Vurro Federica, Jabalera Ylenia, Mannucci Silvia, Glorani Giulia, Sola-Leyva Alberto, Gerosa Marco, Romeo Alessandro, Romanelli Maria Grazia, Malatesta Manuela, Calderan Laura, Iglesias Guillermo R, Carrasco-Jiménez María P, Jimenez-Lopez Concepcion, Perduca Massimiliano
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy.
Department of Microbiology, Faculty of Sciences, University of Granada, 18071 Granada, Spain.
Nanomaterials (Basel). 2021 Mar 18;11(3):766. doi: 10.3390/nano11030766.
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.
磁小体相关蛋白MamC以重组形式表达，已被证明可介导新型仿生磁性纳米颗粒（BMNP）的形成，这些纳米颗粒是用于靶向化疗的成功药物纳米载体和热疗剂。与无机磁性纳米颗粒相比，这些BMNP具有几个优点，例如更大的尺寸使前者每个颗粒具有更大的磁矩，以及在酸性pH值下的等电点，这使得BMNP在生理pH值下能够稳定功能化，并基于静电相互作用在酸性（肿瘤）环境中释放分子。然而，BMNP进入细胞的困难仍然阻碍了这些纳米颗粒作为药物纳米载体和热疗剂的效率。在本研究中，我们探索了聚（乳酸-乙醇酸）（PLGA）（一种美国食品药品监督管理局（FDA）批准的分子）包裹后BMNP内化的增强情况。通过用细胞穿透TAT肽（TATp）对纳米制剂进行功能化，进一步优化了内化过程。我们的结果表明，与用BMNP处理的细胞（40%）相比，用纳米制剂[TAT-PLGA（BMNP）]处理的细胞在72小时后内化的铁多80%，且细胞活力没有显著下降。对这种显示出最佳内化效果的纳米制剂进行了进一步表征。特别是，本手稿表明，由于包裹，其磁性和作为热疗剂的性能均未发生显著改变。体外实验表明，在用BMNP和TAT-PLGA（BMNP）处理的U87MG细胞上施加交变磁场后，BMNP的细胞毒性作用不受TAT-PLGA包膜的影响。基于此，本文描述的新型纳米组装体可以克服先前研究中显示的与BMNP细胞摄取不良相关的困难。
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