1,2-Dimyristoyl-sn-glycero-3-phosphocholine promotes the adhesion of nanoparticles to bio-membranes and transport in rat brain.

Dong Han,Boning Yang,Junfeng Wang,Liping Wang,Baolin Zhang,Yuntao Peng,Jianghui Dong

doi:10.1039/d1ra01737c

Abstract

1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) coated on the surface of superparamagnetic iron oxide nanoparticles (SPIONs) has advantages in neurotherapy and drug delivery. In this study, the surface of polyvinylpyrrolidone (PVP)-SPIONs was modified with DMPC, then PVP-SPIONs and DMPC/PVP-SPIONs were co-incubated with rat adrenal pheochromocytoma (PC-12) cells to observe the effect of DMPC on the distribution of SPIONs in cells, and further PVP-SPIONs and DMPC/PVP-SPIONs were implanted into the substantia nigra of Sprague-Dawley (SD) rats by stereotaxic injection, and the brain tissues were removed at both twenty-four hours and seven days after injection. The distribution and transport of nanoparticles in the substantia nigra in vivo were explored in these different time periods. The results show that DMPC/PVP-SPIONs were effectively distributed on the membranes of axons, as well as dendritic and myelin sheaths. The attachment of nanoparticles to bio-membranes in the brain could result from similar phospholipid structures of DMPC and the membranes. In addition, DMPC/PVP-SPIONs were transported in the brain faster than those without DMPC. In vitro experiments found that DMPC/PVP-SPIONs enter cells more easily. These characteristics of iron oxide nanoparticles that are modified by phospholipids lead to potential applications in drug delivery or activating neuron membrane channels.

Highlights

Parkinson's disease (PD) is a chronic, neurodegenerative disease, usually caused by the degeneration or death of dopaminergic neurons in the substantia nigra of the brain, causing abnormal motor function and leading to striatal dopamine (DA) de ciency
The surface of polyvinylpyrrolidone (PVP)-superparamagnetic iron oxide nanoparticles (SPIONs) was modified with DMPC, PVP-SPIONs and DMPC/PVPSPIONs were co-incubated with rat adrenal pheochromocytoma (PC-12) cells to observe the effect of DMPC on the distribution of SPIONs in cells, and further PVP-SPIONs and DMPC/PVP-SPIONs were implanted into the substantia nigra of Sprague-Dawley (SD) rats by stereotaxic injection, and the brain tissues were removed at both twenty-four hours and seven days after injection
The results show that DMPC/PVP-SPIONs were effectively distributed on the membranes of axons, as well as dendritic and myelin sheaths

Summary

Introduction

Polymer materials coated on SPIONs can facilitate colloid stability and provide functional groups, such as terminal amines or carboxyl groups, for the design of multifunctional SPIONs for a range of applications.[1,2,10] Suitable SPIONs modi ed with a functional molecule help to establish an effective connection between SPIONs and biological systems.[11,12,13] For example, Mannix et al.[14] reported that superparamagnetic beads covered by multivalent integrin ligands linked to a single integrin receptor on the membrane surface and agglomerated into clusters were able to activate signal transduction in the presence of a magnetic eld. There is a report that tail-veininjected Tween-80 surface-modi ed monodispersed SPIONs. Paper moved across the intact blood–brain barrier (BBB) of rats under a magnetic eld.[15]. Phospholipids, integral components of cell membranes, are composed of polar head groups and nonpolar hydrocarbon tails.[16] the use of phospholipids as a surface modi er can facilitate the synthesis of biocompatible nanomaterials and cause the nanoparticles to target the bio-membrane. 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) is a long double carbon chain.[17] It can be used as a functional molecule for targeting cell membranes due to its good biocompatibility, biodegradability, the similarity with the cell membrane structures, and low immunological responses.[18] Poly(vinylpyrrolidone) (PVP) is an amphiphilic polymer which is able to inhibit protein adsorption onto surfaces. By comparing the results with extracorporeal cell uptake, the distribution and transportation process of PVP-SPIONs and DMPC/PVP-SPIONs were investigated

Materials and methods

Results and discussion

Conclusions