Exosome-Coated Prussian Blue Nanoparticles for Specific Targeting and Treatment of Glioblastoma.

Glioblastoma is one of the most aggressive and invasive types of brain cancer with a 5-year survival rate of 6.8%. With limited options, patients often have poor quality of life and are moved to palliative care after diagnosis. As a result, there is an extreme need for a novel theranostic method that allows for early diagnosis and noninvasive treatment as current peptide-based delivery standards may have off-target effects. Prussian Blue nanoparticles (PBNPs) have recently been investigated as photoacoustic imaging (PAI) and photothermal ablation agents. However, due to their inability to cross the blood-brain barrier (BBB), their use in glioblastoma treatment is limited. By utilizing a hybrid, biomimetic nanoparticle composed of a PBNP interior and a U-87 cancer cell-derived exosome coating (Exo:PB), we show tumor-specific targeting within the brain and selective thermal therapy potential due to the strong photoconversion abilities. Particle characterization was carried out and showed a complete coating around the PBNPs that contains exosome markers. In vitro cellular uptake patterns are similar to native U-87 exosomes and when exposed to an 808 nm laser, show localized cell death within the specified region. After intravenous injection of Exo:PB into subcutaneously implanted glioblastoma mice, they have shown effective targeting and eradication of tumor volume compared to PEG-coated PBNPs (PEG:PB). Through systemic administration of Exo:PB particles into orthotopic glioblastoma-bearing mice, the PBNP signal was detected in the brain tumor region through PAI. It was seen that Exo:PB had preferential tumor accumulation with less off-targeting compared to the RGD:PB control. Ex vivo analysis validated specific targeting with a direct overlay of Exo:PB with the tumor by both H&E staining and Ki67 labeling. Overall, we have developed a novel biomimetic material that can naturally cross the BBB and act as a theranostic agent for systemic targeting of glioblastoma tissue and photothermal therapeutic effect.

Targeted Biodegradable Near-Infrared Fluorescent Nanoparticles for Colorectal Cancer Imaging.

Colorectal cancer (CRC) is the third leading cause of cancer death in the U.S., and early detection and diagnosis are essential for effective treatment. Current methods are inadequate for rapid detection of early disease, revealing flat lesions, and delineating tumor margins with accuracy and molecular specificity. Fluorescence endoscopy can generate wide field-of-view images enabling detection of CRC lesions and margins; increased signal intensity and improved signal-to-noise ratios can increase both speed and sensitivity of cancer detection. For this purpose, we developed targeted near-infrared (NIR) fluorescent silica nanoparticles (FSNs). We tuned their size to 50-200 nm and conjugated their surface with an antibody to carcinoembryonic antigen (CEA) to prepare CEA-FSNs. The physicochemical properties and biodegradable profiles of CEA-FSN were characterized, and molecular targeting was verified in culture using HT29 (CEA positive) and HCT116 (CEA negative) cells. CEA-FSNs bound to the HT29 cells to a greater extent than to the HCT116 cells, and smaller CEA-FSNs were internalized into HT29 cells more efficiently than larger CEA-FSNs. After intravenous administration of CEA-FSNs, a significantly greater signal was observed from the CEA-positive HT29 than the CEA-negative HCT116 tumors in xenografted mice. In F344-PIRC rats, polyps in the intestine were detected by white-light endoscopy, and NIR fluorescent signals were found in the excised intestinal tissue after topical application of CEA-FSNs. Immunofluorescence imaging of excised tissue sections demonstrated that the particle signals coregistered with signals for both CRC and CEA. These results indicate that CEA-FSNs have potential as a molecular imaging marker for early diagnosis of CRC.

Thermally Induced Morphological and Structural Transformations on Eu2+/Eu3+-Coactivated Calcium Silicate Nanophosphors.

This study presents an approach for synthesizing Eu2+/Eu3+-coactivated Ca2SiO4 nanophosphors, by adjusting the ratio of both activators within a singular host material. Utilizing a hydrothermal method complemented by a postreduction sintering process, we fabricated a series of phosphors characterized by uniform 30-50 nm spherical nanoparticles. These engineered phosphors manifest multichannel luminescence properties and exhibit simultaneous blue and red emission from Eu2+ and Eu3+, respectively. Meticulous control of the 5% H2-95% N2 reduction temperature allowed for precise tuning of the Eu2+ and Eu3+ ions within the host lattice, which enabled the strategic adjustment of their luminescent outputs. Utilizing X-ray photoelectron spectroscopy (XPS), we could discern subtle alterations in the europium oxidation state. By using a transmission electron microscope (TEM) and an X-ray diffractometer (XRD), we found that the subsequent changes by reductive sintering to particle size, morphology, and mixed crystal structures influenced the materials' luminescent characteristics. Our findings herald a significant advancement in solid-state lighting, with the potential for the use of Eu2+/Eu3+-coactivated calcium silicate nanophosphors to develop white light emission technologies endowed with enhanced color rendering and luminous efficacy.

Europium-Doped Calcium Silicate Nanoparticles as High-Quantum-Yield Red-Emitting Phosphors.

Europium ion-activated calcium silicate phosphors (Ca2SiO4:Eu3+) with sharp red-light emission were fabricated via the hydrothermal method. The size of Ca2SiO4:Eu3+ phosphors was controlled between 20 and 200 nm by precursor silicate particle sizes. Systematic studies to determine morphology, crystal phase, and photoluminescence (PL) were carried out for all the phosphors, and their optical efficiencies were compared. We found that the luminescence intensity and emission wavelength of Ca2SiO4:Eu3+ phosphors depend on their particle sizes. Particularly, the Ca2SiO4:Eu3+ synthesized with 20 nm silica seed contains the most intense red emission, high color purity, and high PL quantum yield. For the 20 nm-sized Ca2SiO4:Eu3+ phosphor, PL quantum yields are measured to be above 87.95% and high color purity of 99.8%. The unusually high intensity of 5D0 → 7F4 emission (712 nm) is explained by structural distortion arising from silicate particle size reductions. We show that the obtained phosphor is a suitable candidate for solid-state lighting as a red component through CIE chromaticity coordinate and color purity measurements. Furthermore, the Ca2SiO4:Eu3+ particles are examined for their validity as promising bio-imaging probes through cell labeling and imaging experiments and biodegradability studies.

A Mouse Model of Endometriosis with Nanoparticle Labeling for In Vivo Photoacoustic Imaging.

Endometriosis is a condition of the female reproductive tract characterized by endometrium-like tissue growing outside the uterus. Though it is a common cause of pelvic pain and infertility, there is currently no reliable noninvasive method to diagnose the presence of endometriosis without surgery, and the pathophysiological mechanisms that lead to the occurrence of symptoms require further inquiry. Due to patient heterogeneity and delayed diagnosis, animal models are commonly used to study the development of endometriosis, but these are costly due to the large number of animals needed to test various treatments and experimental conditions at multiple endpoints. Here, we describe a method for synthesis of multimodal imaging gold-fluorescein isothiocyanate (FITC) nanoparticles with preclinical application via induction of nanoparticle-labeled endometriosis-like lesions in mice. Labeling donor endometrial tissue fragments with gold-FITC nanoparticles prior to induction of endometriosis in recipients enables in vivo detection of the gold-labeled lesions with photoacoustic imaging. The same imaging method can be used to visualize embryos noninvasively in pregnant mice. Furthermore, the conjugated FITC dye on the gold nanoparticles allows easy isolation of labeled lesion tissue under a fluorescence dissection microscope. After dissection, the presence of gold-FITC nanoparticles and endometrium-like histology of lesions can be verified through fluorescence imaging, gold enhancement, and immunostaining. This method for in vivo imaging of endometriosis-like lesions and fluorescence-guided dissection will permit new experimental possibilities for the longitudinal study of endometriosis development and progression as well as endometriosis-related infertility.