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Published on: September 27, 2013
Nanoparticles responsive to the inflammatory microenvironment for targeted treatment of arterial restenosis
Shibin Feng1, Ying Hu2, Song Peng1
1Department of Cardiology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
Insights
Novel nanomedicines targeting inflammation show promise for preventing arterial restenosis after procedures. These responsive nanoparticles deliver drugs effectively to diseased sites, reducing restenosis in a rat model.
Area of Science:
- Biomedical Engineering
- Materials Science
- Pharmacology
Background:
- Coronary arterial disease (CAD) is a leading global cause of death.
- Arterial restenosis following percutaneous coronary interventions is a significant clinical challenge.
- Current treatments lack effective prevention strategies for restenosis.
Purpose of the Study:
- To investigate inflammation-triggerable nanomedicines for targeted therapy of arterial restenosis.
- To develop and evaluate pH- and ROS-responsive nanoparticles for drug delivery.
- To assess the efficacy of these nanotherapies in preclinical models of restenosis.
Main Methods:
- Synthesis of pH-responsive (acetalated β-cyclodextrin) and ROS-responsive (oxidation-labile functionalized β-cyclodextrin) nanoparticles.
- Fabrication of rapamycin-loaded responsive nanotherapies.
- In vitro characterization, hydrolysis, and release studies.
- In vitro cell culture studies with rat vascular smooth muscle cells.
- In vivo evaluation in a rat model of balloon angioplasty-induced arterial restenosis.
Main Results:
- Developed and characterized pH- and ROS-responsive nanoparticles and nanotherapies.
- Demonstrated desirable responsive release profiles and good safety profiles in vitro and in vivo.
- Showed effective cellular uptake and enhanced anti-proliferative/anti-migratory effects of rapamycin.
- Responsive nanotherapies significantly attenuated neointimal hyperplasia in a rat restenosis model compared to non-responsive counterparts.
Conclusions:
- Inflammation-triggerable nanomedicines hold significant potential for managing vascular restenosis.
- Targeted drug delivery via responsive nanoparticles offers a promising therapeutic strategy.
- Selective drug release at inflamed sites can effectively combat arterial restenosis.
Abstract:
Coronary arterial disease (CAD) remains the leading cause of death globally. Percutaneous coronary interventions are frequently used nonsurgical techniques for treating CAD, which may unfortunately lead to arterial restenosis. Currently, there are no effective drugs that can thoroughly prevent restenosis. We hypothesize inflammation-triggerable nanomedicines may function as effective therapeutics for targeted therapy of restenosis, by preferentially releasing their payload at the diseased site. To demonstrate our hypothesis and develop targeted nanotherapies for restenosis, this study was designed to examine effectiveness of nanomedicines responsive to the inflammatory microenvironment with mild acidity and high reactive oxygen species (ROS). To this end, an acetalated β-cyclodextrin (β-CD) material (Ac-bCD) was synthesized as a pH-responsive carrier material, while a ROS-responsive material (Ox-bCD) was produced by hydrophobic functionalization of β-CD with an oxidation-labile group. Based on these two responsive materials, either pH- or ROS-responsive nanoparticles (NPs) were produced by a nanoprecipitation technique and fully characterized. Using rapamycin (RAP) as a candidate drug, responsive nanotherapies were fabricated. In vitro hydrolysis and release studies confirmed these nanovehicles and nanotherapies exhibited desirable responsive behaviors. Both in vitro cell culture and in vivo evaluations revealed their good safety profile. These responsive NPs could be effectively internalized by rat vascular smooth muscle cells, which in turn notably potentiated anti-proliferation and anti-migration activities of RAP. After intravenous (i.v.) injection, NPs may be accumulated at the injured site in the carotid artery of rats subjected to balloon angioplasty injury. Compared with a non-responsive nanotherapy based on poly(lactide-co-glycolide), treatment with either pH- or ROS-responsive nanotherapy by i.v. injection more effectively attenuated neointimal hyperplasia in a rat model of arterial restenosis. Accordingly, nanotherapeutics responsive to the inflammatory microenvironment hold great potential for the management of vascular restenosis by selectively releasing drug molecules at the inflamed sites.
