HMN 2025: How Ultrasmall theranostic nanozyme offers new hope for abdominal aortic aneurysm management

A team led by Professor Hui Wei, a pioneer in nanozyme research at Nanjing University, has unveiled an ultrasmall theranostic nanozyme with the potential to transform the diagnosis and treatment of abdominal aortic aneurysm (AAA)—a highly lethal vascular disease with limited therapeutic options.

The study, published in Science Advances, demonstrates how a precision-engineered nanozyme can provide targeted intervention while simultaneously enabling noninvasive monitoring, opening a path toward a more responsive and patient-friendly clinical approach.

Understanding AAA and oxidative stress

AAA is notorious for its silent progression and devastating outcomes. Although surgical repair remains the mainstream treatment, it is invasive and unsuitable for many patients, especially those with small but unstable aneurysms.

The progression of AAA is closely tied to oxidative stress, where excessive reactive oxygen species drive inflammation, smooth muscle cell loss, matrix degradation, and ultimately vessel rupture. The absence of effective antioxidant therapies has long hindered clinical management.

How the nanozyme targets and treats AAA

To overcome this barrier, the researchers developed OZn, a ROS-responsive nanozyme that encapsulates ultrasmall Prussian blue analog nanoparticles (SPBZn) within an oxidation-sensitive polymer shell. Once administered intravenously, OZn naturally accumulates at aneurysmal lesions due to local inflammation.

The elevated ROS environment triggers rapid shell degradation, releasing SPBZn directly into diseased tissues. The released nanozyme displays potent superoxide dismutase– and catalase–like activities, efficiently suppressing oxidative stress, protecting vascular smooth muscle cells, and reducing pathological calcification—key factors that contribute to aneurysm expansion.

Beyond its therapeutic function, this nanozyme introduces a notable diagnostic advantage. Thanks to the ultrasmall size of SPBZn, the released particles are cleared by the kidneys and appear in urine, where their catalytic activity can be easily detected. This creates an opportunity for simple, noninvasive urinalysis to identify AAA and evaluate treatment response, addressing a major unmet need in a field that currently relies on costly and radiation-based imaging.

Results from animal studies and clinical potential

In animal models, OZn demonstrated clear targeting of aneurysmal sites, with fluorescence and catalytic signals detected only in AAA-bearing subjects. Therapeutically, the nanozyme substantially inhibited aneurysm enlargement, reduced vascular smooth muscle apoptosis, preserved elastin fibers, and dampened macrophage-driven inflammation.

In long-term models, its efficacy outperformed clopidogrel, a standard cardiovascular drug, underscoring the advantage of ROS-responsive release. Histological assessments further confirmed reduced oxidative damage and diminished calcium deposition in treated tissues.

Integrating therapy and real-time monitoring

A distinguishing feature of this system is its ability to provide real-time feedback during therapy. As treatment progressed, the urinary catalytic signal gradually declined, aligning closely with pathological improvements. Once the signal returned to baseline, aneurysm progression was effectively controlled, indicating that treatment could safely conclude. This feedback loop integrates treatment and monitoring into a single streamlined strategy that could greatly enhance patient compliance and reduce reliance on repeated imaging.

The development of this ultrasmall theranostic nanozyme represents an important advance in nanozyme-enabled medicine. By uniting targeted therapy, ROS-responsive activation, and renal-clearable diagnostic output, the platform introduces a versatile and clinically relevant method for managing AAA. As the field moves closer to translation, this work offers a compelling blueprint for how nanozymes can address complex diseases by merging therapeutic and diagnostic capabilities within one intelligent system.

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