RESUMO
Hair dyeing has become a prevalent lifestyle trend, especially within the fashion industry. However, it possesses disadvantages, such as containing carcinogenic and toxic materials. In this study, we developed a biocompatible hair-dyeing technology using a shampoo with a dark polyphenol complex (DPC), referred to as S-DPC. The DPC was formed from a mixture of gallic acid and [1,1'-biphenyl]-2,2',4,4',5,5'-hexol and used to enhance both the stability of the hair coating and its ability to scavenge reactive oxygen species (ROS). Colloidal DPC particles play a pivotal role in the coating process of various hair dyes, ensuring the uniform coloring of human hair through intermolecular interactions such as hydrogen bonding. Owing to the effect of a polyphenol complex on hair coating, we observed improved antistatic performance and enhanced mechanical strength, resulting in a substantial increase in elongation at the breaking point from 33.74% to 48.85%. The multicolor S-DPC exhibited antioxidant properties, as indicated by its ROS-scavenging ability, including 2,2-diphenyl-1-picrylhydrazyl inhibition (87-89%), superoxide radical scavenging (84-87%), and hydroxyl radical scavenging (95-98%). Moreover, the in vitro analysis of the DPC revealed nearly 100% cell viability in live and dead assays, highlighting the remarkable biocompatibility of the DPC. Therefore, considering its effectiveness and safety, this biomaterial has considerable potential for applications in hair dyeing.
RESUMO
Herein, a cancer-specific dopamine-conjugated sp2-rich carbonized polymer dot (PD)-encapsulated mesoporous MnO2 (MnO2@PD)-mineralized hydrogel biosensor was developed that offers cancer-induced observable in situ alterations in fluorescence (FL), electrochemical, and mechanophysical properties. Cancer-triggered MnO2 degradation in the hydrogel, prompted by increased levels of glutathione (GSH) and reactive oxygen species (ROS) such as H2O2, leads to PD release and FL restoration, thereby controlling changes in the pore structure and increasing hydrogen bonding, resulting in physiologically visible alterations in mechanical stretchability, viscosity, swelling behavior, and adhesiveness. The pore size of the matrix increased from 21.83 to 36.81 m2/g upon GSH treatment, affecting the viscosity and swellability of the system. The resistance increased from 21.96 ± 1.16 to 30.69 ± 2.01 and 32.21 ± 2.54 kΩ, respectively, confirming the dependence of conductivity changes on H2O2 and GSH treatments. The in vitro treatment with cancer cells (HeLa, PC-3, and B16F10) facilitated a tunable electrochemical sensing performance via redox-mediated MnO2 breakdown by intracellular ROS and GSH, whereas hydrogels treated with normal cells (CHO-K1) showed minimal changes. Cancer-microenvironment-derived water-drop sensing showed three times higher response as compared to the normal cell-treated hydrogel. The sensing capability of the fabricated sensor was validated based on bending-induced relative resistance changes under dry and wet conditions. Moreover, the integration of the developed sensor with a wireless sensor enabled real-time monitoring with a smartphone.
Assuntos
Hidrogéis , Neoplasias , Humanos , Polímeros , Compostos de Manganês/química , Adesividade , Peróxido de Hidrogênio , Espécies Reativas de Oxigênio , Óxidos/química , Glutationa , Neoplasias/tratamento farmacológicoRESUMO
In this study, we developed a hair-coating polyphenol complex (PPC) that showed ultraviolet (UV) protection properties, antistatic features, and the capability to enhance the mechanical strength of damaged hair. PPCs prepared with different ratios of tannic acid (TA), gallic acid (GA), and caffeic acid (CA) simultaneously increased the self-recovery of damaged hair by protecting the cuticle. PPC prevented light from passing through the damaged hair during exposure to UV radiation. Moreover, surfaces coated with PPC1 (TA:GA:CA, 100:20:0.5) exhibited a higher conductivity than surfaces coated with PPCs with other ratios of TA, GA, and CA, with a resistance of 0.72 MΩ. This influenced the antistatic performance of the surface, which exhibited no electrical attraction after being subjected to an electrostatic force. Additionally, damaged hair exhibited a significant increase in durability and elasticity after coating with a PPC1-containing shampoo, with a tensile strain of up to 2.06× post-treatment, indicating the recovery of the damaged cuticle by the PPC complex. Furthermore, PPC1-containing shampoo prevented damage by scavenging excess reactive oxygen species in the hair. The combination effect promoted by the natural PPC offers new insights into hair treatment and paves the way for further exploration of hair restoration technology.
RESUMO
Light-based therapy such as photobiomodulation (PBM) reportedly produces beneficial physiological effects in cells and tissues. However, most reports have focused on the immediate and instant effects of light. Considering the physiological effects of natural light exposure in living organisms, the latent reaction period after irradiation should be deliberated. In contrast to previous reports, we examined the latent reaction period after light exposure with optimized irradiating parameters and validated novel therapeutic molecular mechanisms for the first time. we demonstrated an organic light-emitting diode (OLED)-based PBM (OPBM) strategy that enhances the angiogenic efficacy of human adipose-derived stem cells (hADSCs) via direct irradiation with red OLEDs of optimized wavelength, voltage, current, luminance, and duration, and investigated the underlying molecular mechanisms. Our results revealed that the angiogenic paracrine effect, viability, and adhesion of hADSCs were significantly intensified by our OPBM strategy. Following OPBM treatment, significant changes were observed in HIF-1α expression, intracellular reactive oxygen species levels, activation of the receptor tyrosine kinase, and glycolytic pathways in hADSCs. In addition, transplantation of OLED-irradiated hADSCs resulted in significantly enhanced limb salvage ratio in a mouse model of hindlimb ischemia. Our OPBM might serve as a new paradigm for stem cell culture systems to develop cell-based therapies in the future.
RESUMO
This study investigated a selective and sensitive theragnosis system for the specific targeting of the membrane and nuclei based on visible-light and pH-responsive TiO2-integrated cross-linked carbon dot (C-CD/TiO2) for tumor detection and controllable photothermal therapy. The cross-linking system was formed by boronate ester linkages between the TiO2-immobilized Dopa-decyl (D-CD) and zwitterionic-formed CD (Z-CD) for nuclear targeting, which showed fluorescence "off" at physiological pH. The fluorescence recovered to the "on" state in acidic cancer cells owing to cleavages of the boronate ester bonds, resulting in the disruption of the Förster resonance energy transfer that generated different CDs useful for tumor-selective biosensors and therapy. D-CD, which is hydrophobic, can penetrate the hydrophobic sites of the cell membrane; it caused a loss in the hydrophobicity of these sites after visible-light irradiation. This was achieved by the photocatalytic activity of the TiO2 modulating energy bandgap, whereas the Z-CD targeted the nucleus, as confirmed by merged confocal microscopy images. D-CD augmented by photothermal heat also exhibited selective anticancer activity in the acidic tumor condition but showed only minimal effects at a normal site at pH 7.4. After C-CD/TiO2 injection to an in vivo tumor model, C-CD/TiO2 efficiently ablated tumors under NIR light irradiation. The C-CD/TiO2 group showed up-regulation of the pro-apoptotic markers such as P53 and BAX in tumor. This material exhibited its potential as a theragnostic sensor with excellent biocompatibility, high sensitivity, selective imaging, and direct anticancer activity via photothermal therapy.
Assuntos
Raios Infravermelhos , Luz , Pontos Quânticos/química , Titânio/química , Animais , Carbono/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Transferência Ressonante de Energia de Fluorescência , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Nus , Microscopia Confocal , Neoplasias/patologia , Neoplasias/terapia , Terapia Fototérmica , Pontos Quânticos/uso terapêutico , Pontos Quânticos/toxicidade , Transplante HeterólogoRESUMO
Recently, a great deal of research has focused on the study of self-healing hydrogels possessing electronic conductivity due to their wide applicability for use in biosensors, bioelectronics, and energy storage. The low solubility, poor biocompatibility, and lack of effective stimuli-responsive properties of their sp2 carbon-rich hybrid organic polymers, however, have proven challenging for their use in electroconductive self-healing hydrogel fabrication. In this study, we developed stimuli-responsive electrochemical wireless hydrogel biosensors using ureidopyriminone-conjugated gelatin (Gel-UPy) hydrogels that incorporate diselenide-containing carbon dots (dsCD) for cancer detection. The cleavage of diselenide groups of the dsCD within the hydrogels by glutathione (GSH) or reactive oxygen species (ROS) initiates the formation of hydrogen bonds that affect the self-healing ability, conductivity, and adhesiveness of the Gel-UPy/dsCD hydrogels. The Gel-UPy/dsCD hydrogels demonstrate more rapid healing under tumor conditions (MDA-MB-231) compared to that observed under physiological conditions (MDCK). Additionally, the cleavage of diselenide bonds affects the electrochemical signals due to the degradation of dsCD. The hydrogels also exhibit excellent adhesiveness and in vivo cancer detection ability after exposure to a high concentration of GSH or ROS, and this is comparable to results observed in a low concentration environment. Based on the combined self-healing, conductivity, and adhesiveness properties of the Gel-UPy/dsCD, this hydrogel exhibits promise for use in biomedical applications, particularly those that involve cancer detection, due to its selectivity and sensitivity under tumor conditions.
Assuntos
Hidrogéis , Neoplasias , Adesivos , Carbono , Condutividade Elétrica , GelatinaRESUMO
Previous work has demonstrated that fusion of a luciferase to an opsin, to create a luminescent opsin or luminopsin, provides a genetically encoded means of manipulating neuronal activity via both chemogenetic and optogenetic approaches. Here we have expanded and refined the versatility of luminopsin tools by fusing an alternative luciferase variant with high light emission, Gaussia luciferase mutant GLucM23, to depolarizing and hyperpolarizing channelrhodopsins with increased light sensitivity. The combination of GLucM23 with Volvox channelrhodopsin-1 produced LMO4, while combining GLucM23 with the anion channelrhodopsin iChloC yielded iLMO4. We found efficient activation of these channelrhodopsins in the presence of the luciferase substrate, as indicated by responses measured in both single neurons and in neuronal populations of mice and rats, as well as by changes in male rat behavior during amphetamine-induced rotations. We conclude that these new luminopsins will be useful for bimodal opto- and chemogenetic analyses of brain function.
Assuntos
Channelrhodopsins , Luciferases , Neurônios/fisiologia , Optogenética/métodos , Potenciais de Ação , Adenoviridae/fisiologia , Animais , Channelrhodopsins/genética , Channelrhodopsins/fisiologia , Feminino , Vetores Genéticos , Células HEK293 , Hipocampo/fisiologia , Humanos , Luciferases/genética , Luciferases/fisiologia , Masculino , Camundongos , Cultura Primária de Células , Ratos Sprague-Dawley , Volvox/genéticaRESUMO
Herein, we describe the fabrication and characterization of carbonized disulfide core-crosslinked polymer dots with pH-cleavable colorimetric nanosensors, based on diol dye-conjugated fluorescent polymer dots (L-PD), for reduction-triggered paclitaxel (PTX) release during fluorescence imaging-guided chemotherapy of tumors. L-PD were loaded with PTX (PTX loaded L-PD), via π-π stackings or hydrophobic interactions, for selective theragnosis by enhanced release of PTX after the cleavage of disulfide bonds by high concentration of glutathione (GSH) in a tumor. The nano-hybrid system showed fluorescence quenching behavior with less than 2% of PTX released under physiological conditions. However, in a tumor microenvironment, the fluorescence recovered at an acidic-pH, and PTX (approximately 100% of the drug release) was released efficiently out of the matrix by reduction caused by the GSH level in the tumor cells, which improved the effectiveness of the cancer treatment. Therefore, the colorimetric nanosensor showed promising potential in distinguishing between normal and cancerous tissues depending on the surrounding pH and GSH concentrations so that PTX can be selectively delivered into cancer cells for improved cancer diagnosis and chemotherapy.
Assuntos
Antineoplásicos/administração & dosagem , Nanopartículas/química , Paclitaxel/administração & dosagem , Polímeros/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Técnicas Biossensoriais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Colorimetria , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Fluorescência , Glutationa/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/ultraestrutura , Oxirredução , Paclitaxel/síntese química , Paclitaxel/química , Paclitaxel/uso terapêuticoRESUMO
The reversible volume transition of redox-responsive hydrogels by near-infrared (NIR) irradiation has recently attracted significant attention as a novel therapy matrix for tracking and treating cancer via stimuli-responsive fluorescence on/off with controllable volume transition via a wireless sensing system. Herein, a NIR-induced redox-sensitive hydrogel was synthesized by blending a hydrogel with IR825-loaded carbon dots (CD) to achieve enhanced mobility of nanoparticles inside a gel network, and reversible volume phase transitions remotely controlled by a smartphone application via the induction of different redox environments. The presence of CD-IR825 in the thermosensitive poly(N-isopropylacrylamide) hydrogel network imparted fluorescence, electronic and photothermal properties to the hydrogels, which resulted in volume shrinkage behavior of the hydrogel upon exposure to NIR laser irradiation due to the redox-sensitive CDs. Under the NIR on/off cycles, the photothermal temperature, fluorescence, and porous structure were reversed after turning off the NIR laser. The hydrogel responsiveness under GSH and NIR light was studied using a wireless device based on the changes in the resistance graph on a smartphone application, generating a fast and simple method for the investigation of hydrogel properties. The in vitro cell viabilities of the MDA-MB cancer cells incubated with the composite hydrogel in the presence of external GSH exhibited a higher photothermal temperature, and the cancer cells were effectively killed after the NIR irradiation. Therefore, the NIR-induced redox-responsive nanocomposite hydrogel prepared herein has potential for use in cancer treatment and will enable the study of nanoparticle motion in hydrogel networks under multiple stimuli via a wireless device using a faster and more convenient method.
Assuntos
Resinas Acrílicas/química , Carbono/química , Hidrogéis/química , Neoplasias/terapia , Fototerapia , Pontos Quânticos/química , Temperatura , Sobrevivência Celular , Humanos , Raios Infravermelhos , Estrutura Molecular , Oxirredução , Células Tumorais CultivadasRESUMO
A redox-responsive fluorescent carbon nanogel (FCN) was designed as a bioimaging probe for targeted drug delivery to cancer cells. FCN was synthesized by the carbonization of disulfide cross-linked hyaluronic acid in the fluorescence "on" mode, followed by the attachment of manganese oxide (MnO2) nanosheets for fluorescence quenching (fluorescence "off"). We hypothesized that the fluorescence intensity of paclitaxel (PTX)-MnO2/FCN would suddenly increase (fluorescence "on") in the presence of a high level of glutathione (GSH) in cancer cells, owing to the reduction of MnO2 to Mn2+ and cleavage of the disulfide bond. Consequently, PTX would be released from the FCN system. Consistent with this hypothesis, the designed system recovered FCN fluorescence and triggered drug release through the cleavage of the disulfide bond by GSH. Moreover, PTX-MnO2/FCN demonstrated stable fluorescence intensity after GSH treatment, serving as a potential biosensor. PTX-MnO2/FCN exhibited excellent biocompatibility with normal cells and selectively targeted tumor cells, highlighting the therapeutic capabilities of this system. The developed PTX-MnO2/FCN structure may serve as a smart drug delivery system with diagnostic and therapeutic properties, good selectivity, and compatibility, and with excellent potential for biomedical applications.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Fluorescência , Compostos de Manganês/química , Óxidos/química , Paclitaxel/administração & dosagem , Animais , Carbono/química , Linhagem Celular Tumoral/citologia , Sobrevivência Celular/efeitos dos fármacos , Cães , Liberação Controlada de Fármacos , Glutationa/farmacologia , Ácido Hialurônico/química , Células Madin Darby de Rim Canino , Nanocompostos/química , Nanopartículas , Oxirredução , Paclitaxel/farmacologia , Polímeros/químicaRESUMO
Here, we designed a pH-responsive Indocyanine Green (ICG)-loaded zwitterion fluorescent carbon dot (CD)-encapsulating mesoporous silica nanoparticle (MSN) for pH-tunable image-guided photothermal therapy. ICG was loaded into MSN(CD) via hydrophobic and electrostatic interactions between zwitterionic CDs and ICG to achieve a controlled photothermal temperature with a fluorescent "off/on" system. The porosity of the MSNs was altered after ICG loading because of intermolecular interactions between the CDs and ICG inside the MSN shell and core, which blocked the MSN pore. The acidic environment pH affected the fluorescent signals of the ICG-MSN(CD), reflecting the "off-on" characteristics of the synthesized MSN, which then induced the release of ICG from the matrices. Moreover, the photothermal conversion of ICG-MSN(CD) showed sufficient heat generation to kill cancer cells at an acidic pH with low-temperature elevation at physiological pH. ICG-MSN(CD) demonstrated good cell viability of MDA-MB-231 cells without irradiation; however, high necrosis was observed when the environment was adjusted to acidic pH and after near-infrared irradiation. These pH-responsive photothermal mesoporous silica nanoparticles may have applications in biomedicine, particularly for cancer treatment.
Assuntos
Carbono/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Raios Infravermelhos , Nanopartículas/química , Fototerapia , Dióxido de Silício/química , Transporte Biológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Temperatura Alta , Humanos , Concentração de Íons de Hidrogênio , Verde de Indocianina/química , Verde de Indocianina/metabolismo , Verde de Indocianina/farmacologia , Necrose/induzido quimicamente , Porosidade , Espécies Reativas de Oxigênio/metabolismoRESUMO
Innovative methods to detect and kill pathogenic bacteria have a pivotal role in the eradication of infectious diseases and the prevention of the growth of antibiotic-resistant bacteria. The combination of fluorescent carbon dots (FCDs) with silver nanoparticles (AgNPs) is an effective material for synergic detection and antimicrobial activity determination. However, the fluorescence quenching of the FCDs owing to an interaction with AgNP is a major limitation. In this study, we designed a system to utilize poly(vinylpyrrolidone) (PVP) and catechol chemistry (PVP@Ag:FCD) in order to avoid the fluorescence quenching of the FCD-AgNP combination due to Forster Resonance Energy Transfer (FRET). PVP@Ag:FCD exhibited bright fluorescence, which can be used for bacterial detection, through the promotion of electrostatic binding with the negatively-charged bacterial surface and generation of fluorescence quenching due to aggregation-induced quenching. Furthermore, the presence of silver nanoparticles in PVP@Ag:FCD produced an excellent bacteria killing efficiency against E. coli and S. aureus, even at low concentrations (0.1â¯mg/mL). In contaminated river water, the PVP@Ag:FCD system showed a simple, highly sensitive, and effective performance for both the detection and eradication of bacteria. Therefore, this system offers an auspicious method for the future detection and killing of bacteria.
Assuntos
Carbono/química , Nanopartículas Metálicas/química , Pontos Quânticos/química , Prata/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Catecóis/química , Sobrevivência Celular/efeitos dos fármacos , Cães , Escherichia coli/efeitos dos fármacos , Transferência Ressonante de Energia de Fluorescência , Células Madin Darby de Rim Canino , Nanopartículas Metálicas/toxicidade , Microscopia Confocal , Tamanho da Partícula , Povidona/química , Staphylococcus aureus/efeitos dos fármacos , Eletricidade Estática , Purificação da Água/métodosRESUMO
Purpose: The overlap method is one of the most popular procedures for construction of an esophagojejunostomy and its common entry is usually closed with sutures. This study aimed to report long-term complications and surgical outcomes of the overlap method with stapled closure (OMSC), to compare them with those of laparoscopy-assisted total gastrectomy (LATG), and to analyze a learning curve. Methods: Between January 2015 and August 2017, 100 consecutive patients underwent laparoscopic total gastrectomy with OMSC for gastric cancer and the patients' medical records were reviewed. Their clinicopathologic characteristics, surgical outcomes, and long-term complications were investigated and compared with those of the LATG group. A learning curve of OMSC was analyzed using the Exponentially Weighted Moving Average chart. Results: The overall duration of surgery was shorter in the LATG group; however, there was no difference in patients with early gastric cancer. Hospital admission was shorter and the pain scale was lower in the OMSC group. There was no difference in the number of harvested lymph nodes, date of flatus, or incidence of postoperative morbidity. Both groups showed no duodenal stump leakage, anastomosis-related complications, recurrence, or mortality during the follow-up period. Petersen hernia was a notable long-term event following OMSC compared with LATG. At least 27 cases of surgery were required to reach a plateau in terms of surgery duration for OMSC. Conclusion: OMSC is a safe option for the treatment of gastric cancer and has favorable long-term results and surgical outcomes. Closure of mesenteric defects and Petersen space should be considered.
RESUMO
In the present study, a pH/redox-responsive cationic polymer dot (CD) was successfully prepared for a near-infrared (NIR)-mediated, simultaneously controllable photothermal temperature guided imaging off/on system to monitor therapeutic delivery. Carbonized disulfide cross-linked branched polyethyleneimine (bPEI) was conjugated with folic acid (FA) as a targeting moiety and partially formed an ionic complex with anionic indocyanine green (ICG) to afford a bPEI-based CD (ICG-CD). This was responsive to mild reductive (glutathione, GSH) and acidic tumor conditions, which enabled the simultaneous biodegradation of those hydrophobic and complex sites. The ICG-CD internalized readily into the cytoplasm of cancer cells by a FA receptor and cationic-mediated endocytosis in the off state, whereas if ICG-CD met intracellular GSH at high concentrations, GSH contributed partially to the recovery of fluorescence and was then internalized into acidic endosomes to induce complete restoration of fluorescence. This tumor-sensitive degradability of the CD not only facilitated ICG release in the tumor location but also allowed controllable photothermal therapy effects of nanoparticles under NIR irradiation, which resulted in improved cancer therapy. Taken together, the results indicate great potential in tumor targeting, intracellular imaging, and controllable therapeutic delivery through a fluorescence off/on assay under the pH/redox conditions of cancer cells.
Assuntos
Antineoplásicos/farmacologia , Corantes Fluorescentes/farmacologia , Verde de Indocianina/farmacologia , Pontos Quânticos/química , Animais , Antineoplásicos/química , Carbono/química , Linhagem Celular Tumoral , Cães , Endocitose/fisiologia , Endossomos/metabolismo , Fluorescência , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Receptores de Folato com Âncoras de GPI/metabolismo , Ácido Fólico/química , Ácido Fólico/metabolismo , Glutationa/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Hipertermia Induzida/métodos , Verde de Indocianina/química , Verde de Indocianina/metabolismo , Raios Infravermelhos , Células Madin Darby de Rim Canino , Oxirredução , Fototerapia/métodos , Polietilenoglicóis/química , Polietilenoglicóis/metabolismo , Polietilenoimina/química , Polietilenoimina/metabolismo , Pontos Quânticos/efeitos da radiação , Nanomedicina Teranóstica/métodosRESUMO
Redox-responsive polymer dot (PD) were synthesized from disulfide cross-linked polymers in a carbonized process to allow quenching effects by loading of boron-dipyrromethene (BODIPY) onto the matrix. The disulfide linkage facilitated degradation of the PD system by intracellular glutathione (GSH), leading to fluorescence recovery by BODIPY and intracellular drug release. The paclitaxel release profile showed that approximately 100% of the drug escaped from the matrix in response to 10â¯mM GSH, whereas less than 10% was released in the absence of GSH. In vitro studies showed that quenching produced by BODIPY loading enabled visual monitoring of cancer cell death, as the quenching disappeared when BODIPY was released by GSH inside of cancer cells. The PD contain disulfide bonds representing a GSH-triggered ligand; thus, nanocarriers presented enhanced in vivo chemotherapeutic inhibition in xenograft tumor-bearing mice localized at the cancer location, guided by fluorescent off-on system tracking and measured by the release of BODIPY. This platform reacts to the redox level in sensitive manner and cancer cell death can be monitored by fluorescence, making this platform useful for bio-applications, particularly in vitro and in vivo therapy and diagnosis, while considering the cell physiological environment. This system may be useful for wider medical applications.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias/tratamento farmacológico , Paclitaxel/administração & dosagem , Polímeros/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Compostos de Boro/química , Linhagem Celular Tumoral , Cães , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Transferência Ressonante de Energia de Fluorescência/métodos , Glutationa/metabolismo , Humanos , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Oxirredução , Paclitaxel/química , Paclitaxel/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Herein we describe fluorescence resonance energy transfer (FRET) for a pH/redox-activatable fluorescent carbon dot (FNP) to realize "off-on" switched imaging-guided controllable photothermal therapy (PTT). The FNP is a carbonized self-crosslinked polymer that allows IR825 loading (FNP[IR825]) via hydrophobic interactions for cancer therapy. Fluorescence bioimaging was achieved by the internalization of FNP(IR825) into tumor cells, wherein glutathione (GSH) disulfide bonds are reduced, and benzoic imine groups are cleaved under acidic conditions. The release of IR825 from the FNP core in this system may be used to efficiently control PTT-mediated cancer therapy via its photothermal conversion after near-infrared (NIR) irradiation. In vitro and in vivo cellular uptake studies revealed efficient uptake of FNP(IR825) by tumor cells to treat the disease site. In this way we demonstrated in mice that our smart nanocarrier can effectively kill tumor cells under exposure to a NIR laser, and that the particles are biocompatible with various organs. This platform responds sensitively to the exogenous environment inside the cancer cells and may selectively induce the release of PTT-mediated cytotoxicity. Furthermore, this platform may be useful for monitoring the elimination of cancer cells through the fluorescence on/off switch, which can be used for various applications in the field of cancer cell therapy and diagnosis.
Assuntos
Benzoatos/uso terapêutico , Corantes/uso terapêutico , Preparações de Ação Retardada/química , Indóis/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Pontos Quânticos/química , Animais , Benzoatos/administração & dosagem , Carbono/química , Linhagem Celular Tumoral , Corantes/administração & dosagem , Cães , Feminino , Transferência Ressonante de Energia de Fluorescência/métodos , Humanos , Concentração de Íons de Hidrogênio , Hipertermia Induzida/métodos , Indóis/administração & dosagem , Raios Infravermelhos , Células Madin Darby de Rim Canino , Camundongos Endogâmicos BALB C , Camundongos Nus , Imagem Óptica/métodos , Oxirredução , Fototerapia/métodosRESUMO
We developed nanoparticles comprising a photothermal dye (IR825)-loaded carbonized zwitterionic polymer [FNP-I] as "switch-on" pH-responsive fluorescence probes to sense intracellular cancer cells and for near-infrared (NIR) controllable photothermal therapy (PTT) in vivo and in vitro. The fluorescent "off" of FNP-I was activated after reaching the cancer cell environment, where the zwitterionic compartment of FNP lost its hydrophobicity to induce PTT-mediated heat release of IR825 under NIR irradiation in the tumor. Approximately 100% of the IR825 was released from the FNP core to generate high thermal conversion to completely kill the cancer cells. Furthermore, after intravenous treatment of FNP-I into MDAMB-231-cell bearing mice, pH-responsive photothermal therapy was observed, achieving marked ablation of tumor cells with release of IR825 under tumor environment conditions. In addition, fluorescent signals were clearly found at the tumor site after 3 h, decreasing at the 6 h time point. The in vitro and in vivo detection system demonstrated good cellular uptake and biocompatibility as a potential imaging-guided photothermal therapy nanotool for cancer treatment. Interestingly, the synergism of the biosensor and PTT in single FNP-I platform led to more effective cancer cell killing than either monotherapy, providing a new approach for cancer treatment.
Assuntos
Carbono/química , Fluorescência , Nanopartículas/química , Neoplasias/terapia , Nanomedicina Teranóstica , Animais , Benzoatos , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Hipertermia Induzida , Indóis , Raios Infravermelhos , CamundongosRESUMO
A specific membrane and nucleus targeted fluorescence OFF-ON-OFF system, using the dodecane/sulfobetaine group of functionalized carbon dots (CD) with a copper ion (Cu2+-CD) based on the presence of pyrophosphate (PPi) molecules and alkaline phosphatase (ALP) activity, for cancer cell detection was designed. The biosensor could be effectively transported from the cytosol to the nucleus in MDAMB cells, but not in MDCK cells due to the response to a change in pH by CD functionalized with zwitterionic groups. The biosensor also showed a membrane-selective regulated route for fusion of long alkyl chain grafted-CD on cell membranes. As a potential sensor, the fluorescence of the prepared Cu2+-CD was significantly quenched due to aggregation. In human cancer MDAMB cells, a nearly complete restoration of the fluorescence intensity of the Cu2+-CD was observed because of the high levels of intracellular PPi, which preferentially bound to Cu2+. After 10 min, in the MDAMB cells, re-quenching of the CD fluorescence occurred because of the high level of intracellular ALP, which can hydrolyze PPi and release the Cu2+ to re-aggregate the CD. In contrast to MDAMB cells, MDCK cells did not show an obvious response to the specific intracellular biomolecules, thus, enabling the biosensor to be used to distinguish between cancer and normal cells. In conclusion, this biosensor has the potential to be a simple and sensitive cancer diagnostic tool that can differentiate normal cells from cancer cells on coated surfaces and in aqueous states.
RESUMO
The tumor-specific sensitive fluorescence sensing of cellular alkaline phosphatase (ALP) activity on the basis of host-guest specific and pH sensitivity was conducted on coated surfaces and aqueous states. Cross-linked fluorescent nanoparticles (C-FNP) consisting of ß-cyclodextrin (ß-CD)/boronic acid (BA) and fluorescent hyaluronic acid [FNP(HA)] were conjugated to fluorescent polydopamine [FNP(pDA)]. To determine the quenching effect of this system, hydrolysis of 4-nitrophenyl phosphate (NPP) to 4-nitrophenol (NP) was performed in the cavity of ß-CD in the presence of ALP activated photoinduced electron transfer (PET) between NP and C-FNP. At an ALP level of 30-1000 U/L, NP caused off-emission of C-FNP because of their specific host-guest recognition. Fluorescence can be recovered under pH shock due to cleavage of the diol bond between ß-CD and BA, resulting in release of NP from the fluorescent system. Sensitivity of the assays was assessed by confocal imaging not only in aqueous states, but also for the first time on coated surfaces in MDAMB-231 and MDCK cells. This novel system demonstrated high sensitivity to ALP through generation of good electron donor/acceptor pair during the PET process. Therefore, this fluorescence sensor system can be used to enhance ALP monitoring and cancer diagnosis on both coated surfaces and in aqueous states in clinical settings.
Assuntos
Fosfatase Alcalina/metabolismo , Carbono/química , Reagentes de Ligações Cruzadas/química , Corantes Fluorescentes/química , Indóis/química , Nanopartículas/química , Polímeros/química , Animais , Linhagem Celular Tumoral , Cães , Fluorescência , Humanos , Concentração de Íons de Hidrogênio , Células Madin Darby de Rim Canino , Nitrofenóis/química , Nitrofenóis/metabolismo , Compostos Organofosforados/química , Compostos Organofosforados/metabolismo , Tamanho da Partícula , Soluções , Propriedades de Superfície , Água/química , beta-Ciclodextrinas/química , beta-Ciclodextrinas/metabolismoRESUMO
The ability to quickly detect and kill bacteria is crucial in the realm of antibiotic resistance. In this study, we synthesized a detection probe consisting of polyethylenimine (PEI)-passivated polydopamine-based fluorescent carbon (FDA:PEI) nanoparticles, generating a cationic adhesive material for bacterial detection that is surface-coatable, photothermal, and antibacterial. The cationic FDA:PEI nanoparticles effectively bound to the anionic bacterial cell wall, resulting in a dramatic quenching effect visible in fluorescence spectra and confocal images. In this fluorescence on/off system, FDA:PEI nanoparticles showed similar bacterial detection abilities between aqueous- and solid-phase assays. Scanning electron microscopy clearly showed the attachment of FDA:PEI nanoparticles to the surface of bacteria, both in solution and as a coating on the surface of a polypropylene film. In addition to detection, this versatile material was found to have an antibacterial potential, via near-infrared irradiation to induce a heat release, killing bacteria by thermolysis. Thus, by exploiting the cationic and catechol moieties on the surface of polydopamine carbon dots, we developed a novel bacterial-detection platform that can be used in a broad range of conditions.