Structural Transformation of Coassembled Fmoc-Protected Aromatic Amino Acids to Nanoparticles

Materials made of assembled biomolecules such as amino acids have drawn much attention during the past decades. Nevertheless, research on the relationship between the chemical structure of building block molecules, supramolecular interactions, and self-assembled structures is still necessary. Herein, the self-assembly and the coassembly of fluorenylmethoxycarbonyl (Fmoc)-protected aromatic amino acids (tyrosine, tryptophan, and phenylalanine) were studied. The individual self-assembly of Fmoc-Tyr-OH and Fmoc-Phe-OH in water formed nanofibers, while Fmoc-Trp-OH self-assembled into nanoparticles. Moreover, when Fmoc-Tyr-OH or Fmoc-Phe-OH was coassembled with Fmoc-Trp-OH, the nanofibers were transformed into nanoparticles. UV–vis spectroscopy, Fourier transform infrared spectroscopy, and fluorescence spectroscopy were used to investigate the supramolecular interactions leading to the self-assembled architectures. π–π stacking and hydrogen bonding were the main driving forces leading to the self-assembly of Fmoc-Tyr-OH and Fmoc-Phe-OH forming nanofibers. Further, a mechanism involving a two-step coassembly process is proposed based on nucleation and elongation/growth to explain the structural transformation. Fmoc-Trp-OH acted as a fiber inhibitor to alter the molecular interactions in the Fmoc-Tyr-OH or Fmoc-Phe-OH self-assembled structures during the coassembly process, locking the coassembly in the nucleation step and preventing the formation of nanofibers. This structural transformation is useful for extending the application of amino acid self- or coassembled materials in different fields. For example, the amino acids forming nanofibers could be applied for tissue engineering, while they could be exploited as drug nanocarriers when they form nanoparticles

Carbon Nanotube Degradation in Macrophages: Live Nanoscale Monitoring and Understanding of Biological Pathway

Despite numerous applications, the cellular-clearance mechanism of multiwalled carbon nanotubes (MWCNTs) has not been clearly established yet. Previous <i>in vitro</i> studies showed the ability of oxidative enzymes to induce nanotube degradation. Interestingly, these enzymes have the common capacity to produce reactive oxygen species (ROS). Here, we combined material and life science approaches for revealing an intracellular way taken by macrophages to degrade carbon nanotubes. We report the <i>in situ</i> monitoring of ROS-mediated MWCNT degradation by liquid-cell transmission electron microscopy. Two degradation mechanisms induced by hydroxyl radicals were extracted from these unseen dynamic nanoscale investigations: a non-site-specific thinning process of the walls and a site-specific transversal drilling process on pre-existing defects of nanotubes. Remarkably, similar ROS-induced structural injuries were observed on MWCNTs after aging into macrophages from 1 to 7 days. Beside unraveling oxidative transformations of MWCNT structure, we elucidated an important, albeit not exclusive, biological pathway for MWCNT degradation in macrophages, involving NOX₂ complex activation, superoxide production, and hydroxyl radical attack, which highlights the critical role of oxidative stress in cellular processing of MWCNTs

Intercellular Carbon Nanotube Translocation Assessed by Flow Cytometry Imaging

The fate of carbon nanotubes in the organism is still controversial. Here, we propose a statistical high-throughput imaging method to localize and quantify functionalized multiwalled carbon nanotubes in cells. We give the first experimental evidence of an intercellular translocation of carbon nanotubes. This stress-induced longitudinal transfer of nanomaterials is mediated by cell-released microvesicles known as vectors for intercellular communication. This finding raises new critical issues for nanotoxicology, since carbon nanotubes could be disseminated by circulating extracellular cell-released vesicles and visiting several cells in the course of their passage into the organism

Design of Covalently Functionalized Carbon Nanotubes Filled with Metal Oxide Nanoparticles for Imaging, Therapy, and Magnetic Manipulation

Nanocomposites combining multiple functionalities in one single nano-object hold great promise for biomedical applications. In this work, carbon nanotubes (CNTs) were filled with ferrite nanoparticles (NPs) to develop the magnetic manipulation of the nanotubes and their theranostic applications. The challenges were both the filling of CNTs with a high amount of magnetic NPs and their functionalization to form biocompatible water suspensions. We propose here a filling process using CNTs as nanoreactors for high-yield <i>in situ</i> growth of ferrite NPs into the inner carbon cavity. At first, NPs were formed inside the nanotubes by thermal decomposition of an iron stearate precursor. A second filling step was then performed with iron or cobalt stearate precursors to enhance the encapsulation yield and block the formed NPs inside the tubes. Water suspensions were then obtained by addition of amino groups <i>via</i> the covalent functionalization of the external surface of the nanotubes. Microstructural and magnetic characterizations confirmed the confinement of NPs into the anisotropic structure of CNTs making them suitable for magnetic manipulations and MRI detection. Interactions of highly water-dispersible CNTs with tumor cells could be modulated by magnetic fields without toxicity, allowing control of their orientation within the cell and inducing submicron magnetic stirring. The magnetic properties were also used to quantify CNTs cellular uptake by measuring the cell magnetophoretic mobility. Finally, the photothermal ablation of tumor cells could be enhanced by magnetic stimulus, harnessing the hybrid properties of NP loaded-CNTs