Hydrophilic Quantum Dots Functionalized with Gd(III)-DO3A Monoamide Chelates as Bright and Effective T1-weighted Bimodal Nanoprobes

Abstract

Magnetic resonance imaging (MRI) is a powerful non-invasive diagnostic tool that enables distinguishing healthy from pathological tissues, with high anatomical detail. Nevertheless, MRI is quite limited in the investigation of molecular/cellular biochemical events, which can be reached by fluorescence-based techniques. Thus, we developed bimodal nanosystems consisting in hydrophilic quantum dots (QDs) directly conjugated to Gd(III)-DO3A monoamide chelates, a Gd(III)-DOTA derivative, allowing for the combination of the advantages of both MRI and fluorescence-based tools. These nanoparticulate systems can also improve MRI contrast, by increasing the local concentration of paramagnetic chelates. Transmetallation assays, optical characterization, and relaxometric analyses, showed that the developed bimodal nanoprobes have great chemical stability, bright fluorescence, and high relaxivities. Moreover, fluorescence correlation spectroscopy (FCS) analysis allowed us to distinguish nanosystems containing different amounts of chelates/QD. Also, inductively coupled plasma optical emission spectrometry (ICP – OES) indicated a conjugation yield higher than 75%. Our nanosystems showed effective longitudinal relaxivities per QD and per paramagnetic ion, at least 5 times [per Gd(III)] and 100 times (per QD) higher than the r1 for Gd(III)-DOTA chelates, suitable for T1-weighted imaging. Additionally, the bimodal nanoparticles presented negligible cytotoxicity, and efficiently labeled HeLa cells as shown by fluorescence. Thus, the developed nanosystems show potential as strategic probes for fluorescence analyses and MRI, being useful for investigating a variety of biological processes.

Toward Waveguide-Based Optical Chromatography

“…The wavelength of the laser can then be swept, from the long to short, to perform an absorption-selective size separation. QDs usually have cap layers that change their hydrodynamic radii and their diffusion times in a liquid medium [39]. It would therefore also be possible to QDs of equal semiconductor core radius, through their cap layer thickness.…”

Investigating plasma volume expanders as novel macromolecular MRI‐CEST contrast agents for tumor contrast‐enhanced imaging

“…[16][17][18][19][20][21][22][23][24][25] Recent developments have exploited nanosized systems based on different platforms to increase both contrast efficiency and vascular retention. [26][27][28][29][30][31][32][33][34] However, the selective advantage of Gd-based macromolecular contrast agents is counterbalanced by their longer elimination time from plasma circulation and by safety issues related to the suspected Gd accumulation in normal tissue with consequent implications for clinical approval. 35,36 In the last two decades, a new MRI approach that is able to detect molecules possessing exchangeable protons has been proposed based on the chemical-exchange saturation-transfer (CEST) technique.…”

“…An important class of perfusion gadolinium (Gd)‐based molecules are indeed the blood‐pool agents that noncovalently bind to the serum albumin and are able to report antiangiogenic therapies responses, mainly in association with the dynamic contrast‐enhanced (DCE)‐MRI 16‐25 . Recent developments have exploited nanosized systems based on different platforms to increase both contrast efficiency and vascular retention 26‐34 . However, the selective advantage of Gd‐based macromolecular contrast agents is counterbalanced by their longer elimination time from plasma circulation and by safety issues related to the suspected Gd accumulation in normal tissue with consequent implications for clinical approval 35,36 …”

Mn-Doped Quinary Ag–In–Ga–Zn–S Quantum Dots for Dual-Modal Imaging

“…In recent years, the development of nanoparticles with both PL and MR functionalities has been the object of tremendous efforts. − For more than 20 years, semiconductor quantum dots (QDs) have received high attention as optical contrast agents. Compared to conventional organic fluorophores, QDs exhibit unique optical properties including broad absorption bands, size- and composition-tunable PL emission, and high brightness and photostability. − Numerous strategies like the assembly of QDs with paramagnetic Fe 3 O 4 nanoparticles, − the deposition of a paramagnetic coating at the surface of QDs, or the reverse option consisting in the deposition of QDs at the surface of Fe 3 O 4 nanoparticles, − or finally, the conjugation of QDs with Gd 3+ chelates − have been developed to prepare probes for bimodal imaging. However, some of these nanoparticles have shortcomings such as the decrease of the PL intensity after association with the magnetic center, a high hydrodynamic diameter, or tedious synthesis methods.…”