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.

Smart Low Level Laser Therapy System for Automatic Facial Dermatological Disorder Diagnosis.

Computer-aided diagnosis using dermoscopy images is a promising technique for improving the efficiency of facial skin disorder diagnosis and treatment. Hence, in this study, we propose a low-level laser therapy (LLLT) system with a deep neural network and medical internet of things (MIoT) assistance. The main contributions of this study are to (1) provide a comprehensive hardware and software design for an automatic phototherapy system, (2) propose a modified-U2Net deep learning model for facial dermatological disorder segmentation, and (3) develop a synthetic data generation process for the proposed models to address the issue of the limited and imbalanced dataset. Finally, a MIoT-assisted LLLT platform for remote healthcare monitoring and management is proposed. The trained U2-Net model achieved a better performance on untrained dataset than other recent models, with an average Accuracy of 97.5%, Jaccard index of 74.7%, and Dice coefficient of 80.6%. The experimental results demonstrated that our proposed LLLT system can accurately segment facial skin diseases and automatically apply for phototherapy. The integration of artificial intelligence and MIoT-based healthcare platforms is a significant step toward the development of medical assistant tools in the near future.

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.

Full-view in vivo skin and blood vessels profile segmentation in photoacoustic imaging based on deep learning.

Photoacoustic (PA) microscopy allows imaging of the soft biological tissue based on optical absorption contrast and spatial ultrasound resolution. One of the major applications of PA imaging is its characterization of microvasculature. However, the strong PA signal from skin layer overshadowed the subcutaneous blood vessels leading to indirectly reconstruct the PA images in human study. Addressing the present situation, we examined a deep learning (DL) automatic algorithm to achieve high-resolution and high-contrast segmentation for widening PA imaging applications. In this research, we propose a DL model based on modified U-Net for extracting the relationship features between amplitudes of the generated PA signal from skin and underlying vessels. This study illustrates the broader potential of hybrid complex network as an automatic segmentation tool for the in vivo PA imaging. With DL-infused solution, our result outperforms the previous studies with achieved real-time semantic segmentation on large-size high-resolution PA images.

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.

Folic acid-conjugated chitosan-functionalized graphene oxide for highly efficient photoacoustic imaging-guided tumor-targeted photothermal therapy.

Multifunctional theranostic agents have recently attracted a great deal of attention in field of biomedicine. In the present work, folic acid-conjugated chitosan-functionalized graphene oxide (FA-CS-GO) has been developed as a new type of multifunctional nanomaterial for near-infrared fluorescence (FL)/photoacoustic imaging-(PAI) guided photothermal therapy (PTT) of cancer. In vitro results showed that the FA-CS-GO was able to completely destroy cancer cells under laser irradiation. More importantly, in vivo experiments showed that in the presence of targeted FA-CS-GO with laser irradiation, the tumors were completely inhibited, with no recurrence within 20 days. A high photoacoustic signal was detected in the tumor area of mice 24 h after the injection of FA-CS-GO, demonstrating the ability of FA-CS-GO to function as a new PAI contrast agent. Altogether, FA-CS-GO showed a high tumor-targeting efficiency, powerful photothermal effect, and outstanding PAI. This study is considered the first where multifunctional nanomaterials were used for highly efficient FL/PAI-guided tumor-targeted PTT, which is a promising avenue for theranostic nanomedicine.