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Electrolytic ablation (EA) is a burgeoning treatment for solid tumors, in which electrical energy catalyzes a chemical reaction to generate reactive species that can eradicate cancer cells. However, the application of this technique has been constrained owing to the limited spatial effectiveness and complexity of the electrode designs. Therefore, the incorporation of nanotechnology into EA is anticipated to be a significant improvement. Herein, we present a therapeutic approach based on difructose dianhydride IV-conjugated polyethylenimine-polyethylene glycol-modified gold nanorods as electric nanoantennas and nanoelectrocatalysts for EA. We demonstrate that square-wave direct current (DC) fields trigger a reaction between water molecules and chloride ions on the gold nanorod surface, generating electrolytic products including hydrogen, oxygen, and chlorine gases near the electrodes, changing the pH, and inducing cell death. These electric nanoantennas showed significant efficacy in treating colorectal cancer both in vitro and in vivo after DC treatment. These findings clearly indicate that gold nanoantennas enhance the effectiveness of EA by creating a localized electric field and catalyzing electrolytic reactions for the induction of locoregional pH changes within the tumor. By overcoming the limitations of traditional EA and offering an enhanced level of tumor specificity and control, this nanotechnology-integrated approach advances further innovations in cancer therapies.
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Phototherapies, such as photothermal therapy (PTT) and photodynamic therapy (PDT), combined with novel all-in-one light-responsive nanocomposites have recently emerged as new therapeutic modalities for the treatment of cancer. Herein, we developed novel all-in-one triphenylphosphonium-functionalized gold nanorod/zinc oxide core-shell nanocomposites (CTPP-GNR@ZnO) for mitochondrial-targeted PTT/PDT owing to their good biocompatibility, tunable and high optical absorption, photothermal conversion efficiency, highest reactive oxygen species (ROS) generation, and high mitochondrial-targeting capability. Under laser irradiation of 780 nm, the CTPP-GNR@ZnO core-shell nanocomposites effectively produced heat in addition to generating ROS to induce cell death, implying a synergistic effect of mild PTT and PDT in combating cancer. Notably, the in vitro PTT/PDT effect of CTPP-GNR@ZnO core-shell nanocomposites exhibited effective cell ablation (95%) and induced significant intracellular ROS after the 780 nm laser irradiation for 50 min, indicating that CTPP in CTPP-GNR@ZnO core-shell nanocomposites can specifically target the mitochondria of CT-26 cells, as well as generate heat and ROS to completely kill cancer cells. Overall, this light-responsive nanocomposite-based phototherapy provides a new approach for cancer synergistic therapy.
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This work aimed to prepare multifunctional aptamer-conjugated, photothermally responsive 5-fluorouracil (5fu)-loaded chitosan-bimetallic (Au/Pd) nanoparticles (APT-CS-5fu-Au/Pd NPs) for improved cytotoxicity in two cancer cell lines (PANC-1 and MDA-MD 231). The CS-5fu-Au/Pd NPs were polydispersed with a size of 34.43 ± 1.59 nm. FTIR analysis indicated the presence of CS, 5fu in CS-5fu-Au/Pd NPs. The 2 theta degrees in CS-5fu-Au/Pd NPs accounted for CS and Au/Pd. Additionally, AGE revealed the conjugation of APT in CS-5fu-Au/Pd NPs. The APT-CS-5fu-Au/Pd NPs (180 µg/mL) with NIR treatment increased the temperature to >50 °C. The optimized 5fu input was 0.075 % in CS-5fu-Au/Pd NPs, exhibiting a hydrodynamic size of 112.96 ± 17.23 nm, DEE of 64.2 ± 3.77 %, and DLE of 11.1 ± 0.65 %. A higher level of 5fu release (69.8 ± 2.78 %) was observed under pH 5.4 at 74 h. In conclusion, NIR-APT-CS-5fu-Au/Pd NPs did not cause toxicity to RBC and Egg CAM, but increased cytotoxicity in MDA-MB 231 and PANC-1 cells by triggering oxidative stress-mediated cell death.
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Quitosana , Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Fluoruracila/farmacologia , Morte CelularRESUMO
Precision diagnosis-guided efficient treatment is crucial to extending the lives of cancer patients. The integration of surface-enhanced Raman scattering (SERS) imaging and phototherapy into a single nanoplatform has been considered a more accurate diagnosis and treatment strategy for cancer nanotheranostics. Herein, we constructed a new type of mesoporous silica-layered gold nanorod core@silver shell nanostructures loaded with methylene blue (GNR@Ag@mSiO2-MB) as a multifunctional nanotheranostic agent for intracellular SERS imaging and phototherapy. The synthesized GNR@Ag@mSiO2-MB nanostructures possessed a uniform core-shell structure, strong near-infrared (NIR) absorbance, photothermal conversion efficiency (65%), dye loading ability, SERS signal, and Raman stability under phototherapy conditions. Under single 785 nm NIR laser irradiation, the intracellular GNR@Ag@mSiO2-MB nanostructures were dramatically decreased to <9%, which showed excellent photothermal and photodynamic effects toward cancer cell killing, indicating that the combination of photothermal therapy (PTT) and photodynamic therapy (PDT) of the GNR@Ag@mSiO2-MB nanostructures could greatly enhance the therapeutic efficacy of cancer cell death. GNR@Ag@mSiO2-MB nanostructures demonstrated a strong Raman signal at 450 and 502 cm-1, corresponding to the δ(C-N-C) mode, suggesting that the Raman bands of GNR@Ag@mSiO2-MB nanostructures were more efficient to detect CT-26 cell SERS imaging with high specificity. Our results indicate that GNR@Ag@mSiO2-MB nanostructures offer an excellent multifunctional nanotheranostic platform for SERS imaging and synergistic anticancer phototherapy in the future.
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Chronic Kidney Disease (CKD) which involves gradual loss of kidney function is characterized by low levels of a glycoprotein called Erythropoietin (EPO) that leads to red blood cell deficiency and anemia. Recombinant human EPO (rhEPO) injections that are administered intravenously or subcutaneously is the current gold standard for treating CKD. The rhEPO injections have very short half-lives and thus demands frequent administration with a risk of high endogenous EPO levels leading to severe side effects that could prove fatal. To this effect, this work provides a novel approach of using lamellar inorganic solids with a brucite-like structure for controlling the release of protein therapeutics such as rhEPO in injectable hydrogels. The nanoengineered injectable system was formulated by incorporating two-dimensional layered double hydroxide (LDH) clay materials with a high surface area into alginate hydrogels for sustained delivery. The inclusion of LDH in the hydrogel network not only improved the mechanical properties of the hydrogels (5-30 times that of alginate hydrogel) but also exhibited a high binding affinity to proteins without altering their bioactivity and conformation. Furthermore, the nanoengineered injectable hydrogels (INHs) demonstrated quick gelation, injectability, and excellent adhesion properties on human skin. The in vitro release test of EPO from conventional alginate hydrogels (Alg-Gel) showed 86% EPO release within 108 h while INHs showed greater control over the initial burst and released only 24% of EPO in the same incubation time. INH-based ink was successfully used for 3D printing, resulting in scaffolds with good shape fidelity and stability in cell culture media. Controlled release of EPO from INHs facilitated superior angiogenic potential in ovo (chick chorioallantoic membrane) compared to Alg-Gel. When subcutaneously implanted in albino mice, the INHs formed a stable gel in vivo without inducing any adverse effects. The results suggest that the proposed INHs in this study can be utilized as a minimally invasive injectable platform or as 3D printed patches for the delivery of protein therapeutics to facilitate tissue regeneration.
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Hidrogéis , Insuficiência Renal Crônica , Camundongos , Animais , Humanos , Hidrogéis/química , Engenharia Tecidual/métodos , Preparações de Ação Retardada/farmacologia , Alginatos/química , HidróxidosRESUMO
Novel biocompatible and efficient photothermal (PT) therapeutic materials for cancer treatment have recently garnered significant attention, owing to their effective ablation of cancer cells, minimal invasiveness, quick recovery, and minimal damage to healthy cells. In this study, we designed and developed calcium ion-doped magnesium ferrite nanoparticles (Ca2+-doped MgFe2O4 NPs) as novel and effective PT therapeutic materials for cancer treatment, owing to their good biocompatibility, biosafety, high near-infrared (NIR) absorption, easy localization, short treatment period, remote controllability, high efficiency, and high specificity. The studied Ca2+-doped MgFe2O4 NPs exhibited a uniform spherical morphology with particle sizes of 14.24 ± 1.32 nm and a strong PT conversion efficiency (30.12%), making them promising for cancer photothermal therapy (PTT). In vitro experiments showed that Ca2+-doped MgFe2O4 NPs had no significant cytotoxic effects on non-laser-irradiated MDA-MB-231 cells, confirming that Ca2+-doped MgFe2O4 NPs exhibited high biocompatibility. More interestingly, Ca2+-doped MgFe2O4 NPs exhibited superior cytotoxicity to laser-irradiated MDA-MB-231 cells, inducing significant cell death. Our study proposes novel, safe, high-efficiency, and biocompatible PT therapeutics for treating cancers, opening new vistas for the future development of cancer PTT.
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Despite the many advanced strategies that are available, rapid gene mutation in multidrug-resistant bacterial infections remains a major challenge. Combining new therapeutic strategies such as chemo-photothermal therapy (PTT) with high antibacterial efficiency against drug-resistant Listeria monocytogenes (LM) is urgently needed. Here, we report synergistic chemo-PTT against drug-resistant LM based on antibody-conjugated and streptomycin-chitosan oligosaccharide-modified gold nanoshells (anti-STR-CO-GNSs) as all-in-one nanotheranostic agents for the first time, which was used for accurate antibacterial applications. The anti-STR-CO-GNSs showed excellent photothermal conversion efficiency (31.97 %) and were responsive to near-infrared (NIR) and pH dual stimuli-triggered antibiotic release, resulting in outstanding chemo-photothermal effects against LM. In vitro chemo-photothermal effect of anti-STR-CO-GNSs with laser irradiation caused a greater antibacterial effect (1.37 %), resulting in more rapid killing of LM and prevention of LM regrowth. Most importantly, the mice receiving the anti-STR-CO-GNSs with laser irradiation specifically at the sites of LM infections healed almost completely, leaving only scars on the surface of the skin and resulting in superior inhibitory effects from combined chemo-PTT. Overall, our findings suggest that chemo-PTT using smart biocompatible anti-STR-CO-GNSs is a favorable potential alternative to combat the increasing threat of drug-resistant LM, which opens a new door for clinical anti-infection therapy in the future.
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Infecções Bacterianas , Quitosana , Hipertermia Induzida , Nanoconchas , Animais , Camundongos , Terapia Fototérmica , Fototerapia/métodos , Estreptomicina/farmacologia , Ouro/farmacologia , Hipertermia Induzida/métodos , Antibacterianos/farmacologia , OligossacarídeosRESUMO
Photo-nanotheranostics integrates near-infrared (NIR) light-triggered diagnostics and therapeutics, which are combined into a novel all-in-one phototheranostic nanomaterial that holds great promise for the early detection and precise treatment of cancer. In this study, we developed methylene blue-loaded mesoporous silica-coated gold nanorods on graphene oxide (MB-GNR@mSiO2-GO) as an all-in-one photo-nanotheranostic agent for intracellular surface-enhanced Raman scattering (SERS) imaging-guided photothermal therapy (PTT)/photodynamic therapy (PDT) for cancer. Amine functionalization of the MB-GNR@mSiO2 surfaces was performed using 3-aminopropyltriethoxysilane (APTES), which was well anchored on the carboxyl groups of graphene oxide (GO) nanosheets uniformly, and showed a remarkably higher photothermal conversion efficiency (48.93%), resulting in outstanding PTT/PDT for cancer. The in vitro photothermal/photodynamic effect of MB-GNR@mSiO2-GO with laser irradiation showed significantly reduced cell viability (6.32%), indicating that MB-GNR@mSiO2-GO with laser irradiation induced significantly more cell deaths. Under laser irradiation, MB-GNR@mSiO2-GO showed a strong SERS effect, which permits accurate cancer cell detection by SERS imaging. Subsequently, the same Raman laser can focus on highly detected MDA-MB-23l cells for a prolonged time to perform PTT/PDT. Therefore, MB-GNR@mSiO2-GO has great potential for precise SERS imaging-guided synergistic PTT/PDT for cancer.
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This work developed a pH/NIR responsive antibacterial agent (CS-FeNPs) composed of chitosan (CS) and Fe3O4 nanoparticles (FeNPs). CS triggers bacterial attraction through surface charge, while Fe acts as a photothermal agent (PTA). The CS-Fe NPs exhibited antibacterial and antibiofilm activity against both bacteria (G+/G-). However, higher activity was observed against bacteria (G-) due to electrostatic interactions. The CS-FeNPs bind with the bacterial membrane through electrostatic interactions and disturb bacterial cells. Later, in an acidic environment, CS-FeNPs bind with bacterial membrane, and NIR irradiation leads the antibacterial activity. CS-FeNPs exhibited a potential photothermal conversion efficiency (η) of 21.53 %. Thus, it converts NIR irradiation into heat to kill the bacterial pathogen. The CS-FeNPs were found to be less cytotoxic with great antibacterial efficiency on planktonic bacteria and their biofilm, which indicates that they deserve to develop potential and safe treatment strategies for the treatment of bacterial infections.
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Quitosana , Antibacterianos/farmacologia , Bactérias , Biofilmes/efeitos da radiação , Quitosana/farmacologia , Nanopartículas Magnéticas de Óxido de FerroRESUMO
In situ-gel-forming thermoresponsive copolymers have been widely exploited in controlled delivery applications because their critical gel temperature is similar to human body temperature. However, there are limitations to controlling the delivery of biologics from a hydrogel network because of the poor networking and reinforcement between the copolymer networks. This study developed an in situ-forming robust injectable and 3D printable hydrogel network based on cellulose nanocrystals (CNCs) incorporated amphiphilic copolymers, poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide (PCLA). In addition, the physicochemical and mechanical properties of injectable hydrogels were controlled by physically incorporating CNCs with amphiphilic PCLA copolymers. CNCs played an unprecedented role in physically reinforcing the PCLA copolymers' micelle network via intermicellar bridges. Apart from that, the free-flowing closely packed rod-like CNCs incorporated PCLA micelle networks at low temperature transformed to a stable viscoelastic hydrogel network at physiological temperature. CNC incorporated PCLA copolymer sols effectively coordinated with hydrophobic doxorubicin and water-soluble lysozyme by a combination of hydrophobic and hydrogen bonding interaction and controlled the release of biologics. As shown by the 3D printing results, the biocompatible PCLA hydrogels continuously extruded during printing had good injectability and maintained high shape fidelity after printing without any secondary cross-linking steps. The interlayer bonding between the printed layers was high and formed stable 3D structures up to 10 layers. Subcutaneous injection of free-flowing CNC incorporated PCLA copolymer sols to BALB/c mice formed a hydrogel instantly and showed controlled biodegradation of the hydrogel depot without induction of toxicity at the implantation sites or surrounding tissues. At the same time, the in vivo antitumor effect on the MDA-MB-231 tumor xenograft model demonstrated that DOX-loaded hydrogel formulation significantly inhibited the tumor growth. In summary, the CNC incorporated biodegradable hydrogels developed in this study exhibit a prolonged release with special release kinetics for hydrophobic and hydrophilic biologics.
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Produtos Biológicos , Neoplasias da Mama , Nanopartículas , Animais , Neoplasias da Mama/tratamento farmacológico , Celulose , Preparações de Ação Retardada/farmacologia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Humanos , Hidrogéis/química , Camundongos , Micelas , Muramidase , Nanopartículas/uso terapêutico , Poliésteres/química , Polietilenoglicóis/química , Polímeros/química , Impressão Tridimensional , Temperatura , ÁguaRESUMO
Articular cartilage injury is characterized by limited self-repair capacity due to the shortage of blood vessels, lymphatics, and nerves. Hence, this study aims to exploit a classic injectable hydrogel platform that can restore the cartilage defects with minimally invasive surgery, which is similar to the natural extracellular microenvironment, and highly porous network for cell adhesion and proliferation. In this study, an injectable scaffold system comprised of silk fibroin (SF) and hyaluronic acid (HA) was developed to adapt the above requirements. Besides, methylprednisolone (MP) was encapsulated by SF/HA scaffold for alleviating inflammation. The SF/HA hydrogel scaffold was prepared by chemical cross-linking between the lysine residues of SF via Schiff base formation, and pore diameter of the obtained hydrogels was 100.47 ± 32.09 µm. The highly porous nature of hydrogel could further benefit the soft tissue regeneration. Compared with HA-free hydrogels, SF/HA hydrogel showed more controlled release on MP. In ovo experiment of chick embryo chorioallantoic membrane (CAM) demonstrated that SF/HA hydrogels not altered the angiogenesis and formation of blood vessels, thus making it suitable for cartilage regeneration. Furthermore, in vivo gel formation was validated in mice model, suggesting in situ gel formation of SF/HA hydrogels. More importantly, SF/HA hydrogels exhibited the controlled biodegradation. Overall, SF/HA hydrogels provide further insights to the preparation of effective scaffold for tissue regeneration and pave the way to improve the articular cartilage injury treatment.
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Photothermal (PT)-enhanced Fenton-based chemodynamic therapy (CDT) has attracted a significant amount of research attention over the last five years as a highly effective, safe, and tumor-specific nanomedicine-based therapy. CDT is a new emerging nanocatalyst-based therapeutic strategy for the in situ treatment of tumors via the Fenton reaction or Fenton-like reaction, which has got fast progress in recent years because of its high specificity and activation by endogenous substances. A variety of multifunctional nanomaterials such as metal-, metal oxide-, and metal-sulfide-based nanocatalysts have been designed and constructed to trigger the in situ Fenton or Fenton-like reaction within the tumor microenvironment (TME) to generate highly cytotoxic hydroxyl radicals (â¢OH), which is highly efficient for the killing of tumor cells. However, research is still required to enhance the curative outcomes and minimize its side effects. Specifically, the therapeutic efficiency of certain CDTs is still hindered by the TME, including low levels of endogenous hydrogen peroxide (H2O2), overexpression of reduced glutathione (GSH), and low catalytic efficacy of Fenton or Fenton-like reactions (pH 5.6-6.8), which makes it difficult to completely cure cancer using monotherapy. For this reason, photothermal therapy (PTT) has been utilized in combination with CDT to enhance therapeutic efficacy. More interestingly, tumor heating during PTT not only causes damage to the tumor cells but can also accelerate the generation of â¢OH via the Fenton and Fenton-like reactions, thus enhancing the CDT efficacy, providing more effective cancer treatment when compared with monotherapy. Currently, synergistic PT-enhanced CDT using multifunctional nanomaterials with both PT and chemodynamic properties has made enormous progress in cancer theranostics. However, there has been no comprehensive review on this subject published to date. In this review, we first summarize the recent progress in PT-enhanced Fenton-based CDT for cancer treatment. We then discuss the potential and challenges in the future development of PT-enhanced Fenton-based nanocatalytic tumor therapy for clinical application.
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This study developed folic acid (FA) conjugated chitosan (CS) encapsulated rutin (R) synthesized palladium nanoclusters (Pd NCs) for NIR triggered and folate receptor (FR) targeted triple-negative breast cancer (MDA-MB 231 cells) treatment. R-Pd NCs exhibited flower-shaped particles with an average size of <100 nm. FA-CS encapsulation concealed the flower shape of R-Pd NCs with a positive charge. The XRD spectrum confirmed the cubic crystalline structure of Pd. The FA conjugation on CS improved the cellular uptake of R-Pd NCs in MDA-MB 231 cells was confirmed by TEM. FA-CS-R-Pd NCs (+NIR) treatment was considerably inhibited the MDA-MB 231 cells proliferation evidenced by cell viability, fluorescent staining, and flow cytometry analysis. Further, in vitro hemolysis assay and in Ovo model confirmed the non-toxic nature of FA-CS-R-Pd-NCs with or without NIR radiation. Hence, this study concluded that FA-CS-R-Pd NCs can be applied for the treatment of drug-resistant breast cancer.
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Antineoplásicos/administração & dosagem , Quitosana/química , Portadores de Fármacos , Ácido Fólico/química , Paládio/administração & dosagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular , Células HEK293 , Humanos , Luz , Nanopartículas/química , Rutina/química , TemperaturaRESUMO
In this study, we developed an aluminum-load-cell-based wireless Ringer's solution monitoring and alarm (WRMA) system. The Al load cell was designed with a rectangular shape, and the load was concentrated in the lower beam part of the load cell because of the anisotropic thickness. From the static analysis, we identified the appropriate location for a Wheatstone bridge circuit consisting of four strain gauges. In addition, the modal and harmonic analyses showed that the vibrational frequencies of the hospital environment do not seriously interfere with the output voltage of the Al load cell. However, random vibrations generated by the movement of the WRMA system on various surfaces severely increase the standard deviation of the measured solution weight by ± 10 g or more. Such vibrational error is too large because the average weight of Ringer's solution is 30-40 g at the time of replacing Ringer's solution. Thus, this error could be confusing for nurses and result in mistakes in the timely replacement of the Ringer's solution. However, the standard deviation of the measured weight was dramatically reduced to ± 3 g or less by using the vibration correction algorithm developed in the present study.
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PURPOSE: To develop an MRI/optical multimodal imaging probe based on dye-conjugated iron oxide/silica core/shell nanoparticle, and investigate the distance-dependent fluorescence quenching through careful control of the distance between the iron oxide core and fluorescent dyes. METHODS: Different size of core/shell nanoparticles were prepared by varying the silica shell width. PEGylation on the surface of silica shell was followed to improve the stability of particles in the physiological condition. In vitro cytotoxicity was evaluated by the MTT assay on a HeLa cell line and in vivo imaging of subcutaneous SCC7 xenografted mice was performed using MRI/optical imaging modalities. RESULTS: Diameter and ζ-potential of the nanoparticles were measured, and TEM images demonstrated the mono-disperse nature of the particles. Quenching efficiency of the dyes on the surface was nearly 100% in the smallest nanoparticle, while almost no quenching effect was observed for the largest nanoparticle. In vitro cytotoxicity showed nearly 90% cell viability at 0.15 Fe mg/mL, a comparable concentration for clinical use. The tumor area was significantly darkened after the nanoparticle injection due to the high transverse relaxivity value of the nanoparticles. Fluorescence signal was affected by the particle size due to the distance-dependent quenching/dequenching behaviour.
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Compostos Férricos/química , Corantes Fluorescentes/química , Imagem Multimodal/métodos , Nanopartículas/química , Dióxido de Silício/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste , Células HeLa , Humanos , Imageamento por Ressonância Magnética/métodos , Camundongos , Tamanho da Partícula , Polietilenoglicóis , Sais de Tetrazólio , Tiazóis , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Methylene blue-loaded gold nanorod@SiO2 (MB-GNR@SiO2) core@shell nanoparticles are synthesized for use in cancer imaging and photothermal/photodynamic dual therapy. For the preparation of GNR@SiO2 nanoparticles, we found that the silica coating rate of hexadecylcetyltrimethylammonium bromide (CTAB)-capped GNRs is much slower than that of PEGylated GNRs due to the densely coated CTAB bilayer. Encapsulated MB molecules have both monomer and dimer forms that result in an increase in the photosensitizing effect through different photochemical pathways. As a consequence of the excellent plasmonic properties of GNRs at near-infrared (NIR) light, the embedded MB molecules showed NIR light-induced SERS performance with a Raman enhancement factor of 3.0 × 10(10), which is enough for the detection of a single cancer cell. Moreover, the MB-GNR@SiO2 nanoparticles exhibit a synergistic effect of photodynamic and photothermal therapies of cancer under single-wavelength NIR laser irradiation.
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Neoplasias do Colo/tratamento farmacológico , Ouro/química , Raios Infravermelhos , Nanotubos/química , Fotoquimioterapia , Dióxido de Silício/química , Análise Espectral Raman/métodos , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Camundongos , Microscopia Eletrônica de Transmissão , Espalhamento de Radiação , Espectrofotometria UltravioletaRESUMO
The present work demonstrates that Cy5.5 conjugated Fe(3)O(4)/SiO(2) core/shell nanoparticles could allow us to control movement of human natural killer cells (NK-92MI) by an external magnetic field. Required concentration of the nanoparticles for the cell manipulation is as low as ~20 µg Fe/mL. However, the relative ratio of the nanoparticles loaded NK-92MI cells infiltrated into the target tumor site is enhanced by 17-fold by applying magnetic field and their killing activity is still maintained as same as the NK-92MI cells without the nanoparticles. This approach allows us to open alternative clinical treatment with reduced toxicity of the nanoparticles and enhanced infiltration of immunology to the target site.
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Separação Imunomagnética/métodos , Células Matadoras Naturais/efeitos da radiação , Células Matadoras Naturais/transplante , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapia , Animais , Linhagem Celular , Movimento Celular/efeitos da radiação , Campos Magnéticos , Nanopartículas de Magnetita , Ratos , Resultado do TratamentoRESUMO
A fabrication method of Cy5.5-MMP substrate and PEG conjugated iron oxide nanoparticles with thin silica coating (PCM-CS) and its potential as an 'activatable' dual imaging probe for tumor imaging is described in this report. PCM-CS showed an intensity-averaged diameter of 43.1 ± 6.3 nm by dynamic light scattering without any noticeable aggregation over 7 days. Fluorescence of Cy5.5 on the surface of nanoparticles was fully quenched and the quenching efficiency was 97.2%. PCM-CS showed protease specific fluorescence recovery in vitro caused from the specific peptide cleavage by MMP-2 and the probe displayed the sensitivity on 0.5 nM or less enzyme concentration. Tumor was successfully visualized by NIRF and MRI in vivo by intravenously injected PCM-CS. NIRF signal of tumor was gradually increased up to 12h post injection and the intensity of tumor was about 3-4 times higher than normal tissue. NIRF signal at MMP-2 inhibitor treated tumor was clearly lower than tumor without inhibitor due to the insufficient peptide cleavage. NIRF signal at excised tumor was 5-10 times stronger than other organs. Noticeable darkening in magnetic resonance image was observed at the tumor region and the image was gradually darkened at 12h post injection of PCM-CS. The maximum signal difference between tumor region and healthy muscle was 34%.
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Carbocianinas/química , Meios de Contraste/química , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/química , Metaloproteinase 2 da Matriz/metabolismo , Polietilenoglicóis/química , Espectroscopia de Luz Próxima ao Infravermelho , Animais , Carbocianinas/administração & dosagem , Linhagem Celular Tumoral , Meios de Contraste/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Neoplasias Experimentais/diagnóstico , Neoplasias Experimentais/enzimologia , Dióxido de Silício/químicaRESUMO
Three different ZnO nanoplate arrays on Si-wafer were successfully synthesized at 95 °C from ZnO nanoparticles with modified surface by citrate anion. Shape, size, density, and orientation of the resulting nanoplates were dramatically changed by the nucleus seed concentration, which was controlled through different coating processes on the substrate.