ABSTRACT
Monitoring pharmaceutical drugs in various mediums is crucial to mitigate adverse effects. This study presents a chemical sensor using an oval-like zinc oxide (ZnO) nanostructure for electrochemical detection of nalbuphine. The ZnO nanostructure, produced via an efficient sol-gel technique, was extensively characterized using field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), UV-visible spectrophotometry, and fourier transform infrared spectroscopy (FTIR). A slurry of the ZnO nanostructure in a binder was applied to a glassy carbon electrode (GCE). The sensor's responsiveness to nalbuphine was assessed using linear sweep voltammetry (LSV), achieving optimal performance by fine-tuning the pH. The sensor demonstrated a proportional response to nalbuphine concentrations up to 150.0 nM with a good regression coefficient (R2) and a detection limit of 6.20 nM (S/N ratio of 3). Selectivity was validated against various interfering substances, and efficacy was confirmed through real sample analysis, highlighting the sensor's successful application for nalbuphine detection.
Subject(s)
Electrochemical Techniques , Electrodes , Nalbuphine , Nanostructures , Zinc Oxide , Zinc Oxide/chemistry , Nalbuphine/analysis , Electrochemical Techniques/methods , Nanostructures/chemistry , Limit of DetectionABSTRACT
The strategic integration of multi-functionalities within a singular nanoplatform has received growing attention for enhancing treatment efficacy, particularly in chemo-photothermal therapy. This study introduces a comprehensive concept of Janus nanoparticles (JNPs) composed of Au and Fe3O4 nanostructures intricately bonded with ß-cyclodextrins (ß-CD) to encapsulate 5-Fluorouracil (5-FU) and Ibuprofen (IBU). This strategic structure is engineered to exploit the synergistic effects of chemo-photothermal therapy, underscored by their exceptional biocompatibility and photothermal conversion efficiency (â¼32.88 %). Furthermore, these ß-CD-conjugated JNPs enhance photodynamic therapy by generating singlet oxygen (1O2) species, offering a multi-modality approach to cancer eradication. Computer simulation results were in good agreement with in vitro and in vivo assays. Through these studies, we were able to prove the improved tumor ablation ability of the drug-loaded ß-CD-conjugated JNPs, without inducing adverse effects in tumor-bearing nude mice. The findings underscore a formidable tumor ablation potency of ß-CD-conjugated Au-Fe3O4 JNPs, heralding a new era in achieving nuanced, highly effective, and side-effect-free cancer treatment modalities. STATEMENT OF SIGNIFICANCE: The emergence of multifunctional nanoparticles marks a pivotal stride in cancer therapy research. This investigation unveils Janus nanoparticles (JNPs) amalgamating gold (Au), iron oxide (Fe3O4), and ß-cyclodextrins (ß-CD), encapsulating 5-Fluorouracil (5-FU) and Ibuprofen (IBU) for synergistic chemo-photothermal therapy. Demonstrating both biocompatibility and potent photothermal properties (â¼32.88 %), these JNPs present a promising avenue for cancer treatment. Noteworthy is their heightened photodynamic efficiency and remarkable tumor ablation capabilities observed in vitro and in vivo, devoid of adverse effects. Furthermore, computational simulations validate their interactions with cancer cells, bolstering their utility as an emerging therapeutic modality. This endeavor pioneers a secure and efficacious strategy for cancer therapy, underscoring the significance of ß-CD-conjugated Au-Fe3O4 JNPs as innovative nanoplatforms with profound implications for the advancement of cancer therapy.
Subject(s)
Gold , Mice, Nude , beta-Cyclodextrins , Animals , Gold/chemistry , Gold/pharmacology , beta-Cyclodextrins/chemistry , Humans , Mice , Fluorouracil/pharmacology , Fluorouracil/chemistry , Ibuprofen/pharmacology , Ibuprofen/chemistry , Photothermal Therapy , Cell Line, Tumor , Photochemotherapy/methods , Mice, Inbred BALB C , Ferric Compounds/chemistry , Ferric Compounds/pharmacologyABSTRACT
The control of human-machine interfaces (HMIs), such as motorized wheelchairs, has been widely investigated using biopotentials produced by electrochemical processes in the human body. However, many studies in this field sometimes overlook crucial factors like special users' needs, who often have inadequate muscle mass and strength, and paresis needed to operate a wheelchair. This study proposes a novel solution: an economical, universally compatible, and user-centric manual-to-powered wheelchair conversion kit. The powered wheelchair is operated using a hybrid control system integrating electroencephalogram (EEG) and electromyography (EMG), utilizing an LSTM network. It uses a low-cost electroencephalogram (EEG) headset and a wearable electromyography (EMG) electrode armband to solve these constraints. The proposed system comprised three crucial objectives: the development of an EEG-based user attentive detection system, an EMG-based navigation system, and a transform conventional wheelchair into a powered wheelchair. Human test subjects were utilized to evaluate the proposed system, and the study complied with accepted ethical guidelines. We selected four EEG features (p < 0.023) for the attentive detection system and six EMG features (p < 0.037) to detect navigation intentions. User attentive detection was achieved at 83.33 (±0.34) %, while the navigation intention system produced 86.67 (±0.52) % accuracy. The overall system was successful in reaching an accuracy rate of 85.0 (±0.19) % and a weighted average precision of 0.89. After the dataset was trained using an LSTM network, the overall accuracy produced was 97.3 (±0.5) %, higher than the accuracy produced by the Quadratic SVM classifier. By giving older and disabled people a more convenient way to use powered wheelchairs, this research helps to build ergonomic and cost-effective biopotential-based HMIs, enhancing their quality of life.
ABSTRACT
Nitrite monitoring serves as a fundamental practice for protecting public health, preserving environmental quality, ensuring food safety, maintaining industrial safety standards, and optimizing agricultural practices. Although many nitrite sensing methods have been recently developed, the quantification of nitrite remains challenging due to sensitivity and selectivity limitations. In this context, we present the fabrication of enzymeless iron oxide nanoparticle-modified zinc oxide nanorod (α-Fe2O3-ZnO NR) hybrid nanostructure-based nitrite sensor fabrication. The α-Fe2O3-ZnO NR hybrid nanostructure was synthesized using a two-step hydrothermal method and characterized in detail utilizing x-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). These analyses confirm the successful synthesis of an α-Fe2O3-ZnO NR hybrid nanostructure, highlighting its morphology, purity, crystallinity, and elemental constituents. The α-Fe2O3-ZnO NR hybrid nanostructure was used to modify the SPCE (screen-printed carbon electrode) for enzymeless nitrite sensor fabrication. The voltammetric methods (i.e., cyclic voltammetry (CV) and differential pulse voltammetry (DPV)) were employed to explore the electrochemical characteristics of α-Fe2O3-ZnO NR/SPCE sensors for nitrite. Upon examination of the sensor's electrochemical behavior across a range of nitrite concentrations (0 to 500 µM), it is evident that the α-Fe2O3-ZnO NR hybrid nanostructure shows an increased response with increasing nitrite concentration. The sensor demonstrates a linear response to nitrite concentrations up to 400 µM, a remarkable sensitivity of 18.10 µA µM-1 cm-2, and a notably low detection threshold of 0.16 µM. Furthermore, its exceptional selectivity, stability, and reproducibility make it an ideal tool for accurately measuring nitrite levels in serum, yielding reliable outcomes. This advancement heralds a significant step forward in the field of environmental monitoring, offering a potent solution for the precise assessment of nitrite pollution.
ABSTRACT
Speech impairments often emerge as one of the primary indicators of Parkinson's disease (PD), albeit not readily apparent in its early stages. While previous studies focused predominantly on binary PD detection, this research explored the use of deep learning models to automatically classify sustained vowel recordings into healthy controls, mild PD, or severe PD based on motor symptom severity scores. Popular convolutional neural network (CNN) architectures, VGG and ResNet, as well as vision transformers, Swin, were fine-tuned on log mel spectrogram image representations of the segmented voice data. Furthermore, the research investigated the effects of audio segment lengths and specific vowel sounds on the performance of these models. The findings indicated that implementing longer segments yielded better performance. The models showed strong capability in distinguishing PD from healthy subjects, achieving over 95% precision. However, reliably discriminating between mild and severe PD cases remained challenging. The VGG16 achieved the best overall classification performance with 91.8% accuracy and the largest area under the ROC curve. Furthermore, focusing analysis on the vowel /u/ could further improve accuracy to 96%. Applying visualization techniques like Grad-CAM also highlighted how CNN models focused on localized spectrogram regions while transformers attended to more widespread patterns. Overall, this work showed the potential of deep learning for non-invasive screening and monitoring of PD progression from voice recordings, but larger multi-class labeled datasets are needed to further improve severity classification.
ABSTRACT
Infectious diseases remain among the most pressing concerns for human health. This issue has grown even more complex with the emergence of multidrug-resistant (MDR) bacteria. To address bacterial infections, nanoparticles have emerged as a promising avenue, offering the potential to target bacteria at multiple levels and effectively eliminate them. In this study, silver nanoparticles (AA-AgNPs) were synthesized using the leaf extract of a medicinal plant, Abroma augusta. The synthesis method is straightforward, safe, cost-effective, and environment friendly, utilizing the leaf extract of this Ayurvedic herb. The UV-vis absorbance peak at 424 nm indicated the formation of AA-AgNPs, with the involvement of numerous functional groups in the synthesis and stabilization of the particles. AA-AgNPs exhibited robust antibacterial and antibiofilm activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). The MIC values of AA-AgNPs ranged from 8 to 32 µg/mL. Electron microscopic examination of the interaction of AA-AgNPs with the test bacterial pathogens showed a deleterious impact on bacterial morphology, resulting from membrane rupture and leakage of intracellular components. AA-AgNPs also demonstrated a dose-dependent effect in curtailing biofilm formation below inhibitory doses. Overall, this study highlights the potential of AA-AgNPs in the successful inhibition of both the growth and biofilms of MRSA and VRE bacteria. Following studies on toxicity and dose optimization, such AgNPs could be developed into effective medical remedies against infections.
ABSTRACT
OBJECTIVES: Malignant biliary stricture is a ductal narrowing of the bile duct that is often diagnosed at an advanced stage, leading to difficulty in resection. The current study aims to evaluate the feasibility of endobiliary laser treatment by quantifying the extent of coagulative necrosis in tissue under various conditions. METHODS: Ex vivo and in vivo porcine bile tissues were used for endobiliary laser treatment to characterize the dosimetric responses of the tissue to various treatment conditions: power level, irradiation time, and number of treatments. 532 nm laser light was coupled with a balloon-integrated diffusing applicator (BDA) to deliver the laser light endoscopically for tissue coagulation. The coagulated regions (maximum length and depth) in the treated tissues were evaluated histologically for quantitative comparison. RESULTS: Dosimetric evaluations with ex vivo liver tissue confirmed that both maximum length and depth of coagulative necrosis (CN) increased with applied power and number of treatments. Ex vivo bile duct tests demonstrated that BDA-assisted laser treatment at 10 W for 12 s reproducibly yielded CN with a length of 5.8 ± 1.6 mm and a depth of 0.6 ± 0.2 mm. In vivo tests presented that endoscopic laser treatment using the BDA created CN on the ductal surface without any perforation. Microscopic examinations revealed that a dense inflammatory cell infiltration and eosinophilic area in the in vivo treated tissue. The extent of CN in the in vivo tissue was 40% longer and 120% deeper (length: 8.1 ± 0.7 mm; depth: 1.3 ± 0.2 mm), compared to that in the ex vivo tissue. CONCLUSION: BDA-assisted laser treatment could be a feasible option for endoscopic treatment of biliary stricture with uniform ablation at the circumference of bile duct. Further in vivo studies will be performed in a large number of stricture-developed porcine models to examine both efficacy and safety of the proposed endobiliary laser treatment for clinical translations.
Subject(s)
Cholestasis , Swine , Animals , Constriction, Pathologic/pathology , Constriction, Pathologic/surgery , Cholestasis/etiology , Cholestasis/surgery , Bile Ducts/surgery , Bile Ducts/pathology , Lasers , Necrosis/pathologyABSTRACT
Accurate classification of cancer images plays a crucial role in diagnosis and treatment planning. Deep learning (DL) models have shown promise in achieving high accuracy, but their performance can be influenced by variations in Hematoxylin and Eosin (H&E) staining techniques. In this study, we investigate the impact of H&E stain normalization on the performance of DL models in cancer image classification. We evaluate the performance of VGG19, VGG16, ResNet50, MobileNet, Xception, and InceptionV3 on a dataset of H&E-stained cancer images. Our findings reveal that while VGG16 exhibits strong performance, VGG19 and ResNet50 demonstrate limitations in this context. Notably, stain normalization techniques significantly improve the performance of less complex models such as MobileNet and Xception. These models emerge as competitive alternatives with lower computational complexity and resource requirements and high computational efficiency. The results highlight the importance of optimizing less complex models through stain normalization to achieve accurate and reliable cancer image classification. This research holds tremendous potential for advancing the development of computationally efficient cancer classification systems, ultimately benefiting cancer diagnosis and treatment.
ABSTRACT
Temperature sensors, such as Fiber Bragg Grating (FBG) and thermocouple (TC), have been widely used for monitoring the interstitial tissue temperature during laser irradiation. The aim of the current study was to compare the performance of both FBG and TC in real-time temperature monitoring during endoscopic and circumferential laser treatment on tubular tissue structure. A 600-µm core-diameter diffusing applicator was employed to deliver 980-nm laser light (30 W for 90 s) circumferentially for quantitative evaluation. The tip of the TC was covered with a white tube (W-TC) in order to prevent direct light absorption and to minimize temperature overestimation. The temperature measurements in air demonstrated that the measurement difference in the temperature elevations was around 3.5 °C between FBG and W-TC. Ex vivo porcine liver tests confirmed that the measurement difference became lower (less than 1 °C). Ex vivo porcine esophageal tissue using a balloon-integrated catheter exhibited that both FBG and W-TC consistently showed a comparable trend of temperature measurements during laser irradiation (~2 °C). The current study demonstrated that the white tube-covered TC could be a feasible sensor to monitor interstitial tissue temperature with minimal overestimation during endoscopic laser irradiation. Further in vivo studies on gastroesophageal reflux disease will investigate the performance of the W-TC to monitor the temperature of the esophageal mucosa surface in real-time mode to warrant the safety of endoscopic laser treatment.
Subject(s)
Hyperthermia, Induced , Swine , Animals , Temperature , Lasers , Light , Optical FibersABSTRACT
The current study aims to demonstrate the feasibility of a novel balloon-integrated optical catheter (BIOC) to achieve endoscopic laser application for circumferential coagulation of a tubular tissue structure. Both optical and thermal numerical simulations were developed to predict the propagation of laser light and a spatio-temporal distribution of temperature in tissue. Ex vivo esophagus tissue was tested with 980 nm laser light at 30 W for 90 s for quantitative evaluations. In vivo porcine models were used to validate the performance of BIOC for circumferential and endoscopic laser coagulation of esophagus in terms of acute tissue responses post-irradiation. Optical simulations confirmed that a diffusing applicator was able to generate a circumferential light distribution in a tubular tissue structure. Both numerical and experimental results presented that the maximum temperature elevation occurred at 3-5 mm (muscle layer) below the mucosa surface after 90 s irradiation. In vivo tests confirmed the circumferential delivery of laser light to a deep muscle layer as well as no evidence of thermal damage to the esophageal mucosa. The proposed BIOC can be a feasible optical device to provide circumferential laser irradiation as well as endoscopic coagulation of tubular esophagus tissue for clinical applications.
Subject(s)
Laser Therapy , Lasers , Swine , Animals , Light , Endoscopy , CathetersABSTRACT
The clinical use of urethral stents is usually complicated by various adverse effects, including dysuria, fever, and urinary tract infection (UTI). Biofilms (formed by bacteria, such as Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) adhering to the stent cause UTIs in stented patients (approximately 11%). The undesirable consequences of antibiotics use include bacterial resistance, weight gain, and type 1 diabetes, which occur when antibiotics are used for a long time. We aimed to assess the efficacy of a new optical treatment with a 405 nm laser to inhibit bacterial growth in a urethral stent in vitro. The urethral stent was grown in S. aureus broth media for three days to induce biofilm formation under dynamic conditions. Various irradiation times with the 405 nm laser light were tested (5, 10, and 15 min). The efficacy of the optical treatment on biofilms was evaluated quantitatively and qualitatively. The production of reactive oxygen species helped eliminate the biofilm over the urethral stent after 405 nm irradiation. The inhibition rate corresponded to a 2.2 log reduction of colony-forming units/mL of bacteria after 0.3 W/cm2 of irradiation for 10 min. The treated stent showed a significant reduction in biofilm formation compared with the untreated stent, as demonstrated by SYTO 9 and propidium iodide staining. MTT assays using the CCD-986sk cell line revealed no toxicity after 10 min of irradiation. We conclude that optical treatment with 405 nm laser light inhibits bacterial growth in urethral stents with no or minimal toxicity.
Subject(s)
Staphylococcus aureus , Urinary Tract Infections , Humans , Anti-Bacterial Agents/pharmacology , Biofilms , Light , Stents/adverse effects , Escherichia coli , Pseudomonas aeruginosaABSTRACT
Monitoring the vital signs and physiological responses of the human body in daily activities is particularly useful for the early diagnosis and prevention of cardiovascular diseases. Here, we proposed a wireless and flexible biosensor patch for continuous and longitudinal monitoring of different physiological signals, including body temperature, blood pressure (BP), and electrocardiography. Moreover, these modalities for tracking body movement and GPS locations for emergency rescue have been included in biosensor devices. We optimized the flexible patch design with high mechanical stretchability and compatibility that can provide reliable and long-term attachment to the curved skin surface. Regarding smart healthcare applications, this research presents an Internet of Things-connected healthcare platform consisting of a smartphone application, website service, database server, and mobile gateway. The IoT platform has the potential to reduce the demand for medical resources and enhance the quality of healthcare services. To further address the advances in non-invasive continuous BP monitoring, an optimized deep learning architecture with one-channel electrocardiogram signals is introduced. The performance of the BP estimation model was verified using an independent dataset; this experimental result satisfied the Association for the Advancement of Medical Instrumentation, and the British Hypertension Society standards for BP monitoring devices. The experimental results demonstrated the practical application of the wireless and flexible biosensor patch for continuous physiological signal monitoring with Internet of Medical Things-connected healthcare applications.
Subject(s)
Biosensing Techniques , Wearable Electronic Devices , Blood Pressure , Humans , Internet , Monitoring, PhysiologicABSTRACT
The popularity of light/energy devices for cosmetic purposes (e.g., skin care) is increasing. However, the effects and underlying mechanisms remain poorly understood. Commencing in the 1960s, various studies have evaluated the beneficial effects of a light source on cells and tissues. The techniques evaluated include low-level light (laser) therapy and photobiomodulation (PBM). Most studies on PBM used red light sources, but, recently, many studies have employed near-infrared light sources including those of wavelength 800 nm. Here, we used a light-emitting diode (LED) array with a wavelength of 863 nm to treat DMBA/TPA-induced mouse skin tumors; treatment with the array delayed tumor development and reduced the levels of systemic inflammatory cytokines. These results suggest that light therapy could be beneficial. However, the effects were small. Further studies on different skin tumors using an optimized LED setup are required. Combination therapies (conventional methods and an LED array) may be useful.
Subject(s)
Low-Level Light Therapy , Skin Neoplasms , Animals , Cytokines , Infrared Rays , Low-Level Light Therapy/methods , Mice , Mice, Inbred ICR , Skin Neoplasms/chemically inducedABSTRACT
To prolong blood circulation and avoid the triggering of immune responses, nanoparticles in the bloodstream require conjugation with polyethylene glycol (PEG). However, PEGylation hinders the interaction between the nanoparticles and the tumor cells and therefore limits the applications of PEGylated nanoparticles for therapeutic drug delivery. To overcome this limitation, zwitterionic materials can be used to enhance the systemic blood circulation and tumor-specific delivery of hydrophobic agents such as IR-780 iodide dye for photothermal therapy. Herein, we developed micellar nanoparticles using the amphiphilic homopolymer poly(12-(methacryloyloxy)dodecyl phosphorylcholine) (PCB-lipid) synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The PCB-lipid can self-assemble into micelles and encapsulate IR-780 dye (PCB-lipid-IR-780). Our results demonstrated that PCB-lipid-IR-780 nanoparticle (NP) exhibited low cytotoxicity and remarkable photothermal cytotoxicity to cervical cancer cells (TC-1) upon near-infrared (NIR) laser irradiation. The biodistribution of PCB-lipid-IR-780 showed higher accumulation of PCB-lipid-IR-780 than that of free IR-780 in the TC-1 tumor. Furthermore, following NIR laser irradiation of the tumor region, the PCB-lipid-IR-780 accumulated in the tumor facilitated enhanced tumor ablation and subsequent tumor regression in the TC-1 xenograft model. Hence, these zwitterionic polymer-lipid hybrid micellar nanoparticles show great potential for cancer theranostics and might be beneficial for clinical applications.
Subject(s)
Hyperthermia, Induced/methods , Indoles/chemistry , Phototherapy/methods , Polymers/chemical synthesis , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/therapy , Animals , Cell Line, Tumor , Female , Humans , Mice , Micelles , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Polymers/chemistry , Polymers/pharmacokinetics , Tissue Distribution , Treatment Outcome , Uterine Cervical Neoplasms/metabolism , Xenograft Model Antitumor AssaysABSTRACT
Stimuli-responsive polymeric nanoparticles are useful for overcoming challenges such as transfection efficiency and the specific and safe delivery of genes to cancer cells. Transfection outcomes can be improved through spatially and temporally controlled gene release. We formulated a nanoassembly comprising a disulfide-crosslinked polyethylenimine (ssPEI) conjugated with a tumor-specific cell-penetrating peptide (DS 4-3) (SPD) polyplex and bovine serum albumin (BSA)-loaded IR780 (BI) nanoparticle, thereby forming a dual-stimulus-triggered, tumor-penetrating and gene-carrying nanoassembly (BI-SPD) via electrostatic complexing. BI-SPD nanoassembly were composed of highly stable nanosized complexes with an average size of 457⯱â¯27.5â¯nm, exhibiting an up to two-fold enhanced transfection efficiency with no sign of potential cytotoxicity in breast cancer cells. Moreover, upon laser irradiation, a four-fold increase in transfection efficiency was achieved due to the rapid endosomal escape of polyplexes triggered by the local heat induced by the BI-SPD nanoassembly. Additionally, the high redox environment in tumor cells facilitated the disassembly of the SPD polyplex for efficient plasmid release in the cytosol. The BI-SPD nanoassembly also exhibited high penetration and enhanced photothermally triggered gene expression in the 4T1 spheroid model. This BI-SPD nanoassembly has the potential to enhance the expression of therapeutic genes in tumor models without causing significant toxicity to surrounding healthy tissues, since it has shown higher tumor targeting and accumulation in the 4T1 tumor in mice model.
Subject(s)
Cell-Penetrating Peptides/administration & dosage , DNA/administration & dosage , Nanoparticles/administration & dosage , Polyethyleneimine/administration & dosage , Serum Albumin, Bovine/administration & dosage , Animals , Cell Line, Tumor , Cell-Penetrating Peptides/pharmacokinetics , Coloring Agents/administration & dosage , Coloring Agents/pharmacokinetics , DNA/pharmacokinetics , Disulfides , Gene Transfer Techniques , Indoles/administration & dosage , Indoles/pharmacokinetics , Mammary Neoplasms, Experimental/drug therapy , Mammary Neoplasms, Experimental/genetics , Mammary Neoplasms, Experimental/metabolism , Mice, Inbred BALB C , Plasmids , Polyethyleneimine/pharmacokinetics , Serum Albumin, Bovine/pharmacokineticsABSTRACT
PURPOSE: Paclitaxel (PTX) loaded hydrophobically modified glycol chitosan (HGC) micelle is biocompatible in nature, but it requires cancer targeting ability and stimuli release property for better efficiency. To improve tumor retention and drug release characteristic of HGC-PTX nanomicelles, we conjugated cancer targeting heptamethine dye, MHI-148, which acts as an optical imaging agent, targeting moiety and also trigger on-demand drug release on application of NIR 808 nm laser. PROCEDURES: The amine group of glycol chitosan modified with hydrophobic 5ß-cholanic acid and the carboxyl group of MHI-148 were bonded by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide chemistry. Paclitaxel was loaded to MHI-HGC nanomicelle by an oil-in-water emulsion method, thereby forming MHI-HGC-PTX. RESULTS: Comparison of near infrared (NIR) dyes, MHI-148, and Flamma-774 conjugated to HGC showed higher accumulation for MHI-HGC in 4T1 tumor and 4T1 tumor spheroid. In vitro studies showed high accumulation of MHI-HGC-PTX in 4T1 and SCC7 cancer cell lines compared to NIH3T3 cell line. In vivo fluorescence imaging of the 4T1 and SCC7 tumor showed peak accumulation of MHI-HGC-PTX at day 1 and elimination from the body at day 6. MHI-HGC-PTX showed good photothermal heating ability (50.3 °C), even at a low concentration of 33 µg/ml in 1 W/cm2 808 nm laser at 1 min time point. Tumor reduction studies in BALB/c nude mice with SCC7 tumor showed marked reduction in MHI-HGC-PTX in the PTT group combined with photothermal therapy compared to MHI-HGC-PTX in the group without PTT. CONCLUSION: MHI-HGC-PTX is a cancer theranostic agent with cancer targeting and optical imaging capability. Our studies also showed that it has cancer targeting property independent of tumor type and tumor reduction property by combined photothermal and chemotherapeutic effects.
Subject(s)
Carbocyanines/chemistry , Chitosan/chemistry , Coloring Agents/chemistry , Light , Micelles , Nanoparticles/chemistry , Neoplasms/therapy , Theranostic Nanomedicine , Animals , Cell Line , Coumarins/chemistry , Humans , Hyperthermia, Induced , Mice, Inbred BALB C , Mice, Nude , Nanoparticles/ultrastructure , Neoplasms/pathology , Paclitaxel/pharmacology , Phototherapy , Spectroscopy, Near-Infrared , Thiazoles/chemistry , Tissue DistributionABSTRACT
In this study, we propose using IR 780-loaded, CD44-targeted hyaluronic acid-based micelles (HA-IR 780) for enhanced photothermal therapy (PTT) effects in tumors. Two kinds of HA-C18 micelles were synthesized from different C18 feed ratios with degree of substitution of 3% and 13% respectively. Three different IR 780 weight percentages were used for micelle formation with loading content of 4.6%, 7.9%, and 10.3% respectively. The IC50 value of HA-IR 780 in TC1 cells was 21.89µgmL-1 (32.81µM). Upon irradiation of the tumor site with an 808-nm laser (2Wcm-2) for 2min, the temperature in the tumor in the HA-IR 780-treated groups reached 49.9°C which exceeds the temperature threshold to induce irreversible tissue damage. Toxicity studies showed that HA-IR 780 does not cause any adverse effects in organs, including heart, liver, lungs, kidney and spleen, although it selectively caused cell damage in the tumor region upon laser irradiation. Therefore, the present study suggests that HA-IR 780 can cause selective cell death in tumor regions due to its enhanced tumor-targeting and photothermal capabilities.
Subject(s)
Hyaluronic Acid/chemistry , Hyperthermia, Induced , Indoles/therapeutic use , Micelles , Neoplasms/drug therapy , Phototherapy , Animals , Cell Survival/drug effects , Endocytosis/drug effects , Hyaluronan Receptors/metabolism , Indoles/pharmacology , Mice, Inbred C57BL , Neoplasms/pathology , Tissue Distribution/drug effectsABSTRACT
Near-infrared fluorescent (NIRF) imaging modality holds great promise for tumor detection and offers several advantages of bioimaging, such as high tissue penetration with less background scattering. The disadvantage of NIRF bioimaging is that it has very low spatial resolution. Thus, the combination of NIRF with magnetic resonance imaging (MRI) is a good option because MRI can provide anatomical information with a higher resolution. Heptamethine cyanine dye (MHI-148) has been reported to have tumor-targeting capability which was used here as the NIRF agent. DSPE-SPION nanoparticles were synthesized by the solvent hydration method and conjugated with MHI-148 dye to form a MRI/NIRF dual imaging probe. The size and charge of the MHI-DSPE-SPION were found to be about 84 ± 6 nm and 3.7 mV by DLS & Zeta Potential analysis. In vivo MRI of the SCC7 tumor showed an enhanced accumulation of MHI-DSPE-SPION, peaking at day 1, compared to 4 hrs with the control DSPE-SPION. An in vivo photothermal tumor reduction study was done on the SCC7 tumor of BALB/c nude mice. Tumor reduction study showed complete tumor removal after 8 days. In conclusion, MHI-DSPE-SPION can be used as a cancer theranostics material because it provides MRI-optical imaging capabilities and the photothermal therapy (PTT) effect.
Subject(s)
Carbocyanines/chemistry , Hyperthermia, Induced/methods , Metal Nanoparticles/therapeutic use , Multimodal Imaging/methods , Neoplasms, Experimental/therapy , Phototherapy/methods , Spectroscopy, Near-Infrared/methods , 3T3 Cells , Animals , Cell Line, Tumor , Ferric Compounds/chemistry , Fluorescent Dyes/chemistry , Humans , Magnetic Resonance Imaging/methods , Male , Metal Nanoparticles/chemistry , Mice , Mice, Inbred BALB C , Neoplasms, Experimental/diagnostic imagingABSTRACT
BACKGROUND AND OBJECTIVE: Artificial skin phantoms have been developed as an alternative tissue for human skin experiments due to convenient use and easy storage. However, fabricating both thin (â¼100 µm) epidermis and relatively thick dermis is often cumbersome, and most developed phantoms have hardly reflected specific human skin types. The objective of this study was to fabricate skin phantoms with 3D printing technique to emulate various human skin types (I-VI) along with the corresponding optical and mechanical properties for laser tattoo removal. STUDY DESIGN/MATERIALS AND METHODS: Both gelatin and agar powders were mixed with coffee and TiO2 particles to fabricate skin phantoms with materials properties for various skin types (I-VI). A 3D printer was employed to precisely control the thickness of each phantom for epidermis and dermis layers. A number of concentrations of the coffee and TiO2 particles were used to determine the degree of absorption and scattering effects in various skin types. The optical properties between 500 and 1,000 nm for the fabricated phantoms were measured by double-integrating spheres with an inverse adding-doubling (IAD) algorithm. Optical coherence tomography (OCT) and rheometer were also utilized to evaluate optical (absorption and reduced scattering coefficients) and mechanical properties (compression modulus) of the fabricated phantoms, respectively. RESULTS: Visible color inspections presented that the skin phantoms for types I, III, and VI similarly emulated the color space of the human skin types. The optical property measurements demonstrated that the absorption (µa) and reduced scattering (µ(s')) coefficients decreased with wavelengths. Compared to the human skin type VI, a dermis phantom represented quite equivalent values of µa and µ(s') whereas an epidermis phantom showed up to 30% lower µa but almost identical µ(s') over the wavelengths. The OCT measurements confirmed that the thicknesses of the epidermis and the dermis phantoms were measured to be 138.50 ± 0.01 µm and 0.81 ± 0.04 mm, respectively. The mechanical properties of the phantoms mixed with the agar volume of 40% yielded a compression modulus of 83.7 ± 14.8 kPa, which well corresponded to that of human forearm skin (50-95 kPa). CONCLUSION: The 3D printing technique was able to reliably fabricate the double-layered phantoms emulating a variety of skin types (I-VI) along with the comparable optical and mechanical properties. Further investigations will incorporate artificial chromophores into the fabricated skin phantoms to reliably evaluate the new therapeutic wavelengths for laser tattoo removal.
Subject(s)
Laser Therapy , Phantoms, Imaging , Printing, Three-Dimensional , Skin , Tattooing , Tomography, Optical Coherence/instrumentation , HumansABSTRACT
We have prepared polymeric micelle-encapsulating quantum dots (QDots) for delivering the optically activatable protein Killer Red (KR) as a plasmid to cancer cells. QDots absorb light at a lower wavelength and emit light at a higher wavelength in the cell cytoplasm, activating the expressed KR. Once activated, KR triggers the generation of reactive oxygen species (ROS). We prepared cadmium selenide (CdSe)/zinc sulphide (ZnS) QDots and evaluated their optical properties. Subsequently, we performed morphology studies, elemental analysis, thermogravimetric analysis (TGA), and measurements of particle size and surface charge of prepared QDots encapsulated in PHEA-g-PEG-bPEI (PPP-QDot). Cellular uptake of PPP-QDot and PPP-QDot/KR nanoparticles was confirmed using confocal microscopy, and the cellular toxicity and transfection efficiency associated with uptake of PPP-QDot/KR nanoparticles were analyzed. KR expression in normal cells and cancer cells was confirmed using confocal microscopy and Western blotting. Cellular morphologies before and after intracellular activation of KR were observed using phase contrast, fluorescence, and confocal microscopy. Cell fate after exposure to blue light-emitting diode lighting was determined using apoptosis staining and a cell proliferation assay, confirming a suppression in proliferation and a reduction in metabolic activity. We determined that ROS generation contributed to cellular damage after treatment with PPP-QDot/KR nanoparticles and blue light exposure.