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Lipid Nanocarriers

Gadolinium Nanoparticles

Gadolinium-loaded nanoparticles (GdNPs) are the most promising theranostic agents. GdNPs can be very promising as diagnostics (molecular imaging), therapeutics (molecular therapy), and a combination on a single platform. Clinical MR scans utilize CAs such as gadolinium. In proton MR, gadolinium (Gd3+)-based T1 CAs are applied to reduce the spin-lattice relaxation time ofwater. Moreover, these agents increase the signal from protons, which produce effected voxel to appear “brighter” in ^-weighted image. Higher resolution and signal to noise ratio are provided by T1-weighted sequences. Accelerating the longitudinal molar relaxivity (r1) of T1 CA prolongs rotational correlation time (sr, i.e., the tumbling time of the CA in the bulk water). Higher molecular weight Gd-based agents like Gd functionalized polymer, peptide amphiphiles, or viral capsid, dendrimer, liposomes, nanoparticles, nanomicelles, zeolites, fullerenes, carbon nanotubes, clays, and QDs have been explored [49—53]. Such gadolinium complexes are impeded by cell membrane translocation and are not suitable for targeting. Moreover, Gd-based complexes are associated with difficulty and reproducibility of their fabrications [54]. Till now, only a few gadolinium-based smart MR probes have been developed as responsive to b-galactosidase or myeloperoxidase [55—59]. Kang et al., have developed gadolinium nanoparticles (50—60 nm) conjugated with bifunctional chelates. Two of these have been abbreviated as Gd@SiO2-DO3A and Gd2SiO2-DO2A-BTA. In vivo studies demonstrated that the latter gadolinium nanoparticles exhibited stronger intracellular uptake and cytotoxicity in tumor cells such as SK-HEP1, MDA-MB-231, HeLa, and Hep-3B [60]. In another study, Chun et al. demonstrated intracellular controlled self-assembly of gadolinium nanoparticles [61]. These nanoparticles can act as smart molecular MR CAs. In another study, Li et al. prepared a construct integrating an active gemcitabine metabolite (gemcitabine 5-monophosphate) by coordinating with Gd(III). It self-assembles into nanoparticles and can be applied as theranostics [62]. Such combination demonstrated a stronger T1 contrast signal and simultaneously enhanced retention in mice. Moreover, this combination significantly inhibited tumor growth in mice.

 
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