Magnetic resonance imaging (MRI) contrast agents are broadly employed for better clinical trials in MR imaging. Magnevist solution (Gd-DTPA), a clinical MRI contrast agent, possesses inherent shortcomings like poor r 1 relaxation, short half-time, nephrotoxicity, etc. To overcome these problems, Gd-DTPA-grafted protein assemblies (Gd-P-ABs) loading with anticancer drug cisplatin and photosentizer IR-780 are constructed via chelation of Gd 3+ . Gd-P-ABs exhibit dual MR/fluorescence (FL) imaging–guided chemo/photothermal therapy. Interestingly, Gd-P-ABs behave as aggregation-enhanced magnetic resonance imaging with an extremely high r 1 value of 26.391 s −1 m m −1 , which is about 5.5-fold larger than Gd-DTPA (≈4.8 s −1 m m −1 ). Consequently, better MRI performance is presented with the same concentration of Gd ions. When exposed to acidic tumor microenvironment and light irradiation, Gd-P-ABs show significant drug release capacity. Good cell killing ability in vitro is also determined due to effective folate-targeting ability and high photo–heat conversion. In vivo MR/FL imaging results reveal that Gd-P-ABs possess high-sensitivity tumor-targeting imaging and long tumor retention, which are attributed to the folate-targeting ability and small size effect. Combined chemo/photothermal therapy in vivo demonstrates that the tumor can be eventually ablated. Altogether, the Gd-P-ABs possess great potential for clinical imaging-guided tumor therapy.
Yuping Zhang,Ke Xiang,Jinbin Pan,Ran Cheng,Shao-Kai Sun
Contrast-enhanced magnetic resonance imaging (CE-MRI) is a promising approach for the diagnosis of kidney diseases. However, safety concerns, including nephrogenic systemic fibrosis, limit the administration of gadolinium (Gd)-based contrast agents (GBCAs) in patients who suffer from renal impairment. Meanwhile, nanomaterials meet biosafety concerns because of their long-term retention in the body. Herein, we propose a small-molecule manganese-based imaging probe Mn-PhDTA as an alternative to GBCAs to assess renal insufficiency for the first time. Mn-PhDTA was synthesized via a simple three-step reaction with a total yield of up to 33.6%, and a gram-scale synthesis can be realized. Mn-PhDTA has an r1 relaxivity of 2.72 mM–1 s–1 at 3.0 T and superior kinetic inertness over Gd-DTPA and Mn-EDTA with a dissociation time of 60 min in the presence of excess Zn2+. In vivo and in vitro experiments demonstrate their good stability and biocompatibility. In the unilateral ureteral obstruction rats, Mn-PhDTA provided significant MR signal enhancement, enabled distinguishing structure changes between the normal and damaged kidneys, and evaluated the renal function at different injured stages. Mn-PhDTA could act as a potential MRI contrast agent candidate for the replacement of GBCAs in the early detection of kidney dysfunction and analysis of kidney disease progression.
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