PUBLICATION
Personalized Nanotherapy by Specifically Targeting Cell Organelles To Improve Vascular Hypertension
- Authors
- Pala, R., Mohieldin, A.M., Shamloo, K., Sherpa, R.T., Kathem, S.H., Zhou, J., Luan, Z., Zheng, J.G., Ahsan, A., Nauli, S.M.
- ID
- ZDB-PUB-190625-10
- Date
- 2019
- Source
- Nano Letters 19: 904-914 (Journal)
- Registered Authors
- Keywords
- Cilia targeting, calcium, drug delivery, hypertension, nanoparticles, nitric oxide
- MeSH Terms
-
- Animals
- Antihypertensive Agents/administration & dosage*
- Antihypertensive Agents/pharmacokinetics
- Antihypertensive Agents/therapeutic use
- Cells, Cultured
- Cilia/drug effects
- Cilia/metabolism
- Drug Delivery Systems/methods*
- Fenoldopam/administration & dosage*
- Fenoldopam/pharmacokinetics
- Fenoldopam/therapeutic use
- Gold/chemistry*
- Gold/metabolism
- Hypertension/drug therapy*
- Hypertension/metabolism
- Mice
- Nanomedicine/methods
- Nanoparticles/chemistry*
- Nanoparticles/metabolism
- Polylactic Acid-Polyglycolic Acid Copolymer/chemistry*
- Polylactic Acid-Polyglycolic Acid Copolymer/metabolism
- Precision Medicine/methods
- Swine
- Zebrafish
- PubMed
- 30582331 Full text @ Nano Lett.
Citation
Pala, R., Mohieldin, A.M., Shamloo, K., Sherpa, R.T., Kathem, S.H., Zhou, J., Luan, Z., Zheng, J.G., Ahsan, A., Nauli, S.M. (2019) Personalized Nanotherapy by Specifically Targeting Cell Organelles To Improve Vascular Hypertension. Nano Letters. 19:904-914.
Abstract
Ciliopathies caused by abnormal function of primary cilia include expanding spectrum of kidney, liver, and cardiovascular disorders. There is currently no treatment available for patients with cilia dysfunction. Therefore, we generated and compared two different (metal and polymer) cilia-targeted nanoparticle drug delivery systems (CTNDDS), CT-DAu-NPs and CT-PLGA-NPs, for the first time. These CTNDDS loaded with fenoldopam were further compared to fenoldopam-alone. Live-imaging of single-cell-single-cilium analysis confirmed that CTNDDS specifically targeted to primary cilia. While CTNDDS did not show any advantages over fenoldopam-alone in cultured cells in vitro, CTNDDS delivered fenoldopam more superior than fenoldopam-alone by eliminating the side effect of reflex tachycardia in murine models. Although slow infusion was required for fenoldopam-alone in mice, bolus injection was possible for CTNDDS. Though there were no significant therapeutic differences between CT-DAu-NPs and CT-PLGA-NPs, CT-PLGA-NPs tended to correct ciliopathy parameters closer to normal physiological levels, indicating CT-PLGA-NPs were better cargos than CT-DAu-NPs. Both CTNDDS showed no systemic adverse effect. In summary, our studies provided scientific evidence that existing pharmacological agent could be personalized with advanced nanomaterials to treat ciliopathy by targeting cilia without the need of generating new drugs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping