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Lipophilic NO-Driven Nanomotors as Drug Balloon Coating for the Treatment of Atherosclerosis
Authors:Xueting Tang  Lin Chen  Ziyu Wu  Yazhou Li  Jiaqi Zeng  Wentao Jiang  Wenzhi Lv  Mimi Wan  Chun Mao  Min Zhou
Affiliation:1. Department of Vascular Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008 China

National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023 China;2. National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, 210023 China;3. Department of Vascular Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008 China;4. Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210046 China;5. College of Chemistry and Chemical Engineering, Qiannan Normal University for Nationalities, Duyun, 558000 China

Abstract:Drug-coated balloons (DCB) intervention is an important approach for the treatment of atherosclerosis (AS). However, this therapeutic approach has the drawbacks of poor drug retention and penetration at the lesion site. Here, a lipophilic drug-loaded nanomotor as a modified balloon coating for the treatment of AS is reported. First, a lipophilic nanomotor PMA-TPP/PTX loaded with drug PTX and lipophilic triphenylphosphine (TPP) compounds is synthesized. The PMA-TPP/PTX nanomotors use nitric oxide (NO) as the driving force, which is produced from the reaction between arginine on the motor substrate and excess reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) in the AS microenvironment. The final in vitro and in vivo experimental results confirm that the introduction of the lipophilic drug-loaded nanomotor technology can greatly enhance the drug retention and permeability in atherosclerotic lesions. In particular, NO can also play an anti-AS role in improving endothelial cell function and reducing oxidative stress. The chemotherapeutic drug PTX loaded onto the nanomotors can inhibit cell division and proliferation, thereby exerting the effect of inhibiting vascular intimal hyperplasia, which is helpful for the multiple therapies of AS. Using nanomotor technology to solve cardiovascular diseases may be a promising research direction.
Keywords:atherosclerosis  balloons  drug coating  nanomotors  treatments
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