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Emerging nanoparticle-based strategies to provide
therapeutic benefits for stroke
Javaria Sundus, Nashwa Amin, Irum Naz Abbasi, Fei Wu, Azhar B. Hussien, Benson OA Botchway, Suhong Ye, Qining Yang, Marong Fang
2026, 21 (5):
1764-1782.
doi: 10.4103/NRR.NRR-D-24-01492
Functional neurological recovery remains the primary objective when treating ischemic stroke.
However, current therapeutic approaches often fall short of achieving optimal outcomes. One
of the most significant challenges in stroke treatment is the effective delivery of neuroprotective
agents across the blood–brain barrier to ischemic regions within the brain. The blood–brain barrier,
while essential for protecting the brain from harmful substances, also restricts the passage of many
therapeutic compounds, thus limiting their efficacy. In this review, we summarizes the emerging
role of nanoparticle-based therapies for the treatment of ischemic stroke and investigate their
potential to revolutionize drug delivery, enhance neuroprotection, and promote functional recovery.
Recent advancements in nanotechnology have led to the development of engineered nanoparticles
specifically designed to overcome the blood–brain barrier, thus enabling the targeted delivery of
therapeutic agents directly to the affected brain areas. Preclinical studies have demonstrated the
remarkable potential of nanoparticle-based therapies to activate key neuroprotective pathways, such
as the phosphoinositide 3-kinase/protein kinase B/cAMP response element-binding protein signaling
cascade, which is crucial for neuronal survival, synaptic plasticity, and post-stroke recovery. By
modulating these pathways, nanoparticles could mitigate neuronal damage, reduce inflammation, and
promote tissue repair. Furthermore, nanoparticles offer a unique advantage by enabling multimodal
therapeutic strategies that simultaneously target multiple pathological mechanisms of ischemic
stroke, including oxidative stress, neuroinflammation, and apoptosis. This multifaceted approach
enhances the overall efficacy of treatment, addressing the complex and interconnected processes that
contribute to stroke-related brain injury. Surface modifications, such as functionalization with specific
ligands or targeting molecules, further improve the precision of drug delivery, enhance targeting
specificity, and prolong systemic circulation, thereby optimizing therapeutic outcomes. Nanoparticlebased
therapeutics represent a paradigm shift for the management of stroke and provide a promising
avenue for reducing post-stroke disability and improving the outcomes of long-term rehabilitation.
By combining targeted drug delivery with the ability to modulate critical neuroprotective pathways,
nanoparticles hold the potential to transform the treatment landscape for ischemic stroke. However,
while preclinical data are highly encouraging, significant challenges remain in translating these
advancements into clinical practice. Further research is needed to refine nanoparticle designs,
optimize their safety profiles, and ensure their scalability for widespread application. Rigorous
clinical trials are essential to validate their efficacy, assess long-term biocompatibility, and address
potential off-target effects. The integration of interdisciplinary approaches, combining insights
from nanotechnology, neuroscience, and pharmacology, will be critical if we are to overcome these
challenges. Ultimately, nanoparticle-based therapies offer a foundation for innovative, precisionbased
treatments that could significantly improve outcomes for stroke patients, thus paving the way
for a new era in stroke care and neurological rehabilitation.
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