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Differences in surface chemistry of iron oxide nanoparticles result in different routes of internalization.

ABSTRACT: The efficient entry of nanotechnology-based pharmaceuticals into target cells is highly desired to reach high therapeutic efficiency while minimizing the side effects. Despite intensive research, the impact of the surface coating on the mechanism of nanoparticle uptake is not sufficiently understood yet. Herein, we present a mechanistic study of cellular internalization pathways of two magnetic iron oxide nanoparticles (MNPs) differing in surface chemistry into A549 cells. The MNP uptake was investigated in the presence of different inhibitors of endocytosis and monitored by spectroscopic and imaging techniques. The results revealed that the route of MNP entry into cells strongly depends on the surface chemistry of the MNPs. While serum bovine albumin-coated MNPs entered the cells via clathrin-mediated endocytosis (CME), caveolin-mediated endocytosis (CavME) or lipid rafts were preferentially involved in the internalization of polyethylene glycol-coated MNPs. Our data indicate that surface engineering can contribute to an enhanced delivery efficiency of nanoparticles.

SUBMITTER: Svitkova B

PROVIDER: S-EPMC8008094 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Despite the lifesaving medical discoveries of the last century, there is still an urgent need to improve the curative rate and reduce mortality in many fatal diseases such as cancer. One of the main requirements is to find new ways to deliver therapeutics/drugs more efficiently and only to affected tissues/organs. An exciting new technology is nanomaterials which are being widely investigated as potential nanocarriers to achieve localized drug delivery that would improve therapy and reduce adverse drug side effects. Among all the nanocarriers, iron oxide nanoparticles (IONPs) are one of the most promising as, thanks to their paramagnetic/superparamagnetic properties, they can be easily modified with chemical and biological functions and can be visualized inside the body by magnetic resonance imaging (MRI), while delivering the targeted therapy. Therefore, iron oxide nanoparticles were produced here with a novel method and their properties for potential applications in both diagnostics and therapeutics were investigated. The novel method involves production of free standing IONPs by inert gas condensation via the Mantis NanoGen Trio physical vapor deposition system. The IONPs were first sputtered and deposited on plasma cleaned, polyethylene glycol (PEG) coated silicon wafers. Surface modification of the cleaned wafer with PEG enabled deposition of free-standing IONPs, as once produced, the soft-landed IONPs were suspended by dissolution of the PEG layer in water. Transmission electron microscopic (TEM) characterization revealed free standing, iron oxide nanoparticles with size < 20 nm within a polymer matrix. The nanoparticles were analyzed also by Atomic Force Microscope (AFM), Dynamic Light Scattering (DLS) and NanoSight Nanoparticle Tacking Analysis (NTA). Therefore, our work confirms that inert gas condensation by the Mantis NanoGen Trio physical vapor deposition sputtering at room temperature can be successfully used as a scalable, reproducible process to prepare free-standing IONPs. The PEG- IONPs produced in this work do not require further purification and thanks to their tunable narrow size distribution have potential to be a powerful tool for biomedical applications.

Project description:Nanomaterial based drug delivery systems allow for the independent tuning of the surface chemical and physical properties that affect their biodistribution in vivo and the therapeutic payloads that they are intended to deliver. Additionally, the added therapeutic and diagnostic value of their inherent material properties often provides extra functionality. Iron based nanomaterials with their magnetic properties and easily tailorable surface chemistry are of particular interest as model systems. In this study the core radius of the iron oxide nanoparticles (NPs) was 14.08 ± 3.92 nm while the hydrodynamic radius of the NPs, as determined by Dynamic Light Scattering (DLS), was between 90-110 nm. In this study, different approaches were explored to create radiolabeled NPs that are stable in solution. The NPs were functionalized with polycarboxylate or polyamine surface functional groups. Polycarboxylate functionalized NPs had a zeta potential of -35 mV and polyamine functionalized NPs had a zeta potential of +40 mV. The polycarboxylate functionalized NPs were chosen for in vivo biodistribution studies and hence were radiolabeled with (14)C, with a final activity of 0.097 nCi mg(-1) of NPs. In chronic studies, the biodistribution profile is tracked using low level radiolabeled proxies of the nanoparticles of interest. Conventionally, these radiolabeled proxies are chemically similar but not chemically identical to the non-radiolabeled NPs of interest. This study is novel as different approaches were explored to create radiolabeled NPs that are stable, possess a hydrodynamic radius of <100 nm and most importantly they exhibit an identical surface chemical functionality as their non-radiolabeled counterparts. Identical chemical functionality of the radiolabeled probes to the non-radiolabeled probes was an important consideration to generate statistically similar biodistribution data sets using multiple imaging and detection techniques. The radiolabeling approach described here is applicable to the synthesis of a large class of nanomaterials with multiple core and surface functionalities. This work combined with the biodistribution data suggests that the radiolabeling schemes carried out in this study have broad implications for use in pharmacokinetic studies for a variety of nanomaterials.

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Differences in surface chemistry of iron oxide nanoparticles result in different routes of internalization.

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