TABLE 3.

Comparative design characteristics of ROS-interacting cardiovascular delivery platforms.

Platform strategy	Primary ROS/redox function	Relative advantage	Principal limitation	Most plausible context	Representative refs
ROS-triggered hydrogels/microgels	ROS-dependent cleavage, degradation, or staged release	High local retention; spatial and temporal control	Often requires direct cardiac administration; responsiveness not always quantified	Post-MI repair, fibrosis, staged remodeling; selected MIRI	(Cao et al., 2026; Hu et al., 2026; Qin et al., 2026; Song L. et al., 2025; Wang et al., 2022; Zhen et al., 2025)
ROS-responsive nanoparticles/liposomes	Triggered release plus systemic or cellular targeting	Potential peri-reperfusion use and multilevel targeting	Biodistribution, clearance, and activation thresholds inconsistently characterized	Acute MIRI and targeted cardiomyocyte delivery	(Li et al., 2020; Wang et al., 2024c; Weng et al., 2022)
Direct antioxidant/scavenging carriers	Direct reduction of oxidative burden	Mechanistically straightforward; compatible with targeting	Does not necessarily provide stimulus-controlled release	Acute cytoprotection and microenvironment conditioning	(Ai et al., 2021; Cheng et al., 2019; Hu et al., 2024; Liao et al., 2022; Tan et al., 2024)
Catalytic nanozymes/enzyme carriers	Repeated catalytic ROS conversion	Potential sustained detoxification and multi-enzyme activity	Persistence, clearance, component attribution, chronic safety	MIRI, mitochondrial injury, persistent oxidative stress	(Altshuler et al., 2021; Chen et al., 2025b; Dai et al., 2026; Fu et al., 2026; Gong et al., 2025; Wang et al., 2025c; Xu et al., 2026; Zhu et al., 2025)
Mitochondria-targeted systems	Delivers scavengers, inhibitors, nanozymes, or gases to mitochondria	Strong alignment with mitochondrial ROS and regulated cell death	Added targeting complexity; no head-to-head architecture comparison	Particularly relevant to acute MIRI	(Cheng et al., 2019; Ikeda et al., 2016; Wang et al., 2025c; Wang et al., 2026; Wang et al., 2025d; Zhang et al., 2022; Zhu et al., 2025)
Oxygen-generating systems	Couples redox regulation with local oxygen production	Addresses hypoxia and oxidative stress together	Oxygen-generation requirements and exposure not standardized	Regenerative MI repair and cell-support strategies	(Ding et al., 2022; Ding et al., 2020; Shiekh et al., 2022; Song Z et al., 2025)
NO/CO/H2S systems	Modulates redox-gas signaling with local or triggered release	Targets signaling pathways beyond ROS scavenging	Dose-release control and systemic exposure require dedicated safety study	MIRI, angiogenesis, inflammation, pyroptosis, remodeling	(Hao et al., 2022; Vong et al., 2018; Wang et al., 2026; Wang et al., 2025e; Wu et al., 2025a)
Biological redox/immunometabolic systems	Modulates endogenous antioxidant, metabolic, or inflammatory circuitry	Targets self-amplifying biological pathways	Causal attribution between ROS and broader biology can be difficult	Inflammation resolution and post-MI repair	(Chen et al., 2025a; Hu et al., 2024; Mesfin et al., 2025; Pan et al., 2025; Wang et al., 2025d; Xue et al., 2026)