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.

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.

In vivo mimicking injectable self-setting composite bio-cement: Scanning acoustic diagnosis and biological property evaluation for tissue engineering applications.

Injectability and self-setting properties are important factors to increase the efficiency of bone regeneration and reconstruction, thereby reducing the invasiveness of hard tissue engineering procedures. In this study, 63S bioactive glass (BG), nano-hydroxyapatite (n-HAp), alumina, titanium dioxide, and methylene bis-acrylamide (MBAM)-mediated polymeric crosslinking composites were prepared for the formulation of an efficient self-setting bone cement. According to the cytocompatibility and physicochemical analyses, all the samples qualified the standard of the bio-composite materials. They revealed high thermal stability, injectability, and self-setting ability supported by ~ 10.73% (maximum) mass loss, ~ 92-93% injectability and 24 ± 5 min of initial setting time. Moreover, a cellular adhesion and proliferation study was additionally performed with osteoblasts like MG-63 cells, which facilitate pseudopod-like cellular extensions on the BG/n-HAp composite scaffold surface. The SAM study was employed to non-invasively assess the self-setting properties of the composite bio-cement using the post injected distribution and physical properties of the phantom. These results validate the significant potential characteristics of the BG/n-HAp self-setting bio-cement (16:4:2:1) for promising minimal-invasive bone tissue engineering 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.

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.

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.