Cerebral Ischemic Stroke mostly occurs in elderly people, and is a condition caused when there isn’t enough blood flow to the brain to meet metabolic demand. Due to high expenses and the sudden decline of people's quality of life after having a stroke, early diagnosis is considered the most important. However, the research on MRI probes and targeted therapy still remains in the early stages.

To find possible treatments, several studies and the development of drugs are ongoing, as well as the ways to increase the impact of these drugs. Creating new nanocarrier systems using biodegradable polymeric micelles is one of the possible ways to increase drug effectiveness.

This research is about new intelligent nanocarrier systems for magnetic resonance imaging (MRI), based on biodegradable polymeric micelles in order to detect cerebral ischemic areas.

A novel type of pH-responsive biodegradable copolymer was developed based on methyloxy-poly(ethylene glycol)-block-poly[dopamine-2-(dibutylamino) ethylamine-L-glutamate] (mPEG-b-P(DPA-DE)LG), and applied to act as an intelligent nanocarrier system for magnetic resonance imaging (MRI).

The mPEGb-P(DPA-DE)LG copolymer was synthesized by a typical ring opening polymerization of N-carboxyanhydrides (NCAs-ROP) using mPEG-NH2 as a macroinitiator, and two types of amine-terminated dopamine groups and pH-sensitive ligands were grafted onto a side chain by a sequential aminolysis reaction. This design greatly benefits from the addition of the dopamine groups to facilitate self-assembly, as these groups can act as high-affinity anchors for iron oxide nanoparticles, thereby increasing long-term stability at physiological pH.

The mPEG moiety in the copolymers helped the nanoparticles to remain well dispersed in an aqueous solution, and pH-responsive groups could control the release of hydrophobic Fe3O4 nanoparticles in an acidic environment. The particle size of the Fe3O4-loaded mPEG-b-P(DPA-DE) LG micelles was measured by dynamic light scattering (DLS) and cryo-TEM. The superparamagnetic properties of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles were confirmed by a superconducting quantum interference device (SQUID). T2-weighted magnetic resonance imaging (MRI) of Fe3O4-loaded mPEG-b-P(DPA-DE)LG phantoms exhibited enhanced negative contrast with an r2 relaxivity of approximately 106.7 mM−1 s−1.

To assess the ability of the Fe3O4-loaded mPEG-P(DE-DPA)LG micelles to act as MRI probes, we utilized a cerebral ischemia disease rat model with acidic tissue. We found that a gradual change in contrast in the cerebral ischemic area could be visualized by MRI after 1 hour, and maximal signal loss was detected after 24 h post-injection. These results demonstrated that the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles can act as pH-triggered MRI probes for diagnostic imaging of acidic athological tissues.

These results suggest that, due to their unique acid-triggered abilities, the pH-responsive mPEG-b-P(DPA-DE)LG copolymers may have more applications in the biomedical field from MR diagnostic imaging, to therapeutics for other acidic pathologic tissues.

The result of this research was published in the journal nanoscale of Royal Society of Chemistry, UK.