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Published on: August 4, 2022
A sequentially targeted and pathology-responsive nanoplatform for synergistic treatment of dry eye disease via
Liandi Huang1,2, Xin Liu3, Ying Yuan1,2
1Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai, 200080, China.
Abstract:
The treatment of complex inflammatory diseases like dry eye disease (DED) is hampered by the intertwined pathologies of inflammation and oxidative stress, which form a self-amplifying vicious cycle. Here, we report an intelligent nanoplatform (CFMPDA) designed to actively navigate and disrupt this cycle through sequential, pathology-responsive targeting. CFMPDA is constructed by encapsulating the anti-inflammatory agent Fuziline within a mesoporous polydopamine (MPDA) nanoscavenger and conjugating CCL2-targeting antibodies on its surface. This design enables a two-stage therapeutic strategy: first, CCL2-mediated anchoring to the inflamed cornea, providing disease severity-dependent retention that overcomes rapid ocular clearance; second, subsequent mitochondrial targeting to deliver combined anti-inflammatory and antioxidant therapy directly to the organelle generating pathogenic ROS. In vivo, CFMPDA demonstrated potent, synergistic efficacy in a DED mouse model, simultaneously suppressing the inflammatory cascade (IL-1β, IL-6, TNF-α, MMP9, T cell infiltration) and quenching oxidative stress, leading to comprehensive tissue repair and functional recovery that surpassed the clinical standard-Fluorometholone. This work establishes a versatile nanotechnology blueprint-responsive bio-interfacing coupled with programmed subcellular delivery-for the synergistic treatment of inflammatory disorders characterized by chemokine upregulation and mitochondrial dysfunction.
Insights
This study introduces an intelligent nanoplatform (CFMPDA) that targets inflammation and oxidative stress in dry eye disease (DED). CFMPDA disrupts the disease cycle by delivering combined therapies sequentially to inflamed eye tissues and mitochondria.
Area of Science:
- Nanotechnology
- Biomedical Engineering
- Ophthalmology
Background:
- Dry eye disease (DED) involves complex inflammation and oxidative stress cycles.
- Current treatments for DED face challenges due to intertwined pathologies and rapid ocular clearance.
Purpose of the Study:
- To develop an intelligent nanoplatform (CFMPDA) for sequential, pathology-responsive targeting to disrupt the inflammation-oxidative stress cycle in DED.
- To investigate the therapeutic efficacy of CFMPDA in a DED mouse model.
Main Methods:
- CFMPDA constructed with Fuziline, mesoporous polydopamine (MPDA), and CCL2-targeting antibodies.
- Two-stage targeting: CCL2-mediated anchoring to inflamed cornea, followed by mitochondrial delivery of anti-inflammatory and antioxidant agents.
- In vivo evaluation in a DED mouse model, assessing inflammatory markers, oxidative stress, and tissue repair.
Main Results:
- CFMPDA demonstrated potent, synergistic efficacy in a DED mouse model.
- Simultaneous suppression of inflammatory cascade (IL-1β, IL-6, TNF-α, MMP9, T cell infiltration) and oxidative stress.
- Comprehensive tissue repair and functional recovery exceeding the clinical standard (Fluorometholone).
Conclusions:
- CFMPDA effectively disrupts the vicious cycle of inflammation and oxidative stress in DED.
- The nanoplatform offers a versatile blueprint for synergistic treatment of inflammatory disorders with chemokine upregulation and mitochondrial dysfunction.
- This approach overcomes rapid ocular clearance and achieves targeted subcellular delivery for enhanced therapeutic outcomes.
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