Applications of Nano Drug Delivery Systems in The Diagnosis and Treatment of Cerebral Ischemia-reperfusion Injury
- VernacularTitle:纳米药物递送系统在脑缺血再灌注损伤诊疗中的应用
- Author:
Fan ZHANG
1
;
Yin-Long ZHANG
1
Author Information
- Publication Type:Journal Article
- Keywords: cerebral ischemia-reperfusion injury; drug delivery system; targeted delivery; theranostics; neuroprotection
- From: Progress in Biochemistry and Biophysics 2026;53(10):2609-2628
- CountryChina
- Language:Chinese
- Abstract: Acute ischemic stroke is a major cerebrovascular disease with high disability and mortality rates. Although clinical intravenous thrombolysis and mechanical thrombectomy can restore blood perfusion in ischemic brain tissue, they are highly likely to induce secondary cerebral ischemia-reperfusion injury (CI/RI) after blood reperfusion. The pathological process of CI/RI is extremely complex, presenting as a cascading damage network where oxidative stress outbreaks, mitochondrial dysfunction, excessive neuroinflammation, disruption of the blood-brain barrier structure, imbalance of the neurovascular unit homeostasis, and multiple programmed cell death pathways are intertwined. Various pathological links positively feedback on each other, continuously expanding the scope of cerebral infarction, causing irreversible apoptosis of neurons, and ultimately leading to long-term neurological deficits. At present, commonly used neuroprotective small-molecule drugs in clinical practice, such as edaravone and butylphthalide, have several drawbacks. These include poor blood-brain barrier penetration and low drug enrichment concentration at the lesion site; insufficient lesion targeting and obvious off-target toxic side effects of systemic administration; a narrow treatment time window and the inability of single-target drugs to block multi-pathway cross-linked damage. These limitations have made it difficult to translate a large number of basic research findings into clinical applications. The nanodelivery system, with its four core advantages of tunable physicochemical properties, flexible surface functionalization, integration of multifunctional modules, and response to the pathological microenvironment, can efficiently cross the damaged blood-brain barrier through endocytosis, accumulate directionally in the ischemic penumbra, and release drugs in a targeted manner in response to characteristic signals such as low pH, high reactive oxygen species, and high matrix metalloproteinases at the lesion site. This provides a new technical approach for achieving both precise treatment and early molecular diagnosis of CI/RI. This paper systematically reviews the core pathological mechanisms of CI/RI and outlines six major mainstream nanodrug delivery systems, namely polymer-based (synthetic polymers, natural biopolymers), lipid-based (traditional lipid carriers, intelligent lipid nanoparticles), inorganic nanozyme materials, cell membrane biomimetic nanocarriers, natural extracellular vesicles, and carrier-free self-assembled nanoformulations. It compares the material construction characteristics, brain-targeting mechanisms, neuroprotective advantages, and inherent limitations of each type of carrier. It also elaborates on the recent cutting-edge research progress of nanodrug delivery systems in three directions: targeted single-pathway intervention, multi-pathological pathway collaborative blockade, and multimodal visual imaging diagnosis of CI/RI. Moreover, it analyzes the current core practical bottlenecks restricting the translation of nanodrugs from the laboratory to clinical applications, including long-term in vivo biosafety risks, insufficient lesion targeting accuracy, great difficulty in large-scale and standardized preparation, and the lack of a unified evaluation system for drug efficacy and safety. By integrating frontier research cases of co-delivery of multimodal imaging probes and neuroprotective drugs, this paper distinguishes the functional differences between single-therapeutic nanocarriers and integrated diagnosis and treatment platforms, and clarifies how imaging modules achieve precise lesion localization and dynamic disease course monitoring, providing a clear development context for the research on visual and precise intervention of stroke. From the cross-disciplinary perspectives of biochemistry, materials science, and pharmacy, this paper prospects the development ideas of the next-generation intelligent, highly biocompatible, and integrated diagnosis and treatment nanoplatforms, as well as the promotion of the combined application of nanodelivery technology with clinical thrombolysis and thrombectomy protocols. It is expected to provide systematic and comprehensive theoretical support for the structural optimization, basic research and development, and clinical translation of novel nanodrugs for cerebral ischemia-reperfusion injury.
