Gadolinium (III)‐Chelated Deformable Mesoporous Organosilica Nanoparticles as Magnetic Resonance Imaging Contrast Agent

Abstract

limited contribution of standard MRI to the differentiation of benign and malignant tumors and to the characterization of tumor tissues. [2] Therefore, contrast agents are often required for clinical diagnosis in order to enhance signal differences. Approximately 40% of clinical MRI scans are performed with the assistance of contrast agents. [3] Gadolinium (Gd 3+ ) complexes such as Magnevist (Gd-DTPA) are one of the most commonly used T 1 contrast agents in clinics because of their thermodynamic stable and high paramagnetic. However, the lack of tissue specificity, rapid renal clearance, and limited relaxivity of Gd-DTPA mean higher doses during tumor imaging are required, [1b,4] which may cause potential harm to patients. [5] Loading small molecular contrast agent into nanocarriers can overcome their poor neoplastic targetability and modest signal-to-noise ratio, [6] but the short blood circulation of conventional nanocarriers limits further improvement in performance.The constant deformation of red blood cells (RBCs), one of the most common cells in blood, allows them to circulate for ≈120 days. [7] Healthy RBCs can deform and squeeze through Magnetic resonance imaging (MRI) contrast agents, such asMagnevist (Gd-DTPA), are routinely used for detecting tumors at an early stage. However, the rapid clearance by the kidney of Gd-DTPA leads to short blood circulation time, which limits further improvement of the contrast between tumorous and normal tissue. Inspired by the deformability of red blood cells, which improves their blood circulation, this work fabricates a novel MRI contrast agent by incorporating Gd-DTPA into deformable mesoporous organosilica nanoparticles (D-MON). In vivo distribution shows that the novel contrast agent is able to depress rapid clearance by the liver and spleen, and the mean residence time is 20 h longer than Gd-DTPA. Tumor MRI studies demonstrated that the D-MON-based contrast agent is highly enriched in the tumor tissue and achieves prolonged high-contrast imaging. D-MON significantly improves the performance of clinical contrast agent Gd-DTPA, exhibiting good potential in clinical applications.

pH-Responsive Upconversion Mesoporous Silica Nanospheres for Combined Multimodal Diagnostic Imaging and Targeted Photodynamic and Photothermal Cancer Therapy

“…34,35 Finally, by doping the core with Gd, UMSNs can also serve as MRI contrast agents. 36,37 T 1 maps and relaxation rate (1/T 1 ) plots 38,39 demonstrate that UMSNs consistently yielded greater contrast enhancement compared to the clinically used contrast agent Gd-DTPA (at the same concentrations of the lanthanide; Figure 2j).…”

“…Therefore, under NIR irradiation, the fluorescence emission from the upconversion core will excite the Ce6 encapsulated within the pores of the UMSNs to generate cytotoxic reactive oxygen species (ROS) (Supporting Figure 3). The photothermal agent (PTA) Bi 2 Se 3 was additionally incorporated in the core to simultaneously convert absorbed NIR light to heat for thermal imaging and PDT. , Finally, by doping the core with Gd, UMSNs can also serve as MRI contrast agents. , T 1 maps and relaxation rate (1/ T 1 ) plots , demonstrate that UMSNs consistently yielded greater contrast enhancement compared to the clinically used contrast agent Gd-DTPA (at the same concentrations of the lanthanide; Figure j).…”

Advances and applications of nanoparticles in cancer therapy

“…Besides surface alteration, modification of NPs in terms of morphology or particle size will also prolong their circulation time 267 . Inspired by the deformability of red blood cells (to improve their blood circulation), Chen et al's 268 group has constructed novel deformable mesoporous organosilicon NPs (MON). The flexible deformable silica carriers can be deformed in the blood like red blood cells, and thus having a long circulatory half‐life compared to conventional rigid carriers.…”

Hydrogen-Bonded Organic Frameworks Chelated Manganese for Precise Magnetic Resonance Imaging Diagnosis of Cancers

“…9−11 However, Gd-based CAs have drawbacks such as high dosage-related potential risks of brain deposition and nephrogenic systemic fibrosis (NSF) and poor biocompatibility leading to their fast clearance from blood. 12,13 The ability to target lesions and the biocompatibility may be directions for the future development of MRI contrast agent. Manganese (Mn) is a safe and essential trace element in the human body that possesses magnetic properties.…”

“…Magnetic resonance imaging (MRI) is a non-invasive and nonradioactive modality for obtaining tumor tissue information. − To detect early and small lesions in MRI, contrast agents (CAs) are often utilized. , These agents are capable of accelerating the relaxation of protons in water molecules and allowing for greater contrast in the resulting images. , Currently, the most commonly used MRI CAs are made of gadolinium (Gd) chelates. These CAs work by decreasing the longitudinal relaxation time ( T 1 ) of protons. − However, Gd-based CAs have drawbacks such as high dosage-related potential risks of brain deposition and nephrogenic systemic fibrosis (NSF) and poor biocompatibility leading to their fast clearance from blood. , The ability to target lesions and the biocompatibility may be directions for the future development of MRI contrast agent. Manganese (Mn) is a safe and essential trace element in the human body that possesses magnetic properties. , As a result, Mn chelates have emerged as a promising alternative to MRI CAs. − …”