Photouncaging Nanoparticles for MRI and Fluorescence Imagingin Vitroandin Vivo

Abstract

Multimodal and multifunctional nanomaterials are promising candidates for bioimaging and therapeutic applications in the nanomedicine settings. Here we report the preparation of photouncaging nanoparticles with fluorescence and magnetic modalities and evaluation of their potentials for in vitro and in vivo bioimaging. Photoactivation of such bimodal nanoparticles prepared using photouncaging ligands, CdSe/ZnS quantum dots, and super paramagnetic iron oxide nanoparticles results in the systematic uncaging of the particles, which is correlated with continuous changes in the absorption, mass and NMR spectra of the ligands. Fluorescence and magnetic components of the bimodal nanoparticles are characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and elemental analyses using energy dispersive X-ray (EDX) spectroscopy and X-ray photoelectron spectroscopy (XPS). Bioconjugation of the nanoparticles with peptide hormones renders them with biocompatibility and efficient intracellular transport as seen in the fluorescence and MRI images of mouse melanoma cells (B16) or human lung epithelial adenocarcinoma cells (H1650). Biocompatibility of the nanoparticles is evaluated using MTT cytotoxicity assays, which show cell viability over 90%. Further, we combine MRI and NIR fluorescence imaging in C57BL/6 (B6) mice subcutaneously or intravenously injected with the photouncaging nanoparticles and follow the in vivo fate of the nanoparticles. Interestingly, the intravenously injected nanoparticles initially accumulate in the liver within 30 min post injection and subsequently clear by the renal excretion within 48 h as seen in the time-dependent MRI and fluorescence images of the liver, urinary bladder, and urine samples. Photouncaging ligands such as the ones reported in this article are promising candidates for not only the site-specific delivery of nanomaterials-based contrast agents and drugs but also the systematic uncaging and renal clearance of nanomaterials after the desired in vivo application.

Quantum dots: bright and versatile in vitro and in vivo fluorescence imaging biosensors

“…The small contrast agents also facilitated removal after the imaging process. 342 Another approach is layer-by-layer assembly using differently charged materials to form hybrid structures. 343 Because magnetic QDs provide advantages for imaging, sensing, and bioseparation they had a large impact on biomedical research.…”

Facile synthesis of gadolinium (III) chelates functionalized carbon quantum dots for fluorescence and magnetic resonance dual-modal bioimaging

“…Therefore, it is highly desirable to design novel imaging agents which are synergistically combining two or more imaging modalities to address issues such as resolution, sensitivity, and tissue penetration [7][8][9][10][11][12][13][14][15][16]. While, nanoparticles (NPs) provide a robust framework in which two or more components can be integrated to offer multifunctional and synergetic applications [17,18].…”

“…While, nanoparticles (NPs) provide a robust framework in which two or more components can be integrated to offer multifunctional and synergetic applications [17,18]. In this context, nanoscale dual-modal imaging probes combining fluorescence/MR modalities offer possibilities to obtain multiple imaging data for more precise cancer diagnosis and its more efficient management [10][11][12][13][14][15][16]. Fluorescent NPs such as organic dye or metal complex-encapsulated silica NPs (SiNPs) [10,11], semiconductor quantum dots (QDs) [12], lanthanide complexes and upconversion NPs [13][14][15], have been employed as the framework in the construction of dual-modal fluorescence/MR imaging probes, where covalently or non-covalently conjugated iron oxide nanoparticles and/or gadolinium chelates always serve as the magnetic probes.…”

Toward Biocompatible Semiconductor Quantum Dots: From Biosynthesis and Bioconjugation to Biomedical Application

“…314 Recently, Biju and colleagues produced photouncaging QD-Fe 3 O 4 conjugates by reacting biotin-modified Fe 3 O 4 nanoparticles with streptavidinfunctionalized QDs. 315 They adjusted the reaction ratio to make each Fe 3 O 4 nanoparticle be coated by approximately ten QDs. The obtained QD-Fe 3 O 4 conjugates show good biocompatibility and can be applied for in vitro and in vivo dual-modal imaging of mouse melanoma cells and human lung epithelial adenocarcinoma cells.…”