A neutral polydisulfide containing Gd(III) DOTA monoamide as a redox‐sensitive biodegradable macromolecular MRI contrast agent

Abstract

This work aims to develop safe and effective gadolinium (III)-based biodegradable macromolecular MRI contrast agents for blood pool and cancer imaging. A neutral polydisulfide containing macrocyclic Gd-DOTA monoamide (GOLS) was synthesized and characterized. In addition to studying the in vitro degradation of GOLS, its kinetic stability was also investigated in an in vivo model. The efficacy of GOLS for contrast enhanced MRI was examined with female BALB/c mice bearing 4T1 breast cancer xenografts. The pharmacokinetics, biodistribution and metabolism of GOLS were also determined in mice. GOLS has an apparent molecular weight of 23.0 kDa with T1 relaxivities of 7.20 mM−1s−1 per Gd at 1.5 T, and 6.62 mM−1s−1 at 7.0T. GOLS had high kinetic inertness against transmetallation with Zn2+ ions and its polymer backbone was readily cleaved by L-cysteine. The agent showed improved efficacy for blood pool and tumor MR imaging. The structural effect on biodistribution and in vivo chelation stability was assessed by comparing GOLS with Gd(HP-DO3A), a negatively charged polydisulfide containing Gd-DOTA monoamide GODC, and a polydisulfide containing Gd-DTPA-bisamide (GDCC). GOLS showed high in vivo chelation stability and minimal tissue deposition of gadolinium. The biodegradable macromolecular contrast agent GOLS is a promising polymeric contrast agent for clinical MR cardiovascular imaging and cancer imaging.

Anti-Tumor Metastasis via Platelet Inhibitor Combined with Photothermal Therapy under Activatable Fluorescence/Magnetic Resonance Bimodal Imaging Guidance

“…Xylenol Orange was added as an indicator to monitor the complexation process and purification. Then the final solution was lyophilized to afford a solid . MS­(C 56 H 81 GdN 8 O 7 S 2 + ) calculated: 1199.68, found [M] + : 1199.49.…”

“…PerkinElmer Enspire multifunctional microplate reader was used to measure the fluorescence and UV–vis absorption spectra, and the data was processed by Enspire Workstation (version 4.13.3005.1482), deionized water was used as a baseline calibration and IR780 was served as a control. The Gd content of DPC@ICD-Gd-Tic was evaluated by the inductive coupled plasma-optical emission spectrometry (ICP-OES, Optima 5300DV) by treatment with aqua regia to achieve ionization state and comparison with standard curve …”

“…DPC@ICD-Gd-Tic and DP@ICD-Gd-Tic were intravenously injected at a clinical dose of 0.1 mmol-Gd/kg and then monitored at specified time. 2D spin echo sequence was set with the following parameters: (TR = 500 ms, TE = 8.06 ms, flip angle = 90°, slice thickness = 0.688 mm, slice number = 32, average = 3, matrix = 100 × 512, field of view = 10 cm × 3 cm, resolution = 0.195 mm × 0.3 mm), after scanning, mice were sacrificed and major organs were extracted to acquire MRI biodistribution result. , …”

“…Then the final solution was lyophilized to afford a solid. 37 2.4. Construction of DPC@ICD-Gd and DPC@ICD-Gd-Tic Nanoparticles.…”

Octreotide Functionalized Nano-Contrast Agent for Targeted Magnetic Resonance Imaging

“…Non-site-specific T 1 polymer nanocontrast agents can passively target tumor cells via the enhanced permeation and retention (EPR) effect. To improve the accumulation of contrast agents at precise sites, various targeting moieties such as peptides or antibodies have been conjugated onto polymer nanoparticle contrast agents to improve MRI efficiency through receptor-mediated active targeting. − For example, Peptide T7 (HAIYPRH) has high affinity for Transferrin receptors which are highly expressed on liver cancer cells and brain glioma cells . GRGDS peptides have been conjugated onto polymer-based nanoparticle MRI contrast agents formed by self-assembly of linear comb-like polymers, and in vitro results clearly showed an increased uptake within U87MG glioblastoma cells .…”