Submicron Patterning of Polymer Brushes: An Unexpected Discovery from Inkjet Printing of Polyelectrolyte Macroinitiators.

Using an electrostatic-based super inkjet printer we report the high-resolution deposition of polyelectrolyte macroinitiators and subsequent polymer brush growth using SI-ARGET-ATRP. We go on to demonstrate for the first time a submicron patterning phenomenon through the addition of either a like charged polyelectrolyte homopolymer or through careful control of ionic strength. As a result patterning of polymer brushes down to ca. 300 nm is reported. We present a possible mechanistic model and consider how this may be applied to other polyelectrolyte-based systems as a general method for submicron patterning.

Lenghty reverse poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) polymeric micelles and gels for sustained release of antifungal drugs.

In this work, we present a detailed study of the potential application of polymeric micelles and gels of four different reverse triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) copolymers (BOnEOmBOn, where n denotes the respective block lengths), specifically BO8EO90BO8, BO14EO378BO14, BO20EO411BO20 and BO21EO385BO21, as effective drug transport nanocarriers. In particular, we tested the use of this kind of polymeric nanostructures as reservoirs for the sustained delivery of the antifungals griseofulvin and fluconazole for oral and topical administration. Polymeric micelles and gels formed by these copolymers were shown to solubilize important amounts of these two drugs and to have a good stability in physiologically relevant conditions for oral or topical administration. These polymeric micellar nanocarriers were able to release drugs in a sustained manner, being the release rate slower as the copolymer chain hydrophobicity increased. Different sustained drug release profiles were observed depending on the medium conditions. Gel nanocarriers were shown to display longer sustained release rates than micellar formulations, with the existence of a pulsatile-like release mode under certain solution conditions as a result of their inner network structure. Certain bioadhesive properties were observed for the polymeric physical gels, being moderately tuned by the length and hydrophobicity of the polymeric chains. Furthermore, polymeric gels and micelles showed activity against the yeast Candida albicans and the mould demartophytes (Trichophyton rubrum and Microsporum canis) and, thus, may be useful for the treatment of different cutaneous fungal infections.

Analysis of the influence of synthetic paramaters on the structure and physico-chemical properties of non-spherical iron oxide nanocrystals and their biological stability and compatibility.

In this work, we analyzed the effects of subtle changes in the synthetic conditions and synthetic parameters on the resulting size, shape, monodispersity, crystallinity and magnetic properties of iron oxide nanocrystals (IONCs) obtained through a modified one pot method for the production of mainly cubic-shaped nanoparticles (NPs). Cubic, octahedral and cuboctahedral shapes with different sizes and monodispersity could be obtained by slightly changing the stabilizer/precursor molar ratio, the precursor concentration, the reaction time and temperature and/or the heating rate. Their physical properties were evaluated using high-resolution transmission electron microscopy (HRTEM), X-ray powder diffraction (XRD), selected-area electron diffraction (SAED) and a superconducting quantum interference (SQUID) device. It was found that monodisperse cubic nanocrystals from ca. 25 to 94 nm could be obtained either by changing the precursor concentration, the heating rate or the reaction time. These cubic nanocrystals were ferrimagnetic in the whole temperature rage analyzed, with saturation magnetization values even larger than those of bulk magnetite. In addition, slightly truncated octahedral NPs could be achieved at relatively large heating ramp rates, whereas cubooctahedral NPs were derived by simply increasing the stabilizer/precursor molar ratio. The saturation magnetization of both types of NPs was slightly lower than the cubic ones, but they were still ferrimagnetic in the whole temperature range analyzed. Moreover, transfer to aqueous solution was possible by a ligand exchange with dimercaptosuccinic acid (DMSA) providing, at the same time, chemical groups for additional functionalization if required. The DMSA-coated cubic IONCs were fairly stable in culture medium, allowing their internalization by different cell types. The NPs inside the cells were located in the cytoplasm and most of them showed a perinuclear distribution. Moreover, a great cytocompatibility in a large range of particle concentrations was observed without the induction of morphological changes in the cultured cells.

Simple control of surface topography of gold nanoshells by a surfactant-less seeded-growth method.

We report the synthesis of branched gold nanoshells (BGNS) through a seeded-growth surfactant-less method. This was achieved by decorating chitosan-Pluronic F127 stabilized poly(lactic-co-gycolic) acid nanoparticles (NPs) with Au seeds (NP-seed), using chitosan as an electrostatic self-assembling agent. Branched shells with different degrees of anisotropy and optical response were obtained by modulating the ratios of HAuCl4/K2CO3 growth solution, ascorbic acid (AA) and NP-seed precursor. Chitosan and AA were crucial in determining the BGNS size and structure, acting both as coreductants and structure directing growth agents. Preliminary cytotoxicity experiments point to the biocompatibility of the obtained BGNS, allowing their potential use in biomedical applications. In particular, these nanostructures with "hybrid" compositions, which combine the features of gold nanoshells and nanostars showed a better performance as surface enhanced Raman spectroscopy probes in detecting intracellular cell components than classical smoother nanoshells.

Polymeric-gold nanohybrids for combined imaging and cancer therapy.

Here, the use of folic acid (FA)-functionalized, doxorubicin (DOXO)/superparamagnetic iron oxide nanoparticles (SPION)-loaded poly(lactic-co-glycolic acid) (PLGA)-Au porous shell nanoparticles (NPs) as potential nanoplatforms is reported for targeted multimodal chemo- and photothermal therapy combined with optical and magnetic resonance imaging in cancer. These polymeric-gold nanohybrids (PGNH) are produced by a seeded-growth method using chitosan as an electrostatic "glue" to attach Au seeds to DOXO/SPION-PLGA NPs. In order to determine their potential as theranostic nanoplatforms, their physicochemical properties, cellular uptake, and photothermal and chemotherapeutic efficiencies are tested in vitro using a human cervical cancer (HeLa) cell line. The present NPs show a near-infrared (NIR)-light-triggered release of cargo molecules under illumination and a great capacity to induce localized cell death in a well-focused region. The functionalization of the PGNH NPs with the targeting ligand FA improves their internalization efficiency and specificity. Furthermore, the possibility to guide the PGNH NPs to cancer cells by an external magnetic field is also proven in vitro, which additionally increases the cellular uptake and therapeutic efficiency.

Fluorescent drug-loaded, polymeric-based, branched gold nanoshells for localized multimodal therapy and imaging of tumoral cells.

Here we report the synthesis of PLGA/DOXO-core Au-branched shell nanostructures (BGNSHs) functionalized with a human serum albumin/indocyanine green/folic acid complex (HSA-ICG-FA) to configure a multifunctional nanotheranostic platform. First, branched gold nanoshells (BGNSHs) were obtained through a seeded-growth surfactant-less method. These BGNSHs were loaded during the synthetic process with the chemotherapeutic drug doxorubicin, a DNA intercalating agent and topoisomerase II inhibitior. In parallel, the fluorescent near-infrared (NIR) dye indocyanine green (ICG) was conjugated to the protein human serum albumin (HSA) by electrostatic and hydrophobic interactions. Subsequently, folic acid was covalently attached to the HSA-ICG complex. In this way, we created a protein complex with targeting specificity and fluorescent imaging capability. The resulting HSA-ICG-FA complex was adsorbed to the gold nanostructures surface (BGNSH-HSA-ICG-FA) in a straightforward incubation process thanks to the high affinity of HSA to gold surface. In this manner, BGNSH-HSA-ICG-FA platforms were featured with multifunctional abilities: the possibility of fluorescence imaging for diagnosis and therapy monitoring by exploiting the inherent fluorescence of the dye, and a multimodal therapy approach consisting of the simultaneous combination of chemotherapy, provided by the loaded drug, and the potential cytotoxic effect of photodynamic and photothermal therapies provided by the dye and the gold nanolayer of the hybrid structure, respectively, upon NIR light irradiation of suitable wavelength. The combination of this trimodal approach was observed to exert a synergistic effect on the cytotoxicity of tumoral cells in vitro. Furthermore, FA was proved to enhance the internalization of nanoplatform. The ability of the nanoplatforms as fluorescence imaging contrast agents was tested by preliminary analyzing their biodistribution in vivo in a tumor-bearing mice model.