Dual stimuli-responsive hollow nanogel spheres serving as an efficient intracellular drug delivery platform were obtained from the spontaneous coassociation of two graft copolymers into the vesicle architecture in aqueous phase. Both copolymers comprise acrylic acid (AAc) and 2-methacryloylethyl acrylate (MEA) units as the backbone and either poly(N-isopropylacrylamide) (PNIPAAm) alone or both PNIPAAm and monomethoxypoly(ethylene glycol) (mPEG) chain segments as the grafts. The assemblies were then subjected to covalent stabilization within vesicle walls with ester-containing cross-links by radical polymerization of MEA moieties, thereby leading to hollow nanogel particles. Taking the advantage of retaining a low quantity of payload within polymer layer-enclosed aqueous chambers through the entire loading process, doxorubicin (DOX) in the external bulk phase can be effectively transported into the gel membrane and bound therein via electrostatic interactions with ionized AAc residues and hydrogen-bond pairings with PNIPAAm grafts at pH 7.4. With the environmental pH being reduced (e.g., from 7.4 to 5.0) at 37 °C, the extensive disruption of AAc/DOX complexes due to the reduced ionization of AAc residues within the gel layer and the pronounced shrinkage of nanogels enable the rapid release of DOX species from drug-loaded hollow nanogels. By contrast, the drug liberation at 4 °C was severally restricted, particularly at pH 7.4 at which the DOX molecules remain strongly bound with ionized AAc residues and PNIPAAm grafts. The in vitro characterizations suggest that the DOX-loaded hollow nanogel particles after being internalized by HeLa cells via endocytosis can rapidly release the payload within acidic endosomes or lysosomes. This will then lead to significant drug accumulation in nuclei (within 1 h) and a cytotoxic effect comparable to free drug. This work demonstrates that the novel DOX-loaded hollow nanogel particles show great promise of therapeutic efficacy for potential anticancer treatment.

Hollow hybrid nanogels were prepared first by the coassembly of the citric acid-coated superparamagnetic iron oxide nanoparticles (SPIONs, 44 wt %) with the graft copolymer (56 wt %) comprising acrylic acid and 2-methacryloylethyl acrylate units as the backbone and poly(ethylene glycol) and poly(N-isopropylacrylamide) as the grafts in the aqueous phase of pH 3.0 in the hybrid vesicle structure, followed by in situ covalent stabilization via the photoinitiated polymerization of MEA residues within vesicles. The resultant hollow nanogels, though slightly swollen, satisfactorily retain their structural integrity while the medium pH is adjusted to 7.4. Confining SPION clusters to such a high level (44 wt %) within the pH-responsive thin gel layer remarkably enhances the transverse relaxivity (r2) and renders the MR imaging highly pH-tunable. For example, with the pH being adjusted from 4.0 to 7.4, the r2 value can be dramatically increased from 138.5 to 265.5 mM(-1) s(-1). The DOX-loaded hybrid nanogels also exhibit accelerated drug release in response to both pH reduction and temperature increase as a result of the substantial disruption of the interactions between drug molecules and copolymer components. With magnetic transport guidance toward the target and subsequent exposure to an alternating magnetic field, this DOX-loaded nanogel system possessing combined capabilities of hyperthermia and stimuli-triggered drug release showed superior in vitro cytotoxicity against HeLa cells as compared to the case with only free drug or hyperthermia alone. This work demonstrates that the hollow inorganic/organic hybrid nanogels hold great potential to serve as a multimodal theranostic vehicle functionalized with such desirable features as the guidable delivery of stimuli-mediated diagnostic imaging and hyperthermia/chemotherapies.

Hans-Joachim Freund opened the discussion of the paper by Alberto Roldan: How is the atomic hydrogen produced on the greigite surface? In the paper (DOI: 10.1039/C5FD00186B) there is no comment whether you studied dissociate hydrogen adsorption.Alberto Roldan answered: We agree with Prof. Freund that we have not studied the hydrogen dissociation on the surface. However, the experiments are carried out on small nanoparticles exposing different surfaces and edges where H 2 molecules dissociate, as DRIFTS tests (not published) have suggested by the formation of reduced carbonated species.Rutger van Santen remarked: According to Wachterhauser, the reactive phase is Mackinawite. This is a layered FeS phase. The S may also have a higher reactivity than that of Greigite. How does the activation of H 2 on Greigite compare with that of Mackinawite, and would the reactivity of S be such that SO groups form in the surface that helps to generate CO? The SO group can have a subsequent reaction with H 2 S to give S 2 , which would help to transform the Mackinawite to pyrite.

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Understanding the interaction of five-membered aromatic heterocycles with Fe(110) surface is crucial for the development of novel inhibitors against the corrosion of iron and steel.Herein, we report a detailed study of the adsorption properties and the bonding mechanism of pyrrole, furan, and thiophene on Fe(110) surface employing density functional theory (DFT) calculations. In the most stable adsorption geometries, we found that the adsorbates lie flat at the hollow site and form chemical bondings with four Fe atoms on Fe(110) surface. The chemisorptions are indicated by large adsorption energies and charge transfers from the surface to the adsorbates. We also found that taking into account vdW corrections in the DFT calculations has a minimal effect on the adsorption geometries whereas it significantly increases the adsorption energies. The energetic and structural analysis reveals large molecular distortions induced by the adsorbate-surface interactions, and among the adsorbates, thiophene experiences the least molecular distortion, thereby having the largest adsorption energy. The electronic structure analysis also reveals that the nature of electronic interaction of pyrrole, furan, and thiophene with Fe(110) surface is due to the strong overlaps of the frontier  and * orbitals of the adsorbates with Fe-3dz 2 and Fe-(3dxz+3dyz) states of the surface. The charge donation and back-donation between the adsorbates and Fe(110) surface were also elucidated by the Bader charge analysis and the charge density difference.