One major challenge of nanomedicine is to design nanocarriers that deliver active compounds to a target site, at a sufficient concentration and without premature degradation, in order to maximize the efficiency of the substance while limiting secondary effects. In this context, we have developed colloidal nanovectors based on cyclodextrin (CD) amphiphilic derivatives obtained by an enzymatically-catalyzed transesterification by thermolysin. We have shown that after dissolution in acetone, depending on the length of the grafted alkyl chains, the derivatives had the ability to self-organize in water, forming nanoparticles with various shapes and ultrastructures [Gèze et al., Mater. Sci. Eng. C29 (2009), 458]. The knowledge of the morphology and ultrastructure of these nanovectors is crucial in order to optimize their formulation and lyoavailability.
The present communication focuses on the βCD-C14 derivative, i.e. βCDs (made of 7 glucosyl units) acylated on their secondary face with C14 chains. The resulting nanoparticle suspensions were quench-frozen and observed by cryo-transmission electron microscopy (cryo-TEM). The βCD-C14 particles exhibited tortuous multidomain shapes (Figure 1a) and the corresponding small-angle X-ray scattering (SAXS) pattern collected from a concentrated suspension contained peaks whose distribution was consistent with a columnar hexagonal structure (Figure 1c). Depending on the orientation of the particles in the embedding film of vitreous ice, the cryo-TEM images revealed that some particles consisted of misoriented domains separated by sharp interfaces (Figure 1b). A direct view of the hexagonal organization was obtained when the incident beam was parallel to the columns and grain boundaries with various tilt angles were observed. The analysis of the structure of the grain boundaries was based on the concepts of coincidence site lattice (CSL) and structural units (SUs) frequently used to describe the atomic structure of interfaces in metallic alloy and semiconductor polycrystals [Thibault et al., Mat. Sci. Eng. A 164 (1993), 93-100]. An example of stepped tilt boundary is shown in Figure 2b. Assuming that the repeating motif in each grain corresponds to the projection of hollow columns made of βCD-C14 molecules (Figure 2a), the boundary was described with a series of SUs differing by the number of neighboring columns (5, 6 or 7), each of them exhibiting a distinct contrast (Figure 2c) To our knowledge, it is the first time that such grain boundaries are observed in nanoparticles of self-organized amphiphilic molecules and described at the nanometric scale.
We thank Agence Nationale de la Recherche (contract #ANR-11-BS10-0007) and Institut de Chimie Moléculaire de Grenoble for financial support, Cyrille Rochas and the French CRG (BM02 beamline) at ESRF for granting beamtime for SAXS experiments, and Delphine Levilly (DPM) for the synthesis of the βCD-C14 derivative.
To cite this abstract:Jean-Luc Putaux, Christine Lancelon-Pin, Luc Choisnard, Annabelle Gèze, Denis Wouessidjewe ; Grain boundaries in nanoparticles made of self-assembled amphiphilic β-cyclodextrins. The 16th European Microscopy Congress, Lyon, France. https://emc-proceedings.com/abstract/grain-boundaries-in-nanoparticles-made-of-self-assembled-amphiphilic-%ce%b2-cyclodextrins/. Accessed: May 26, 2020
EMC Abstracts - https://emc-proceedings.com/abstract/grain-boundaries-in-nanoparticles-made-of-self-assembled-amphiphilic-%ce%b2-cyclodextrins/