Precision-engineered metal and metal-oxide nanoparticles for biomedical imaging and healthcare applications.

The growing field of nanotechnology has witnessed numerous advancements over the past few years, particularly in the development of engineered nanoparticles. Compared with bulk materials, metal nanoparticles possess more favorable properties, such as increased chemical activity and toxicity, owing to their smaller size and larger surface area. Metal nanoparticles exhibit exceptional stability, specificity, sensitivity, and effectiveness, making them highly useful in the biomedical field. Metal nanoparticles are in high demand in biomedical nanotechnology, including Au, Ag, Pt, Cu, Zn, Co, Gd, Eu, and Er. These particles exhibit excellent physicochemical properties, including amenable functionalization, non-corrosiveness, and varying optical and electronic properties based on their size and shape. Metal nanoparticles can be modified with different targeting agents such as antibodies, liposomes, transferrin, folic acid, and carbohydrates. Thus, metal nanoparticles hold great promise for various biomedical applications such as photoacoustic imaging, magnetic resonance imaging, computed tomography (CT), photothermal, and photodynamic therapy (PDT). Despite their potential, safety considerations, and regulatory hurdles must be addressed for safe clinical applications. This review highlights advancements in metal nanoparticle surface engineering and explores their integration with emerging technologies such as bioimaging, cancer therapeutics and nanomedicine. By offering valuable insights, this comprehensive review offers a deep understanding of the potential of metal nanoparticles in biomedical research.

Wavelength-dependent photobiomodulation (PBM) for proliferation and angiogenesis of melanoma tumor in vitro and in vivo.

Photobiomodulation (PBM) has widely been used to effectively treat complications associated with cancer treatment, including oral mucositis, radiation dermatitis, and surgical wounds. However, the safety of PBM against cancer still needs to be validated as the effects of PBM on cancer cells and their mechanisms are unclear. The current study investigated the wavelength-dependent PBM effects by examining four different laser wavelengths (405, 532, 635, and 808 nm) on B16F10 melanoma tumor cells. In vitro tests showed that PBM with 808 nm promoted both proliferation and migration of B16F10 cells. In vivo results demonstrated that PBM with 808 nm significantly increased the relative tumor volume and promoted angiogenesis with overexpression of VEGF and HIF-1α. In addition, PBM induced the phosphorylation of factors closely related to cancer cell proliferation and tumor growth and upregulated the related gene expression. The current result showed that compared to the other wavelengths, 808 nm yielded a significant tumor-stimulating effect the malignant melanoma cancer. Further studies will investigate the in-depth molecular mechanism of PBM on tumor stimulation in order to warrant the safety of PBM for clinical cancer treatment.

Beta cyclodextrin conjugated AuFe3O4 Janus nanoparticles with enhanced chemo-photothermal therapy performance.

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 (∼32.88 %). 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 (∼32.88 %), 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.

Yb-Gd Codoped Hydroxyapatite as a Potential Contrast Agent for Tumor-Targeted Biomedical Applications.

Recently, various nanomaterials based on hydroxyapatite (HAp) have been developed for bioimaging applications. In particular, HAp doped with rare-earth elements has attracted significant attention, owing to its enhanced bioactivity and imaging properties. In this study, the wet precipitation method was used to synthesize HAp codoped with Yb and Gd. The synthesized Ybx-Gdx-HAp nanoparticles (NPs) were characterized via various techniques to analyze the crystal phase, functional groups, thermal characteristics, and particularly, the larger surface area. The IR783 fluorescence dye and a folic acid (FA) receptor were conjugated with the synthesized Ybx-Gdx-HAp NPs to develop an effective imaging contrast agent. The developed FA/IR783/Yb-Gd-HAp nanomaterial exhibited improved contrast, sensitivity, and tumor-specific properties, as demonstrated by using the customized LUX 4.0 fluorescence imaging system. An in vitro cytotoxicity study was performed to verify the biocompatibility of the synthesized NPs using MTT assay and fluorescence staining. Photodynamic therapy (PDT) was also applied to determine the photosensitizer properties of the synthesized Ybx-Gdx-HAp NPs. Further, reactive oxygen species generation was confirmed by Prussian blue decay and a 2',7'-dichlorofluorescin diacetate study. Moreover, MDA-MB-231 breast cancer cells were used to evaluate the efficiency of Ybx-Gdx-HAp NP-supported PDT.

Biodegradable manganese-doped hydroxyapatite antitumor adjuvant as a promising photo-therapeutic for cancer treatment.

The efficiency of a cancer therapy agent depends on its ability to eliminate tumors without endangering neighboring healthy tissues. In this present study, a novel multifunctional property enriched nanostructured system was synthesized on manganese-doped hydroxyapatite (Mn-HAp) conjugated with counter folic acid (FA) IR-783 fluorescence dye. The tailored synthesis of nano rod-shaped Mn-HAp nanoparticles with high surface area allows to conjugate FA/IR-783 dye which enhanced retention time during in vivo circulation. The drug-free Photothermal Photodynamic therapy mediated cancer treatment permits the prevention of collateral damages to non-cancerous cells. The safe HAp biomaterial matrix allows a large number of molecules on its surface due to its active different charge moieties (Ca2+/PO4 3-) without any recurrence toxicity. The doped Mn allows releasing of Mn2+ ions which triggered the production of toxic hydroxyl radicals (•OH) via Fenton or Fenton-like reactions to decompose H2O2 in the tumor sites. Herein, IR-783 and FA were selected for targeted fluorescence imaging-guided photothermal therapy. 6The PTT performance of synthesized nanostructured system shows enhanced potential with ∼60°C temperature elevation with 0.75 W∙cm-2 power irradiated within 7 min of treatment. PDT activity was also observed initially with Methylene Blue (MB) as a targeted material which shows a drastic degradation of MB and further in vitro studies with MDA-MB-231 breast cancer cell line show cytotoxicity due to the generated reactive oxygen species (ROS) effect. FA/IR-783 conjugated Mn-HAp nanoparticles (2.0 mol% Mn-HAp/FA-IR-783) show significant tumor-specific targeting and treatment efficiency while intravenously injected in (tail vain) BALB/c nude mice model without any recurrence. The synthesized nanostructured system had ample scope to be a promising Photo-Therapeutic agent for cancer treatment.

Computational analysis of drug free silver triangular nanoprism theranostic probe plasmonic behavior for in-situ tumor imaging and photothermal therapy.

INTRODUCTION: The advanced features of plasmonic nanomaterials enable initial high accuracy detection with different therapeutic intervention. Computational simulations could estimate the plasmonic heat generation with a high accuracy and could be reliably compared to experimental results. This proposed combined theoretical-experimental strategy may help researchers to better understand other nanoparticles in terms of plasmonic efficiency and usability for future nano-theranostic research. OBJECTIVES: To develop innovative computationally-driven approach to quantify any plasmonic nanoparticles photothermal efficiency and effects before their use as therapeutic agents. METHODS: This report introduces drug free plasmonic silver triangular nanoprisms coated with polyvinyl alcohol biopolymer (PVA-SNT), for in vivo photoacoustic imaging (PAI) guided photothermal treatment (PTT) of triple-negative breast cancer mouse models. The synthesized PVA-SNT nanoparticles were characterized and a computational electrodynamic analysis was performed to evaluate and predict the optical and plasmonic photothermal properties. The in vitro biocompatibility and in vivo tumor abalation study was performed with MDA-MB-231 human breast cancer cell line and in nude mice model. RESULTS: The drug free 140 µg∙mL-1 PVA-SNT nanoparticles with 1.0 W∙cm-2 laser irradiation for 7 min proved to be an effective and optimized theranostic approach in terms of PAI guided triple negative breast cancer treatment. The PVA-SNT nanoparticles exhibits excellent biosafety, photostability, and strong efficiency as PAI contrast agent to visualize tumors. Histological analysis and fluorescence-assisted cell shorter assay results post-treatment apoptotic cells, more importantly, it shows substantial damage to in vivo tumor tissues, killing almost all affected cells, with no recurrence. CONCLUSION: This is a first complete study on computational simulations to estimate the plasmonic heat generation followed by drug free plasmonic PAI guided PTT for cancer treatment. This computationally-driven theranostic approach demonstrates an innovative thought regarding the nanoparticles shape, size, concentration, and composition which could be useful for the prediction of photothermal heat generation in precise nanomedicine applications.

Fluorescence conjugated nanostructured cobalt-doped hydroxyapatite platform for imaging-guided drug delivery application.

Multifunctional nanomaterials developed from hydroxyapatite (HAp) with enhanced biological characteristics have recently attracted attention in the biomedical field. The goal of this study is to investigate the potential applications of cobalt-doped HAp (Co-HAp) in the biomedical imaging and therapeutic applications. The co-precipitation approach was used to substitute different molar concentrations of Ca2+ ions with cobalt (Co2+) in HAp structure. The synthesized Co-HAp nanoparticles were studied using various sophisticated techniques to verify the success rate of the doping method. The specific crystal structure, functional groups, size, morphology, photoluminescence property, and thermal stability of the Co-HAp nanoparticles were analyzed based on the characterization results. The computational modelling of doped and undoped HAp reveals the difference in crystal structure parameters. The cytotoxicity study (MTT assay and AO/PI/Hoechst fluorescence staining) reveals the non-toxic characteristics of Co-HAp nanoparticles on MDA-MB-231 breast cancer cell lines. The DOX was loaded onto Co-HAp, showing the maximum drug loading capacity for 2.0 mol% Co-HAp. Drug release was estimated in five different pH environments with various time intervals over 72 h. Furthermore, 2.0 mol% Co-HAp shows excellent fluorescence sensitivity with FITC-conjugated MDA-MB-231 cell lines. These results suggest that cobalt improved the fluorescence intensity of FITC-labeled HAp nanoparticles. This work highlights the promising application of Co-HAp nanoparticles with significant enhanced fluorescence activity for imaging-guided drug delivery system.

Enhanced precision of real-time control photothermal therapy using cost-effective infrared sensor array and artificial neural network.

Photothermal therapy (PTT) requires tight thermal dose control to achieve tumor ablation with minimal thermal injury on surrounding healthy tissues. In this study, we proposed a real-time closed-loop system for monitoring and controlling the temperature of PTT using a non-contact infrared thermal sensor array and an artificial neural network (ANN) to induce a predetermined area of thermal damage on the tissue. A cost-effective infrared thermal sensor array was used to monitor the temperature development for feedback control during the treatment. The measured and predicted temperatures were used as inputs of fuzzy control logic controllers that were implemented on an embedded platform (Jetson Nano) for real-time thermal control. Three treatment groups (continuous wave = CW, conventional fuzzy logic = C-Fuzzy, and ANN-based predictive fuzzy logic = P-Fuzzy) were examined and compared to investigate the laser heating performance and collect temperature data for ANN model training. The ex vivo experiments validated the efficiency of fuzzy control with temperature method on maintaining the constant interstitial tissue temperature (80 ± 1.4 °C) at a targeted surface of the tissue. The linear relationship between coagulation areas and the treatment time was indicated in this study, with the averaged coagulation rate of 0.0196 cm2/s. A thermal damage area of 1.32 cm2 (diameter ∼1.3 cm) was observed under P-Fuzzy condition for 200 s, which covered the predetermined thermal damage area (diameter ∼1 cm). The integration of real-time feedback temperature control with predictive ANN could be a feasible approach to precisely induce the preset extent of thermal coagulation for treating papillary thyroid microcarcinoma.

Fluorescence/photoacoustic imaging-guided nanomaterials for highly efficient cancer theragnostic agent.

Imaging modalities combined with a multimodal nanocomposite contrast agent hold great potential for significant contributions in the biomedical field. Among modern imaging techniques, photoacoustic (PA) and fluorescence (FL) imaging gained much attention due to their non-invasive feature and the mutually supportive characteristic in terms of spatial resolution, penetration depth, imaging sensitivity, and speed. In this present study, we synthesized IR783 conjugated chitosan-polypyrrole nanocomposites (IR-CS-PPy NCs) as a theragnostic agent used for FL/PA dual-modal imaging. A customized FL and photoacoustic imaging system was constructed to perform required imaging experiments and create high-contrast images. The proposed nanocomposites were confirmed to have great biosafety, essentially a near-infrared (NIR) absorbance property with enhanced photostability. The in vitro photothermal results indicate the high-efficiency MDA-MB-231 breast cancer cell ablation ability of IR-CS-PPy NCs under 808 nm NIR laser irradiation. The in vivo PTT study revealed the complete destruction of the tumor tissues with IR-CS-PPy NCs without further recurrence. The in vitro and in vivo results suggest that the demonstrated nanocomposites, together with the proposed imaging systems could be an effective theragnostic agent for imaging-guided cancer treatment.

Ultra-widefield photoacoustic microscopy with a dual-channel slider-crank laser-scanning apparatus for in vivo biomedical study.

Photoacoustic microscopy (PAM) is an important imaging tool that can noninvasively visualize the anatomical structure of living animals. However, the limited scanning area restricts traditional PAM systems for scanning a large animal. Here, we firstly report a dual-channel PAM system based on a custom-made slider-crank scanner. This novel scanner allows us to stably capture an ultra-widefield scanning area of 24 mm at a high B-scan speed of 32 Hz while maintaining a high signal-to-noise ratio. Our system's spatial resolution is measured at ∼3.4 µm and ∼37 µm for lateral and axial resolution, respectively. Without any contrast agent, a dragonfly wing, a nude mouse ear, an entire rat ear, and a portion of mouse sagittal are successfully imaged. Furthermore, for hemodynamic monitoring, the mimicking circulating tumor cells using magnetic contrast agent is rapidly captured in vitro. The experimental results demonstrated that our device is a promising tool for biological applications.

Rice starch coated iron oxide nanoparticles: A theranostic probe for photoacoustic imaging-guided photothermal cancer therapy.

In recent years, suitable bioactive materials coated nanoparticles have attracted substantial attention in the field of biomedical applications. The present study emphasizes experimental details for the synthesis of boiling rice starch extract (BRE) coated iron oxide nanoparticles (IONPs) to treat cancer by photoacoustic imaging (PAI)-guided chemo-photothermal therapy. The solvothermal method was used to synthesize IONPs. The physical immobilization method helps to coat BRE-loaded doxorubicin (DOX) molecules on the iron oxide surface. In vitro drug release was estimated in basic (pH 9.0), neutral (pH 7.2), and acidic (pH 4.5) media for varying time periods using ultraviolet-visible spectroscopy. The chemical and physical properties of the synthesized spherical BRE-IONPs were characterized using sophisticated analytical instrumentation. A magnetic saturation experiment was performed with BRE-IONPs for evaluating possible hyperthermia in targeted drug delivery. The biological activity of the synthesized BRE-IONPs was investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and acridine orange/propidium iodide fluorescence cell viability study. BRE-IONPs showed excellent photothermal stability, with a high photothermal conversion efficiency (η = 29.73%), biocompatible property, and high near-infrared region absorption for PAI-guided PTT treatment. This study will provide a better understanding of rice starch as a suitable bioactive coating material for possible theranostic applications.

A portable device with low-power consumption for monitoring mouse vital signs during in vivo photoacoustic imaging and photothermal therapy.

OBJECTIVE: The aim of this study was to monitor the physiological changes and cytotoxic effects of exogenous contrast agents during photoacoustic imaging (PAI) and photothermal therapy (PTT). In this paper, a low-power telemetric device for mouse vital signs monitoring was designed and demonstrated. APPROACH: The power consumption was optimized through hardware and software co-design with a 17% increased operating time compared with typical operation. To demonstrate the feasibility of the monitoring device, PAI and PTT experiments with chitosan-polypyrrole nanocomposites (CS-PPy NCs) as exogenous contrast agents were conducted. Herein, the physiological variation in groups of mice with different CS-PPy NC concentrations was observed and analyzed. MAIN RESULTS: The experimental results indicated the influence of CS-PPy NCs and anesthesia on mouse vital signs in PAI and PTT. Additionally, the association between core temperature, heart rate, and saturation of peripheral oxygen (SpO2) during PAI and PTT was shown. The strong near-infrared absorbance of exogenous contrast agents could account for the increase in mouse core temperature and tumor temperature in this study. Furthermore, high cross-correlation values between core temperature, heart rate, and SpO2 were demonstrated to explain the fluctuation of mouse vital signs during PAI and PTT. SIGNIFICANCE: A design of a vital signs monitoring device, with low power consumption, was introduced in this study. A high cross correlation coefficient of mouse vital signs and the effects of CS-PPy NCs were observed, which explained the mouse physiological variation during the PAI and PTT experiments.