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Evaluation of Polymeric Gene Delivery Nanoparticles by Nanoparticle Tracking Analysis and High-throughput Flow Cytometry
Published on: March 1, 2013
Reduction-responsive polymeric micelles for trans-corneal targeted delivery of microRNA-21-5p and glaucoma-specific
Binze Han1, Rong Zhang1, Liping Li1
1Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China. xhsun@shmu.edu.cn.
Abstract:
The therapeutic value of microRNA (miRNA) for the treatment of glaucoma has become a focus of attention. However, naked miRNA cannot cross the corneal barrier and reach the target tissue by itself. Thus, the precise transport of miRNA to the target sites is key to the success of gene therapy. Herein, we selected a miRNA, namely miR-21-5p, based on its unique intraocular pressure (IOP) mechano-sensing property. Moreover, a biocompatible polymeric poly(L-lysine) (PLL) micelle conjugated with collagenase and ABCA1 antibody was judiciously constructed to achieve the trans-corneal and target delivery of miR-21-5p to the trabecular meshwork (TM) and Schlemm's canal (SC) tissues inside the eye. The topically administrated PLL micelles as an eye drop successfully crossed the cornea with the help of collagenase and then preferentially accumulated in the target TM/SC tissues under the guidance of the ABCA1 antibody. When endocytosed by TM/SC cells, the PLL micelles could be decomposed in the reductive lysosomal environment to release miR-21-5p for successfully lowering the IOP by activating the miR-21-5p/eNOS/MMP9 signaling axis, which will open new prospects for glaucoma-specific gene therapy.
Insights
This study developed a novel micelle delivery system for microRNA (miRNA) to treat glaucoma. The system successfully delivered miR-21-5p to target eye tissues, lowering intraocular pressure (IOP) for potential glaucoma gene therapy.
Area of Science:
- Ophthalmology
- Biotechnology
- Gene Therapy
Background:
- Glaucoma treatment faces challenges with microRNA (miRNA) delivery across the corneal barrier.
- Effective transport of miRNA to ocular tissues is crucial for successful gene therapy.
- miR-21-5p demonstrates unique intraocular pressure (IOP) mechano-sensing properties relevant to glaucoma.
Purpose of the Study:
- To develop a novel delivery system for targeted trans-corneal delivery of miR-21-5p for glaucoma treatment.
- To investigate the efficacy of poly(L-lysine) (PLL) micelles conjugated with collagenase and ABCA1 antibody for ocular miRNA delivery.
- To evaluate the potential of this system in lowering intraocular pressure (IOP) via the miR-21-5p/eNOS/MMP9 signaling axis.
Main Methods:
- Construction of biocompatible poly(L-lysine) (PLL) micelles conjugated with collagenase and ABCA1 antibody.
- Topical administration of PLL micelles as eye drops for trans-corneal delivery of miR-21-5p.
- Assessment of micelle accumulation in trabecular meshwork (TM) and Schlemm's canal (SC) tissues and subsequent IOP reduction.
Main Results:
- The developed PLL micelles successfully facilitated trans-corneal delivery of miR-21-5p.
- Collagenase aided corneal penetration, while ABCA1 antibody guided targeted accumulation in TM/SC tissues.
- Released miR-21-5p activated the miR-21-5p/eNOS/MMP9 signaling axis, leading to a significant reduction in IOP.
Conclusions:
- The novel PLL micelle system enables efficient trans-corneal and targeted delivery of miR-21-5p for glaucoma therapy.
- This approach offers a promising strategy for glaucoma-specific gene therapy by lowering IOP.
- The study highlights the potential of engineered nanoparticles for ocular drug and gene delivery.
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