AniView Supports Nanotheranostic Platform Research: A closed-loop myocardial infarction theranostic platform activated by macrophage-derived nitric oxide and acidic microenvironment

New progress has been made in precision diagnosis and treatment of myocardial infarction using a macrophage NO/acidic microenvironment dual-responsive closed-loop theranostic nanoplatform.

The team of Tong Jiayi and Yang Fang from Southeast University developed a platelet membrane-biomimetic nanotheranostic system, PM720@NRP. Their findings were published in Bioactive Materials (2026, IF = 23.6, Chinese Academy of Sciences Q1 TOP journal), a leading journal in the field of biomaterials.

This study provides a new paradigm for precision cardiovascular immunotheranostics by developing a platelet membrane-biomimetic nanoplatform, PM720@NRP, designed to exploit the pathological characteristics of myocardial infarction to construct a closed-loop theranostic system. The platform enables NO-activated NIR-II imaging and machine learning-based non-invasive quantification of inflammation, achieves pH-gated on-demand release of FTY720, and promotes angiogenesis synergistically, thereby precisely improving cardiac function after myocardial infarction.

Experiments using Aniview

Inflammatory imbalance in macrophages after myocardial infarction is a key driver of ventricular remodeling and progression to heart failure. Currently, clinical practice lacks diagnostic methods for non-invasive quantification of pro-inflammatory macrophage activity in lesions, as well as targeted immunoreprogramming therapies, while systemic administration of immunomodulators is associated with significant adverse effects. Pro-inflammatory macrophages in myocardial infarction lesions secrete high levels of NO and are accompanied by a local acidic microenvironment, which can serve as endogenous trigger signals for intelligent theranostics. To investigate NO-responsive inflammatory imaging, myocardial infarction-targeted accumulation, and in vivo biodistribution and metabolic characteristics of the biomimetic nanoplatform PM720@NRP, the study employed the AniView Phoenix Full-Spectrum Animal In Vivo Imaging System from Guangzhou Biolight Biotechnology Co., Ltd. to dynamically track the evolution of inflammation and organ distribution.

Validation of NO Responsiveness and Specificity

To verify the sensitivity and molecular specificity of PM720@NRP in response to nitric oxide, in vitro optical performance validation experiments were conducted. In the quantitative responsiveness experiment, the probe was co-incubated with gradient concentrations of the NO donor tert-butyl nitrite for 12 h. The AniView Phoenix imaging system was used to collect fluorescence signals in the NIR-II window under 808 nm excitation and 1064 nm long-pass filtering, establishing the dose-dependent relationship between fluorescence intensity and NO concentration. The results showed that under 808 nm excitation, the NIR-II fluorescence intensity of the system gradually increased with increasing NO donor concentration, reaching a plateau at approximately 30–40 μM (Figure 1I). When the NO donor concentration was fixed, fluorescence intensity decreased linearly as the concentration of the NRP probe decreased (Figure 1J). Specificity validation against various endogenous biological substances showed that the probe exhibited a significant fluorescence turn-on response only in the presence of NO (Figure 1K).

Figure 1. Validation of Macrophage Polarization and In Vitro Immunomodulatory Imaging

Validation of Macrophage Polarization and In Vitro Immunomodulatory Imaging

An in vitro polarization model of bone marrow-derived macrophages (BMDMs) was established. Lipopolysaccharide (LPS) combined with interferon-γ (IFN-γ) was used to induce the pro-inflammatory phenotype, while interleukin-4 (IL-4) was used to induce the anti-inflammatory phenotype, thereby simulating different inflammatory states in myocardial infarction lesions. After the polarized macrophages were co-incubated with PM720@NRP for 6 h, the AniView Phoenix imaging system was used to collect NIR-II fluorescence signals under 808 nm excitation and 1064 nm long-pass filtering, directly validating the probe's ability to specifically respond to and image inflammatory macrophages. The results showed that the NIR-II fluorescence intensity in the PM720@NRP treatment group loaded with the FTY720 drug was significantly lower than that in the unloaded control carrier group, PM@NRP (Figure 2C), indicating that the platform can effectively reduce the pro-inflammatory activity of macrophages and decrease NO production, thereby exerting an immunoreprogramming effect.

Figure 2.

In Vivo NO-Responsive Imaging

To verify the specificity of the imaging signals, PM720@NRP was injected into healthy mice and mice with myocardial infarction, respectively. The results showed that the NIR-II signal in healthy hearts was almost negligible, confirming that non-macrophage-derived NO at physiological baseline levels did not produce interfering fluorescence (Figures 3E and 3F). This demonstrates that the NIR-II emission of the platform can specifically characterize the level of NO derived from pro-inflammatory macrophages within infarcted myocardium. Longitudinal in vivo imaging after administration showed that the unloaded control carrier group, PM@NRP, exhibited the strongest fluorescence signal at 48 h, reflecting the carrier's effective targeting under an unregulated inflammatory state (Figures 3G and 3H). In contrast, the fluorescence signal in the PM720@NRP treatment group declined significantly over the same period, consistent with the therapeutic effects of the platform in regulating macrophage polarization and reducing NO production.

Figure 3.

DOI： 10.1016/j.bioactmat.2026.05.045