Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles.

Federica Vurro,Maria Grazia Romanelli,Massimiliano Perduca,Silvia Mannucci,Alberto Sola-Leyva,Guillermo R Iglesias,María P Carrasco-Jiménez,Laura Calderan,Concepcion Jimenez-Lopez,Manuela Malatesta,Marco Gerosa,Ylenia Jabalera,Alessandro Romeo,Giulia Glorani

doi:10.3390/nano11030766

Abstract

Magnetococcus marinus magnetosome-associated protein MamC, expressed as recombinant, has been proven to mediate the formation of novel biomimetic magnetic nanoparticles (BMNPs) that are successful drug nanocarriers for targeted chemotherapy and hyperthermia agents. These BMNPs present several advantages over inorganic magnetic nanoparticles, such as larger sizes that allow the former to have larger magnetic moment per particle, and an isoelectric point at acidic pH values, which allows both the stable functionalization of BMNPs at physiological pH value and the molecule release at acidic (tumor) environments, simply based on electrostatic interactions. However, difficulties for BMNPs cell internalization still hold back the efficiency of these nanoparticles as drug nanocarriers and hyperthermia agents. In the present study we explore the enhanced BMNPs internalization following upon their encapsulation by poly (lactic-co-glycolic) acid (PLGA), a Food and Drug Administration (FDA) approved molecule. Internalization is further optimized by the functionalization of the nanoformulation with the cell-penetrating TAT peptide (TATp). Our results evidence that cells treated with the nanoformulation [TAT-PLGA(BMNPs)] show up to 80% more iron internalized (after 72 h) compared to that of cells treated with BMNPs (40%), without any significant decrease in cell viability. This nanoformulation showing optimal internalization is further characterized. In particular, the present manuscript demonstrates that neither its magnetic properties nor its performance as a hyperthermia agent are significantly altered due to the encapsulation. In vitro experiments demonstrate that, following upon the application of an alternating magnetic field on U87MG cells treated with BMNPs and TAT-PLGA(BMNPs), the cytotoxic effect of BMNPs was not affected by the TAT-PLGA enveloping. Based on that, difficulties shown in previous studies related to poor cell uptake of BMNPs can be overcome by the novel nanoassembly described here.

Highlights

Directed chemotherapy has emerged as a promising alternative to systematic treatments, allowing the selective delivery of the therapeutic agent to the target, reducing undesirable secondary effects
The first dimensional characterization was performed by dynamic light scattering (DLS), and AFM was used to further characterize their surface (Figure S4) and dimensional properties (Table S1)
The internalization of TAT-poly (lactic-co-glycolic) acid (PLGA)(BMNPs) was always greater, up to 80% more iron internalized, demonstrating the ability of that moiety to ease or induce the internalization of the nanoformulation in the cells

Summary

Introduction

Directed chemotherapy has emerged as a promising alternative to systematic treatments, allowing the selective delivery of the therapeutic agent to the target, reducing undesirable secondary effects. The directed chemotherapy allows the localized in situ combination of several therapeutic treatments [1]. In this scenario, choosing an optimal carrier becomes crucial. Within the broad range of nanocarriers so far studied, magnetic nanoparticles have become attractive candidates. On one hand, their nano scale size makes them display a larger surface area that allows them to carry relatively large amounts of the relevant molecule. Their magnetic properties allow an external guidance and/or concentration at the target site plus the combination of therapies, such as targeted drug delivery and magnetic hyperthermia [2,3,4,5]

Methods

Results

Conclusion