The Use of Magnetic Nanoparticles to Alter Primary Cilia Structure and Function

Abstract

Primary cilia are non‐motile cell organelles with sensory functions. Abnormal cilia structure or function results in disorders, collectively termed as ciliopathies. Ciliopathies include an expanding spectrum of cardiovascular diseases, including hypertension. Microenvironment has directly implicated in an early stage of ciliopathy. Thus, the next nano‐material advances for a cilia‐targeted therapy or ciliotherapy are a desirable approach to treat ciliopathies. We report here that we have generated cilia‐targeted iron oxide (Fe2O3) nanoparticles that offer a new prototype in ciliotherapy. Live‐imaging of single‐cell‐single‐cilium analysis confirmed that the magnetic nanoparticles specifically targeted to primary cilia, making it possible to remotely control the movement and function of cilia with the external magnetic field. When these nanoparticles were loaded with fenoldopam, selected as a candidate drug prototype, the magnetic field accelerated the release of fenoldopam faster than a standard diffusion. A more sustained increase in cytosolic and intraciliary calcium (Ca2+) signaling and release of nitric oxide (NO) were observed only when magnetic field was applied. Importantly, the cardiovascular phenotypes in the ciliopathy models were improved with magnetic field. Our studies suggest that nanoparticles can be used to alter molecular and mechanical property of primary cilia.Support or Funding InformationThis work was supported by the National Institute of Health (HL131577), Congressionally Directed Medical Research Program (PR130153) and American Heart association (19IPLOI34730020)