No abstract

Targeted drug delivery depends on the ability of nanocarriers to reach the target site, which requires the penetration of different biological barriers. Penetration is usually low and slow because of passive diffusion and steric hindrance. Nanomotors (NMs) have been suggested as the next generation of nanocarriers in drug delivery due to their autonomous motion and associated mixing hydrodynamics, especially when acting collectively as a swarm. Here, we explore the concept of enzyme-powered NMs designed as such that they can exert disruptive mechanical forces upon laser irradiation. The urease-powered motion and swarm behavior improve translational movement compared to passive diffusion of state-of-the-art nanocarriers, while optically triggered vapor nanobubbles can destroy biological barriers and reduce steric hindrance. We show that these motors, named Swarm 1, collectively displace through a microchannel blocked with type 1 collagen protein fibers (barrier model), accumulate onto the fibers, and disrupt them completely upon laser irradiation. We evaluate the disruption of the microenvironment induced by these NMs (Swarm 1) by quantifying the efficiency by which a second type of fluorescent NMs (Swarm 2) can move through the cleared microchannel and be taken up by HeLa cells at the other side of the channel. Experiments showed that the delivery efficiency of Swarm 2 NMs in a clean path was increased 12-fold in the presence of urea as fuel compared to when no fuel was added. When the path was blocked with the collagen fibers, delivery efficiency dropped considerably and only depicted a 10-fold enhancement after pretreatment of the collagen-filled channel with Swarm 1 NMs and laser irradiation. The synergistic effect of active motion (chemically propelled) and mechanical disruption (light-triggered nanobubbles) of a biological barrier represents a clear advantage for the improvement of therapies which currently fail due to inadequate passage of drug delivery carriers through biological barriers.

The proton transfer between equimolar amounts of [Cd(H 2 EDTA)(H 2 O)] and 2,6-diaminopurine (Hdap) yielded crystals of the out-of-sphere metal complex H 2 (N3,N7)dap [Cd(HEDTA)(H 2 O)]·H 2 O (1) that was studied by single-crystal X-ray diffraction, thermogravimetry, FT-IR spectroscopy, density functional theory (DFT) and quantum theory of "atoms-in-molecules" (QTAIM) methods. The crystal was mainly dominated by H-bonds, favored by the observed tautomer of the 2,6-diaminopurinium(1+) cation. Each chelate anion was H-bonded to three neighboring cations; two of them were also connected by a symmetry-related anti-parallel π,π-staking interaction. Our results are in clear contrast with that previously reported for H 2 (N1,N9)ade [Cu(HEDTA) (H 2 O)]·2H 2 O (EGOWIG in Cambridge Structural Database (CSD), Hade = adenine), in which H-bonds and π,π-stacking played relevant roles in the anion-cation interaction and the recognition between two pairs of ions, respectively. Factors contributing in such remarkable differences are discussed on the basis of the additional presence of the exocyclic 2-amino group in 2,6-diaminopurinium(1+) ion. Crystals 2020, 10, 304 2 of 15 reported analog of adenine, [Cu(HEDTA)(H 2 O)]·2H 2 O [5,32], was also performed. The H-bonding networks that are established at both faces of H 2 dap were also studied using DFT calculations and the relative strength of each H-bond was estimated using the QTAIM theory. The antiparallel π,π-stacking interactions that were formed between the cations were also studied, focusing on the effect of the counter-ions. Materials and Methods ReagentsH 4 EDTA acid (TCI), Hdap (Alfa Aesar) and CdCO 3 (Alfa Aesar) were used as received. CrystallographyA colorless needle crystal of H 2 dap[Cd(HEDTA)(H 2 O)]·H 2 O (1) was mounted on a glass fiber and used for data collection. Crystal data were collected at 100(2) K, using a Bruker D8 VENTURE PHOTON III-14 diffractometer. Graphite-monochromated MoK(α) radiation (λ = 0.71073 Å) was used throughout. The data were processed with APEX2 [33] and corrected for absorption using SADABS (transmissions factors: 1.000-0.962) [34]. The structure was solved by direct methods using the program SHELXS-2013 [35] and refined by full-matrix least-squares techniques against F 2 using SHELXL-2013 [35]. Positional and anisotropic atomic displacement parameters were refined for all non-hydrogen atoms. Hydrogen atoms were located in difference maps and included as fixed contributions riding on attached atoms with isotropic thermal parameters 1.2/1.5 times those of their carrier atoms. Criteria of a satisfactory complete analysis were the ratios of 'rms' shift to standard deviation less than 0.001 and no significant features in final difference maps. Atomic scattering factors were taken from the International Tables for Crystallography [36]. Molecular graphics were plotted with PLATON [37]. A summary of the crystal data, experimental details and refinement results are listed in Table 1. Crystallographic data for 1 has been deposited in the Cambridg...