopartículas/química

RESUMO

Many human diseases, including metabolic, immune, and central nervous system disorders, as well as several types of cancers, are the consequence of an important alteration in lipid-related metabolic biomolecules. Although recognized that one of the most important metabolic hallmarks of cancer cells is deregulation of lipid metabolism, the multiple complex signaling pathways are poorly understood yet. Thus, in this research, novel nanoconjugates made of ZnS quantum dots (QDs) were directly synthesized in aqueous media using phosphoethanolamine (PEA) as the capping ligand, which is an important biomolecule naturally present in cells for de novo biosynthesis of fatty acids and phospholipids involved in the cell structure (e.g., membrane), differentiation, and cancer growth. These QD-PEA bio-nanoconjugates were characterized by spectroscopical and morphological techniques. The results demonstrated that fluorescent ZnS nanocrystalline QDs were produced with uniform spherical morphology and estimated sizes of 3.3 ± 0.6 nm. These nanoconjugates indicated core-shell colloidal nanostructures (ZnS QD-PEA) with the hydrodynamic diameter (H D) of 26.0 ± 3.5 nm and ζ-potential centered at -30.0 ± 4.5 mV. The cell viability response using mitochondrial activity assay in vitroconfirmed no cytotoxicity at several concentrations of PEA (biomolecule) and the ZnS-PEA nanoconjugates. Moreover, these nanoconjugates effectively behaved as fluorescent nanomarkers for tracking the endocytic pathways of cancer cells using confocal laser scanning microscopy bioimaging. Hence, these results proved that biofunctionalized ZnS-PEA nanoprobes offer prospective tools for cellular bioimaging with encouraging forecast for future applications as active fluorescent biomarker conjugates in metabolic-related cancer research.

RESUMO

In this study, new eco-friendly hydrogel adsorbents were synthesized based on carboxymethylcellulose (CMC, degree of substitution [DS] = 0.7) chemically cross-linked with citric acid (CA) using a green process in aqueous solution and applied for the adsorption of methylene blue (MB). Spectroscopic analyses demonstrated the mechanism of cross-linking through the reaction of hydroxyl functional groups from CMC with CA. These CMC hydrogels showed very distinct morphological features dependent on the extension of cross-linking and their nanomechanical properties were drastically increased by approximately 300% after cross-linking with 20% CA (e.g. elastic moduli from 80 ± 15 to 270 ± 50 MPa). Moreover, they were biocompatible using an in vitro cell viability assay in contact with human osteosarcoma-derived cells (SAOS) for 24 h. These CMC-based hydrogels exhibited adsorption efficiency above 90% (24 h) and maximum removal capacity of MB from 5 to 25 mg g-1 depending on the dye concentration (from 100 to 500 mg L-1), which was used as the model cationic organic pollutant. The adsorption of process of MB was well-fit to the pseudo-second-order kinetics model. The desorption of MB by immersion in KCl solution (3 mol L-1, 24 h) showed a typical recovery efficiency of over 60% with conceivable reuse of these CMC-based hydrogels. Conversely, CMC hydrogels repelled methyl orange dye used as model anionic pollutant, proving the mechanism of adsorption by the formation of charged polyelectrolyte/dye complexes.

Assuntos

Poluentes Ambientais , Poluentes Químicos da Água , Adsorção , Carboximetilcelulose Sódica , Corantes , Humanos , Hidrogéis

RESUMO

This study focused on the synthesis and comprehensive characterization of environmentally friendly hydrogel membranes based on carboxymethyl cellulose (CMC) for wound dressing and skin repair substitutes. These new CMC hydrogels were prepared with two degrees of functionalization (DS=0.77 and 1.22) and chemically crosslinked with citric acid (CA) for tuning their properties. Additionally, CMC-based hybrids were prepared by blending with polyethylene glycol (PEG, 10wt.%). The results demonstrated that superabsorbent hydrogels (SAP) were produced with swelling degree typically ranging from 100% to 5000%, which was significantly dependent on the concentration of CA crosslinker and the addition of PEG as network modifier. The spectroscopical characterizations indicated that the mechanism of CA crosslinking was mostly associated with the chemical reaction with CMC hydroxyl groups and that PEG played an important role on the formation of a hybrid polymeric network. These hydrogels presented very distinct morphological features depended on the degree of crosslinking and the surface nanomechanical properties (e.g., elastic moduli) were drastically affected (from approximately 0.08GPa to 2.0GPa) due to the formation of CMC-PEG hybrid nanostructures. These CMC-based hydrogels were cytocompatible considering the in vitro cell viability responses of over 95% towards human embryonic kidney cells (HEK293T) used as model cell line.

Assuntos

Bandagens/microbiologia , Materiais Biocompatíveis/química , Carboximetilcelulose Sódica/química , Polietilenoglicóis/química , Materiais Biocompatíveis/uso terapêutico , Carboximetilcelulose Sódica/uso terapêutico , Reagentes de Ligações Cruzadas/química , Reagentes de Ligações Cruzadas/uso terapêutico , Células HEK293 , Humanos , Hidrogéis/química , Hidrogéis/uso terapêutico , Polietilenoglicóis/uso terapêutico , Cicatrização/efeitos dos fármacos

RESUMO

Colloidal semiconductor quantum dots (QDs) are light-emitting ultra-small nanoparticles, which have emerged as a new class of nanoprobes with unique optical properties for bioimaging and biomedical diagnostic. However, to be used for most biomedical applications the biocompatibility and water-solubility are mandatory that can achieved through surface modification forming QD-nanoconjugates. In this study, semiconductor II-VI quantum dots of type MX (M=Cd, Pb, Zn, X=S) were directly synthesized in aqueous media and at room temperature using carboxymethylcellulose sodium salt (CMC) behaving simultaneously as stabilizing and surface biofunctional ligand. These nanoconjugates were extensively characterized using UV-visible spectroscopy, photoluminescence spectroscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, dynamic light scattering and zeta potential. The results demonstrated that the biopolymer was effective on nucleating and stabilizing the colloidal nanocrystals of CdS, ZnS, and PbS with the average diameter ranging from 2.0 to 5.0nm depending on the composition of the semiconductor core, which showed quantum-size confinement effect. These QD/polysaccharide conjugates showed luminescent activity from UV-visible to near-infrared range of the spectra under violet laser excitation. Moreover, the bioassays performed proved that these novel nanoconjugates were biocompatible and behaved as composition-dependent fluorescent nanoprobes for in vitro live cell bioimaging with very promising perspectives to be used in numerous biomedical applications and nanomedicine.

Assuntos

Bioengenharia/métodos , Carboximetilcelulose Sódica/química , Corantes Fluorescentes/química , Imageamento Tridimensional , Sondas Moleculares/química , Nanoconjugados/química , Pontos Quânticos/química , Semicondutores , Sobrevivência Celular , Células HEK293 , Humanos , Nanoconjugados/ultraestrutura , Espectroscopia Fotoeletrônica , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X

RESUMO

Cancer research has experienced astonishing advances recently, but cancer remains a major threat because it is one of the leading causes of death worldwide. Glioblastoma (GBM) is the most malignant brain tumor, where the early diagnosis is vital for longer survival. Thus, this study reports the synthesis of novel water-dispersible ternary AgInS2 (AIS) and quaternary AgInS2-ZnS (ZAIS) fluorescent quantum dots using carboxymethylcellulose (CMC) as ligand for multiplexed bioimaging of malignant glioma cells (U-87 MG). Firstly, AgInS2 core was prepared using a one-pot aqueous synthesis stabilized by CMC at room temperature and physiological pH. Then, an outer layer of ZnS was grown and thermally annealed to improve their optical properties and split the emission range, leading to core-shell alloyed nanostructures. Their physicochemical and optical properties were characterized, demonstrating that luminescent monodispersed AIS and ZAIS QDs were produced with average sizes of 2.2 nm and 4.3 nm, respectively. Moreover, the results evidenced that they were cytocompatible using in vitro cell viability assays towards human embryonic kidney cell line (HEK 293T) and U-87 MG cells. These AIS and ZAIS successfully behaved as fluorescent nanoprobes (red and green, resp.) allowing multiplexed bioimaging and biolabeling of costained glioma cells using confocal microscopy.

Assuntos

Polímeros/química , Pontos Quânticos/química , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Glioblastoma , Células HEK293 , Humanos , Microscopia Confocal

RESUMO

Quantum dots (QDs) are colloidal semiconductor nanocrystals with unique properties that can be engineered by controlling the nanoparticle size and chemical composition by doping and alloying strategies. However, due to their potential toxicity, augmenting their biocompatibility is yet a challenge for expanding to several biomedical and environmentally friendly applications. Thus, the main goal of this study was to develop composition-tunable and biocompatible Zn x Cd1 - x S QDs using carboxymethylcellulose polysaccharide as direct capping ligand via green colloidal aqueous route at neutral pH and at room temperature for potential biomedical and environmental applications. The ternary alloyed QDs were extensively characterized using UV-vis spectroscopy, photoluminescence spectroscopy (PL), transmission electron microscopy (TEM), X-ray diffraction (XRD), electron energy loss spectroscopy (EELS), and X-ray photoelectrons spectroscopy (XPS). The results indicated that Zn x Cd(1 - x)S QDs were surface stabilized by carboxymethylcellulose biopolymer with spherical morphology for all composition of alloys and narrow sizes distributions ranging from 4 to 5 nm. The XRD results indicated that monophasic ternary alloyed Zn x Cd1 - x S nanocrystals were produced with homogenous composition of the core as evidenced by EELS and XPS analyses. In addition, the absorption and emission optical properties of Zn x Cd1 - x S QDs were red shifted with increasing the amount of Cd2+ in the alloyed nanocrystals, which have also increased the quantum yield compared to pure CdS and ZnS nanoparticles. These properties of alloyed nanomaterials were interpreted based on empirical model of Vegard's law and chemical bond model (CBM). As a proof of concept, these alloyed-QD conjugates were tested for biomedical and environmental applications. The results demonstrated that they were non-toxic and effective fluorophores for bioimaging live HEK293T cells (human embryonic kidney cells) using confocal laser scanning fluorescence microscopy. Moreover, these conjugates presented photocatalytic activity for photodegradation of methylene blue used as model organic industrial pollutant in water. Hence, composition-tunable optical properties of ternary Zn x Cd1 - x S (x = 0-1) fluorescent alloyed QDs was achieved using a facile eco-friendly aqueous processing route, which can offer promising alternatives for developing innovative nanomaterials for applications in nanomedicine and environmental science and technology.