Waterborne polyurethane magnetic nanomicelles with magnetically governed functions for breast cancer therapy

Athar Mahdieh; Hamid Yeganeh; Hamidreza Motasadizadeh; Effat Nekoueifard; Samane Maghsoudian; Mohammad Hossein Ghahremani; Bo Nyström; Rassoul Dinarvand

doi:10.1016/j.ijpharm.2023.123356

Waterborne polyurethane magnetic nanomicelles with magnetically governed functions for breast cancer therapy

Int J Pharm. 2023 Oct 15:645:123356. doi: 10.1016/j.ijpharm.2023.123356. Epub 2023 Sep 3.

Authors

Athar Mahdieh¹, Hamid Yeganeh², Hamidreza Motasadizadeh³, Effat Nekoueifard⁴, Samane Maghsoudian³, Mohammad Hossein Ghahremani⁵, Bo Nyström⁶, Rassoul Dinarvand⁷

Affiliations

¹ Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14174, Iran; Department of Pharmacy, Section for Pharmaceutics and Social Pharmacy, University of Oslo, N-0316, Oslo, Norway.
² Iran Polymer and Petrochemical Institute, P.O. Box: 14965-115, Tehran, Iran. Electronic address: h.yeganeh@ippi.ac.ir.
³ Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14174, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14174, Iran.
⁴ Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14174, Iran; Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
⁵ Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
⁶ Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern N-0315, Oslo, Norway.
⁷ Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14174, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14174, Iran; Leicester School of Pharmacy, De Montfort University, Leicester, United Kingdom. Electronic address: dinarvand@tums.ac.ir.

PMID: 37661033
DOI: 10.1016/j.ijpharm.2023.123356

Abstract

Drug delivery strategies aim to maximize a drug's therapeutic efficiency by increasing the drug's concentration at the target site while minimizing delivery to off-target tissues. There is a great deal of interest in using magnetic nanoparticles in combination with applied magnetic fields to selectively control drug accumulation and release in target tissue while minimizing effects on other tissues. In this study, a magnetic targeted drug delivery system based on waterborne polyurethane nanomicelles was prepared by encapsulating hydrophobic doxorubicin (DOX, model drug) and hydrophobic oleic acid-superparamagnetic nanoparticles (SPION-OA) into the hydrophobic core of waterborne polyurethane micelles (CPUM) using the solvent evaporation method. The prepared drug-loaded magnetomicelles (CPUM-DOX-SPION) had a spherical shape with an average diameter of 158 nm. The magnetomicelles showed superparamagnetic properties with excellent magnetic resonance imaging (MRI) contrast effects and T₂ relaxation in vitro. In the absence and presence of a magnetic field, the cytocompatibility and cellular uptake of the samples were assessed by MTT assay and flow cytometry, respectively, and the cells were imaged with a confocal microscope. Application of the magnetic field increased cellular cytotoxicity and cellular uptake in association with improved DOX delivery. In addition, the in vivo study of tumor volume showed that tumor growth of the mice group treated with CPUM-DOX-SPION in the presence of an external magnetic field was significantly retarded, with no apparent loss of body weight, compared with the same magnetomicelles in the absence of the magnetic field and with free DOX at the same dose. Moreover, the in vivo MRI experiment indicated the potential of these magnetomicelles as a probe in MRI diagnosis for tumor targeting, and the results showed that magnetically guided delivery of CPUM-SPION magnetomicelles into tumors could significantly improve the targeting efficacy. All the results suggest that the prepared novel magnetomicelles will be promising theranostic systems for effective magnetically guided delivery of chemotherapeutic agents and image-guided personalized medicine.

Keywords: Cancer theranostic systems; Drug delivery systems; Magnetic resonance imaging; Magnetic tumor targeting; Magnetomicelles; Superparamagnetic iron oxide nanoparticles; Waterborne polyurethane.