Gadolinium‐Encapsulated Graphene Carbon Nanotheranostics for Imaging‐Guided Photodynamic Therapy

Abstract

Photosensitizers (PS) are an essential component of photodynamic therapy (PDT). Conventional PSs are often porphyrin derivatives, which are associated with high hydrophobicity, low quantum yield in aqueous solutions, and suboptimal tumor-to-normal-tissue (T/N) selectivity. There have been extensive efforts to load PSs into nanoparticle carriers to improve pharmacokinetics. The approach, however, is often limited by PS self-quenching, pre-mature release, and nanoparticle accumulation in the reticuloendothelial system organs. Herein, a novel, nanoparticle-based PS made of gadolinium-encapsulated graphene carbon nanoparticles (Gd@GCNs), which feature a high O quantum yield, is reported. Meanwhile, Gd@GCNs afford strong fluorescence and high T relaxivity (16.0 × 10 m s , 7 T), making them an intrinsically dual-modal imaging probe. Having a size of approximately 5 nm, Gd@GCNs can accumulate in tumors through the enhanced permeability and retention effect. The unbound Gd@GCNs cause little toxicity because Gd is safely encapsulated within an inert carbon shell and because the particles are efficiently excreted from the host through renal clearance. Studies with rodent tumor models demonstrate the potential of the Gd@GCNs to mediate image-guided PDT for cancer treatment. Overall, the present study shows that Gd@GCNs possess unique physical, pharmaceutical, and toxicological properties and are an all-in-one nanotheranostic tool with substantial clinical translation potential.

Synthesis and Relaxometric Characterization of New Poly[N,N‐bis(3‐aminopropyl)glycine] (PAPGly) Dendrons Gd‐Based Contrast Agents and Their in Vivo Study by Using the Dynamic Contrast‐Enhanced MRI Technique at Low Field (1 T)

“…1 H-NMR (300 MHz, CDCl 3 , 25°C): 1.69 (4H, q, J = 8, 2 × CH 2 CH 2 CH 2 ), 2.56 (4H, t, J = 8, 2 × NCH 2 CH 2 ), 2.71 (4H, t, J = 8, 2 × CH 2 CH 2 NH 2 ), 3.86 (2H, s, COCH 2 N). 13…”

“…Consequently, the relatively low signal enhancing effect (or longitudinal relaxivity r 1 , s −1 m m −1 ) requires that high concentrations ( i. e ., high doses) of MRI contrast agent have to be administered to eventually obtain sufficient contrast between the blood vessels and its surrounding tissues. A straightforward approach to increase the loading of Gd 3+ per molecule is to attach several Gd(III) chelates to a macromolecular scaffold . An additional advantage of (covalently) attaching multiple Gd(III)‐based complexes to high MW structures is the strong increase in r 1 per Gd 3+ as a result of the strong reduction in the molecular tumbling rate of the Gd(III) complex …”

“…A straightforward approach to increase the loading of Gd 3 + per molecule is to attach several Gd(III) chelates to a macromolecular scaffold. [13,14] An additional advantage of (covalently) attaching multiple Gd(III)-based complexes to high MW structures is the strong increase in r 1 per Gd 3 + as a result of the strong reduction in the molecular tumbling rate of the Gd(III) complex. [8,15] Inulin-Gd-DO3A complexes, [16] several natural and synthetic polymers, such as starch polysaccharide, [17,18] dextran, [19] or polylysine, [20] have been modified and conjugated to contrast agents, and showed good efficiency in imaging.…”

“…t, J = 6, 2 × CH 2 CH 2 NH), 3.69 (2H, br. s, COCH 2 N) 13. C-NMR (300 MHz, CD 3 OD, 25°C): 26.04, 28.84, 38.23, 54.54, 56.78, 80.33, 158.74, 170.07.…”

Magnetic resonance imaging and photothermal conversion properties of Gd‐C nanocomposites for interstitial lymphography

“…Therefore, the combination of carbon materials and Gd based compounds may result in dual‐functional agents for MRI guided PTT of cancer (Huang et al, ). For example, Gd(III)‐doped carbon dots have been proved to be promising as dual fluorescence‐MRI probes (Bourlinos et al, ; Pan et al, ; Yu et al, ), as well as imaging‐guided photodynamic therapy agent (Chen et al, ). For the MRI of lymph cancer particularly; however, there is special limitation in particle size of the contrast agents.…”