Activatable Nanoparticles: Recent Advances in Redox-Sensitive Magnetic Resonance Contrast Agent Candidates Capable of Detecting Inflammation

Nwasike, Chukwuazam; Purr, Erin; Yoo, Eunsoo; Nagi, Jaspreet Singh; Doiron, Amber L.

doi:10.3390/ph14010069

Cited by 2 publications

(2 citation statements)

References 59 publications

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“…In recent decades, several kinds of MRI contrast agents that were responsive to reductive GSH or ROS have been developed. − However, most of them employed irreversible reaction with the specific ROS or GSH, thus giving irreversible interaction between the probes and analytes. Meanwhile, most of them failed to detect oxidant and antioxidant levels simultaneously.…”

Section: Discussionmentioning

confidence: 99%

Dynamic–Reversible MRI Nanoprobe for Continuous Imaging Redox Homeostasis in Hepatic Ischemia–Reperfusion Injury

Zhang

Nan

et al. 2023

ACS Nano

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Hepatic ischemia–reperfusion (I/R) injury accompanied by oxidative stress is responsible for postoperative liver dysfunction and failure of liver surgery. However, the dynamic non-invasive mapping of redox homeostasis in deep-seated liver during hepatic I/R injury remains a great challenge. Herein, inspired by the intrinsic reversibility of disulfide bond in proteins, a kind of reversible redox-responsive magnetic nanoparticles (RRMNs) is designed for reversible imaging of both oxidant and antioxidant levels (ONOO–/GSH), based on sulfhydryl coupling/cleaving reaction. We develop a facile strategy to prepare such reversible MRI nanoprobe via one-step surface modification. Owing to the significant change in size during the reversible response, the imaging sensitivity of RRMNs is greatly improved, which enables RRMNs to monitor the tiny change of oxidative stress in liver injury. Notably, such reversible MRI nanoprobe can non-invasively visualize the deep-seated liver tissue slice by slice in living mice. Moreover, this MRI nanoprobe can not only report molecular information about the degree of liver injury but also provide anatomical information about where the pathology occurred. The reversible MRI probe is promising for accurately and facilely monitoring I/R process, accessing injury degree and developing powerful strategy for precise treatment.

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Section: Discussionmentioning

confidence: 99%

Dynamic–Reversible MRI Nanoprobe for Continuous Imaging Redox Homeostasis in Hepatic Ischemia–Reperfusion Injury

Zhang

Nan

et al. 2023

ACS Nano

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“…IPC-SPIOs are comprised of superparamagnetic iron oxide nanoparticles (SPIOs) coated in poly(ethylene glycol) (PEG), which are complexed through hydrogen bonding with poly(gallol). 4–6 One of the main challenges in nanomedicine is selectively and specifically delivering nanoparticles to desired sites, which limits the translation of innovations from laboratory to clinical settings. 7–12 An effective targeted nanoparticle avoids off-target effects while improving specific targeting to the disease location.…”

Section: Introductionmentioning

confidence: 99%

Incorporation of Targeting Biomolecule Improves Interpolymer Complex-Superparamagnetic Iron Oxide Nanoparticles Attachment to and Activation of T2 MR Signals in M2 Macrophages

Nwasike¹,

Purr²,

Nagi³

et al. 2023

IJN

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Introduction Inflammatory diseases are the leading cause of death in the world, accounting for 3 out of 5 deaths. Despite the abundance of diagnostic tools for detection, most screening and diagnostic methods are indirect and insufficient as they are unable to reliably discriminate between high-risk or low-risk stages of inflammatory diseases. Previously, we showed that the selective activation of interpolymer complexed superparamagnetic iron oxide nanoparticles (IPC-SPIOs) under oxidative conditions can be detected by a change in T 2 magnetic resonance (MR) contrast. In this work, IPC-SPIOs were further modified by incorporating mannose as a targeting biomolecule to enhance nanoparticle delivery to M2 macrophages at inflammatory sites. Methods Uncoated SPIOs were synthesized via coprecipitation from a mixture of FeCl 2 and FeCl 3 , PEGylated by adsorbing PEG 300 kDa (40 mg/mL in water) to SPIOs (3 mg/mL in water) over 24 hours, and complexed by mixing 0.25 mg/mL aqueous poly(gallol) with 2 mg/mL PEG-SPIOs and adding 1 M of phosphate buffer in a 9:9:2 ratio. Mannose-PEG attachment was accomplished conducting a second complexation of mannose-PEG to IPC-SPIOs. M2 macrophages were treated with 150, 100, and 75 µg/mL of IPC-SPIOs and mannose-IPC-SPIOs to investigate activation of T 2 MRI signals. Results and Discussion Surface modification resulted in a slight reduction in ROS scavenging capacity; however, nanoparticle uptake by M2 macrophages increased by over 50%. The higher uptake did not cause a reduction in cellular viability. In fact, mannose-IPC-SPIOs induced significant T 2 MR contrast in M2 macrophages compared to IPC-SPIOs and nanoparticles exposed to M1 macrophages. M2 macrophages activated over 30% of mannose-IPC-SPIOs after 6 hours of exposure compared to M1 macrophages and untargeted M2 macrophages. These findings demonstrated that mannose-IPC-SPIOs specifically targeted M2 macrophages and scavenged cellular ROS to activate T 2 MR signal, which can be used to detect inflammation.

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Activatable Nanoparticles: Recent Advances in Redox-Sensitive Magnetic Resonance Contrast Agent Candidates Capable of Detecting Inflammation

Cited by 2 publications

References 59 publications

Dynamic–Reversible MRI Nanoprobe for Continuous Imaging Redox Homeostasis in Hepatic Ischemia–Reperfusion Injury

Dynamic–Reversible MRI Nanoprobe for Continuous Imaging Redox Homeostasis in Hepatic Ischemia–Reperfusion Injury

Incorporation of Targeting Biomolecule Improves Interpolymer Complex-Superparamagnetic Iron Oxide Nanoparticles Attachment to and Activation of T2 MR Signals in M2 Macrophages

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