Improved antitumor activity through a tyramidyl maslinic acid derivative. Design and validation as drug-loaded electrospun polymeric nanofibers.

Among the most harmful tumors detected in the human body, such as breast, colon, brain or pancreas, breast (BC) and colorectal cancer (CRC) are the first and third most frequent cancer worldwide, respectively. The current existing chemotherapeutic treatments present serious side effects due to their intravenous administration can induce cytotoxicity in healthy cells. Thus, new treatment methods based on drug-loaded polymeric nanofibers (NFs) have gained significant potential for their use in localized cancer chemotherapy. Here, a deep in vitro comparative analysis between maslinic acid (MA) and a tyramine-maslinic acid (TMA) derivative is initially performed. This analysis includes a proliferation, and a cell cycle assay, and a genotoxicity, antiangiogenic and apoptosis study. Then, the TMA derivative has been incorporated into electrospun polymeric NFs obtaining an implantable dressing material with antitumor activity. Two types of patches containing TMA-loaded polymeric NFs of poly(caprolactone) (PCL), and a mixture of polylactic acid/poly(4-vinylpyridine) (PLA/PVP) were fabricated by the electrospinning technique. The characterization of the drug-loaded NFs showed an encapsulation capacity of 0.027 mg TMA/mg PCL and 0.024 mg TMA/mg PLA/PVP. Then, the cytotoxic activity of both polymeric systems was tested in CRC (T84), BC (MCF-7) and a no tumor (L929) cell lines exposed to TMA-loaded NFs and blank NFs for 48 h. Moreover, cell cycle assay, genotoxicity, angiogenesis and apoptosis tests were carried out to study the mechanism of action of TMA. Blank NFs showed no-toxicity in all cell lines tested and both drug-loaded NFs significantly reduced cell proliferation (relative proliferation of ≈44 % and ≈25 % respectively). Therefore, TMA was less genotoxic than maslinic acid (MA), and reduced VEGFA expression in MCF-7 cells (1.32 and 2.12-fold for MA and TMA respectively). These results showed that TMA-loaded NFs could constitute a promising biocompatible and biodegradable nanoplatform for the local treatment of solid tumors such as CRC or BC.

SPION nanoparticles for delivery of dopaminergic isoquinoline and benzazepine derivatives.

Superparamagnetic iron nanoparticles (SPIONs) have become one of the most useful colloidal systems in nanomedicine. We report here the preparation of new hybrid core@shell systems based on SPION nanoparticles coated with a SiO2 shell (SPION@SiO2) and functionalized with carboxyl groups (SPION@SiO2-COOH). A series of new N-alkylamino- and N-alkylamido-terminated 1-phenyl- tetrahydroisoquinolines (THIQs) and 3-tetrahydrobenzazepines (THBs) derivatives presenting -SMe and -Cl groups, respectively, with potential dopaminergic activity, are synthesized and incorporated to the hybrid system. We include the synthetic details for THIQs and THBs derivatives preparation and investigate the influence of the terminal-functional group as well as the number of carbon atoms linked to THIQ and THB molecules during the coupling to the SPION@SiO2-COOH. Nuclear magnetic resonance (NMR) and electron ionization mass spectrometry (EI-MS) are used to characterize the synthesized THIQs and THBs. High-angle annular dark-field transmission electron microscopy (HAADF-TEM), energy dispersive X-ray transmission electron microscopy (EDX-TEM), and proton high-resolution magic angle spinning NMR spectroscopy1H HRMAS-NMR) are used to confirm the presence of THB and THIQ molecules onto the surface of the nanoparticles. The hybrid SPION@SiO2-THIQ and THB systems show significant activity toward the D2 receptor, reaching Ki values of about 20 nM, thus having potential application in the treatment of central nervous system (CNS) diseases.

Nanoscale Biocompatible Structures Generated from Fluorinated Tripodal Phenylenes on Gold Nanoprisms.

Modification of gold substrates with a stable, uniform and ultrathin layer of biocompatible materials is of tremendous interest for the development of bio-devices. We present the fabrication of hybrid systems consisting of triangular prism gold nanoparticles (Au@NTPs) covalently covered with tripod-shaped oligo(p-phenylenes) featuring trifluoromethyl groups. Their synthesis is accomplished using a biphenyl boronic ester as the key compound. Au@NTPs were prepared through a seedless procedure using 3-butenoic acid and benzyldimethyl ammonium chloride, and modified with aminothiol groups. Coverage of this amine-modified gold substrate with a self-assembled monolayer (SAM) of tripod-shaped molecules is carried out in ethanolic solution. The hybrid system avoids up to 70 % of protein corona formation, and allows unspecific attachment for bulky adsorbates, providing an optimal biosensing platform. Chemical composition and morphology are analyzed by transmission electron microscopy (TEM), UV-visible spectroscopy and field emission scanning electron microscopy (FESEM).

Electrospraying as a Technique for the Controlled Synthesis of Biocompatible PLGA@Ag2S and PLGA@Ag2S@SPION Nanocarriers with Drug Release Capability.

Ag2S nanoparticles are near-infrared (NIR) probes providing emission in a specific spectral range (~1200 nm), and superparamagnetic iron oxide nanoparticles (SPION) are colloidal systems able to respond to an external magnetic field. A disadvantage of Ag2S NPs is the attenuated luminescent properties are reduced in aqueous media and human fluids. Concerning SPION, the main drawback is the generation of undesirable clusters that reduce particle stability. Here, we fabricate biocompatible hybrid nanosystems combining Ag2S NPs and SPION by the electrospraying technique for drug delivery purposes. These nanostructures are composed of poly(lactic-co-glycolic acid) (PLGA) as the polymeric matrix in connection with both Ag2S NPs and SPIONs. Initially, we fabricate a hybrid colloidal nanosystem composed of Ag2S NPs in connection with PLGA (PLGA@Ag2S) by three different routes, showing good photoluminescent (PL) properties with relatively high average decay times. Then, we incorporate SPIONs, obtaining a PLGA polymeric matrix containing both Ag2S NPs and SPION (PLGA@Ag2S@SPION). Interestingly, in this hybrid system, the location of Ag2S NPs and SPIONs depends on the synthesis route performed during electrospraying. After a detailed characterization, we demonstrate the encapsulation and release capabilities, obtaining the kinetic release using a model chemotherapeutic drug (maslinic acid). Finally, we perform in vitro cytotoxicity assays using drug-loaded hybrid systems against several tumor cell lines.

Ionotropic Gelation-Based Synthesis of Chitosan-Metal Hybrid Nanoparticles Showing Combined Antimicrobial and Tissue Regenerative Activities.

The treatment of skin wounds poses significant clinical challenges, including the risk of bacterial infection. In particular due to its antimicrobial and tissue regeneration abilities chitosan (a polymeric biomaterial obtained by the deacetylation of chitin) has received extensive attention for its effectiveness in promoting skin wound repair. On the other hand, due to their intrinsic characteristics, metal nanoparticles (e.g., silver (Ag), gold (Au) or iron oxide (Fe3O4)) have demonstrated therapeutic properties potentially useful in the field of skin care. Therefore, the combination of these two promising materials (chitosan plus metal oxide NPs) could permit the achievement of a promising nanohybrid with enhanced properties that could be applied in advanced skin treatment. In this work, we have optimized the synthesis protocol of chitosan/metal hybrid nanoparticles by means of a straightforward synthetic method, ionotropic gelation, which presents a wide set of advantages. The synthesized hybrid NPs have undergone to a full physicochemical characterization. After that, the in vitro antibacterial and tissue regenerative activities of the achieved hybrids have been assessed in comparison to their individual constituent. As result, we have demonstrated the synergistic antibacterial plus the tissue regeneration enhancement of these nanohybrids as a consequence of the fusion between chitosan and metallic nanoparticles, especially in the case of chitosan/Fe3O4 hybrid nanoparticles.

Scaling Laws in the Diffusive Release of Neutral Cargo from Hollow Hydrogel Nanoparticles: Paclitaxel-Loaded Poly(4-vinylpyridine).

We study the nonequilibrium diffusive release of electroneutral molecular cargo encapsulated inside hollow hydrogel nanoparticles. We propose a theoretical model that includes osmotic, steric, and short-range polymer-cargo attractions to determine the effective cargo-hydrogel interaction, ueff*, and the effective diffusion coefficient of the cargo inside the polymer network, Deff*. Using dynamical density functional theory (DDFT), we investigate the scaling of the characteristic release time, τ1/2, with the key parameters involved in the process, namely, ueff*, Deff*, and the swelling ratio. This effort represents a full study of the problem, covering a broad range of cargo sizes and providing predictions for repulsive and attractive polymer shells. Our calculations show that the release time through repulsive polymer networks scales with q2eßueff*/Deff* for ßueff* ≫ 1. In this case, the cargo molecules are excluded from the shell of the hydrogel. For attractive shells, the polymer retains the cargo molecules on its internal surface and its interior, and the release time grows exponentially with the attraction strength. The DDFT calculations are compared to an analytical model for the mean first passage time, which provides an excellent quantitative description of the kinetics for both repulsive and attractive shells without fitting parameters. Finally, we apply the method to reproduce experimental results on the release of paclitaxel from hollow poly(4-vinylpyridine) nanoparticles and find that the slow release of the drug can be explained in terms of the strong binding attraction between the drug and the polymer.

Magnetically active pNIPAM nanosystems as temperature-sensitive biocompatible structures for controlled drug delivery.

Here, temperature-sensitive hybrid poly(N-isopropylacrylamide) (pNIPAM) nanosystems with magnetic response are synthesised and investigated for controlled release of 5-fluorouracil (5FU) and oxaliplatin (OXA). Initially, magnetic nanoparticles (@Fe3O4) are synthesised by co-precipitation approach and functionalised with acrylic acid (AA), 3-butenoic acid (3BA) or allylamine (AL) as comonomers. The thermo-responsive polymer is grown by free radical polymerisation using N-isopropylacrylamide (NIPAM) as monomer, N,N'-methylenbisacrylamide (BIS) as cross-linker, and 2,2'-azobis(2-methylpropionamidene) (V50) as initiator. We evaluate particle morphology by transmission electron microscopy (TEM) and particle size and surface charge by dynamic light scattering (DLS) and Z-potential (ZP) measurements. These magnetically active pNIPAM@ nanoformulations are loaded with 5-fluorouracil (5FU) and oxaliplatin (OXA) to determine loading efficiency, drug content and release as well as the cytotoxicity against T-84 colon cancer cells. Our results show high biocompatibility of pNIPAM nanoformulations using human blood cells and cultured cells. Interestingly, the pNIPAM@Fe3O4-3BA + 5FU nanoformulation significantly reduces the growth of T-84 cells (57% relative inhibition of proliferation). Indeed, pNIPAM-co-AL@Fe3O4-AA nanosystems produce a slight migration of HCT15 cells in suspension in the presence of an external magnetic field. Therefore, the obtained hybrid nanoparticles can be applied as a promising biocompatible nanoplatform for the delivery of 5FU and OXA in the improvement of colon cancer treatments.

10-Fold Quantum Yield Improvement of Ag2S Nanoparticles by Fine Compositional Tuning.

Ag2S semiconductor nanoparticles (NPs) are near-infrared luminescent probes with outstanding properties (good biocompatibility, optimum spectral operation range, and easy biofunctionalization) that make them ideal probes for in vivo imaging. Ag2S NPs have, indeed, made possible amazing challenges including in vivo brain imaging and advanced diagnosis of the cardiovascular system. Despite the continuous redesign of synthesis routes, the emission quantum yield (QY) of Ag2S NPs is typically below 0.2%. This leads to a low luminescent brightness that avoids their translation into the clinics. In this work, an innovative synthetic methodology that permits a 10-fold increment in the absolute QY from 0.2 up to 2.3% is presented. Such an increment in the QY is accompanied by an enlargement of photoluminescence lifetimes from 184 to 1200 ns. The optimized synthetic route presented here is based on a fine control over both the Ag core and the Ag/S ratio within the NPs. Such control reduces the density of structural defects and decreases the nonradiative pathways. In addition, we demonstrate that the superior performance of the Ag2S NPs allows for high-contrast in vivo bioimaging.

Temperature-Controlled Catalysis by Core-Shell-Satellite AuAg@pNIPAM@Ag Hybrid Microgels: A Highly Efficient Catalytic Thermoresponsive Nanoreactor.

A novel wet-chemical protocol is reported for the synthesis of "temperature-programmable" catalytic colloids consisting of bimetallic core@shell AuAg nanoparticles encapsulated into poly(N-isopropylacrylamide) (pNIPAM) microgels with silver satellites (AgSTs) incorporated within the microgel structure. Spherical AuNPs of 50 nm in diameter are initially synthesized and used for growing a pNIPAM microgel shell with temperature stimulus response. A silver shell is subsequently grown on the Au core by diffusing Ag salt through the hydrophilic pNIPAM microgel (AuAg@pNIPAM microgel). The use of allylamine as a co-monomer during pNIPAM polymerization facilitates the coordination of Ag+ with the NH2 nitrogen lone pair of electrons, which are reduced to Ag seeds (∼14 nm) using a strong reducing agent, obtaining thus AuAg@pNIPAM@Ag hybrid microgels. The two systems are tested as catalysts toward the reduction of 4-nitrophenol (4-Nip) to 4-aminophenol (4-Amp) by NaBH4. Both exhibit extremely sensitive temperature-dependent reaction rate constants, with the highest K1 value of the order of 0.6 L/m2 s, which is one of the highest values ever reported. The presence of plasmonic entities is confirmed by UV-vis spectroscopy. Dynamic light scattering proves the temperature responsiveness in all cases. Transmission electron microscopy and energy-dispersive X-ray (EDX) elemental mapping highlight the monodispersity of the synthesized hybrid nanostructured microgels, as well as their size and metallic composition. The amount of gold and silver in both systems is obtained by thermogravimetric analysis and the EDX spectrum. The reduction reaction kinetics is monitored by UV-vis spectroscopy at different temperatures for both catalytic systems, with the AuAg@pNIPAM@Ag microgels showing superior catalytic performance at all temperatures because of the synergistic effect of the AuAg core and the AgSTs. The principal novelty of this study lies in the "hierarchical" design of the metal-polymer-metal core@shell@satellite nanostructured colloids exhibiting synergistic capabilities of the plasmonic NPs for, among others, temperature-controlled catalytic applications.

Electrospun Nanofibers: Recent Applications in Drug Delivery and Cancer Therapy.

Polymeric nanofibers (NFs) have been extensively reported as a biocompatible scaffold to be specifically applied in several researching fields, including biomedical applications. The principal researching lines cover the encapsulation of antitumor drugs for controlled drug delivery applications, scaffolds structures for tissue engineering and regenerative medicine, as well as magnetic or plasmonic hyperthermia to be applied in the reduction of cancer tumors. This makes NFs useful as therapeutic implantable patches or mats to be implemented in numerous biomedical researching fields. In this context, several biocompatible polymers with excellent biocompatibility and biodegradability including poly lactic-co-glycolic acid (PLGA), poly butylcyanoacrylate (PBCA), poly ethylenglycol (PEG), poly (ε-caprolactone) (PCL) or poly lactic acid (PLA) have been widely used for the synthesis of NFs using the electrospun technique. Indeed, other types of polymers with stimuli-responsive capabilities has have recently reported for the fabrication of polymeric NFs scaffolds with relevant biomedical applications. Importantly, colloidal nanoparticles used as nanocarriers and non-biodegradable structures have been also incorporated by electrospinning into polymeric NFs for drug delivery applications and cancer treatments. In this review, we focus on the incorporation of drugs into polymeric NFs for drug delivery and cancer treatment applications. However, the principal novelty compared with previously reported publications is that we also focus on recent investigations concerning new strategies that increase drug delivery and cancer treatments efficiencies, such as the incorporation of colloidal nanoparticles into polymeric NFs, the possibility to fabricate NFs with the capability to respond to external environments, and finally, the synthesis of hybrid polymeric NFs containing carbon nanotubes, magnetic and gold nanoparticles, with magnetic and plasmonic hyperthermia applicability.

Seeded Growth Synthesis of Gold Nanotriangles: Size Control, SAXS Analysis, and SERS Performance.

We studied the controlled growth of triangular prismatic Au nanoparticles with different beveled sides for surface-enhanced Raman spectroscopy (SERS) applications. First, in a seedless synthesis using 3-butenoic acid (3BA) and benzyldimethylammonium chloride (BDAC), gold nanotriangles (AuNTs) were synthesized in a mixture with gold nanooctahedra (AuNOCs) and separated by depletion-induced flocculation. Here, the influence of temperature, pH, and reducing agent on the reaction kinetics was initially investigated by UV-vis and correlated to the size and yield of AuNT seeds. In a second step, the AuNT size was increased by seed-mediated overgrowth with Au. We show for the first time that preformed 3BA-synthesized AuNT seeds can be overgrown up to a final edge length of 175 nm and a thickness of 80 nm while maintaining their triangular shape and tip sharpness. The NT morphology, including edge length, thickness, and tip rounding, was precisely characterized in dispersion by small-angle X-ray scattering and in dry state by transmission electron microscopy and field-emission scanning electron microscopy. For sensor purposes, we studied the size-dependent SERS performance of AuNTs yielding analytical enhancement factors between 0.9 × 104 and 5.6 × 104 and nanomolar limit of detection (10-8-10-9 M) for 4-mercaptobenzoic acid and BDAC. These results confirm that the 3BA approach allows the fabrication of AuNTs in a whole range of sizes maintaining the NT morphology. This enables tailoring of localized surface plasmon resonances between 590 and 740 nm, even in the near-infrared window of a biological tissue, for use as colloidal SERS sensing agents or for optoelectronic applications.

Au@p4VP core@shell pH-sensitive nanocomposites suitable for drug entrapment.

We synthesize and characterize pH-responsive hybrid nanocomposites with SERS and drug loading applications. This colloidal system is structured by spherical 50 nm Au cores individually coated by a pH-sensitive shell of poly4-vinylpyridine (Au@p4VP). The synthesis of these hybrid nanocomposites is performed in two steps, a first one involves the fabrication of vinyl-functionalized Au nanoparticles, and a second one includes the controlled overgrowth of a p4VP shell by free radical polymerization. As a result, Au@p4VP hybrid systems with a mean diameter ranging from 150 to 57 nm are obtained upon varying the monomer concentration at synthesis. Au@p4VP nanocomposite exhibits pH-response capabilities, confirmed by cryo-TEM analysis, Small Angle X-ray Scattering (SAXS) and Zeta Potential (ZP) measurements at different pH conditions. The Au@p4VP particles also display a controllable swelling response, which depends on the cross-linker density within the polymer. This swelling capability is analyzed by Dynamic Light Scattering (DLS), and UV-vis spectroscopy at different pHs. The pH-responsive capability is here exploited for the chemical entrapment of doxorubicin hydrochloride (Dox) into the polymer network. The presence of this molecule is resolved by Surface Enhanced Raman Spectroscopy (SERS) measurements. The entrapment efficiency of Dox by the Au@p4VP system is determined via NMR spectroscopy of the supernatants.

Tripalmitin nanoparticle formulations significantly enhance paclitaxel antitumor activity against breast and lung cancer cells in vitro.

Paclitaxel (PTX) is one of the drugs of choice in the treatment of breast and lung cancer. However, its severe side effects, including mielosuppression, cardiotoxicity and neurotoxicity, frequently cause treatment to be discontinued. Solid lipid nanoparticles (NPs) of glyceril tripalmitate (tripalmitin) loaded with PTX (Tripalm-NPs-PTX) including modifications by the addition of hexa(ethylene glycol), ß-cyclodextrin and macelignan were developed. All NPs-PTX formulations displayed excellent hemocompatibility and significantly enhanced PTX antitumor activity in human breast (MCF7, MDAMB231, SKBR3 and T47D) and lung (A549, NCI-H520 and NCI-H460) cancer cells. Tripalm-NPs-PTX decreased PTX IC50 by as much as 40.5-fold in breast and 38.8-fold in lung cancer cells and Tripalm-NPs-PTX macelignan inhibited P-glycoprotein in resistant tumor cells. In addition, Tripalm-NPs-PTX significantly decreased the volume of breast and lung multicellular tumor spheroids that mimics in vivo tumor mass. Finally, Tripalm-NPs-PTX decreased the PTX IC50 of cancer stem cells (CSCs) derived from both lung and breast cancer cells (6.7- and 14.9-fold for MCF7 and A549 CSCs, respectively). These results offer a new PTX nanoformulation based on the use of tripalmitin which improves the antitumor activity of PTX and that may serve as an alternative PTX delivery system in breast and lung cancer treatment.

Carbon dots on based folic acid coated with PAMAM dendrimer as platform for Pt(IV) detection.

Carbon quantum dots (CQDs) coated with poly(amidoamine) (PAMAM-NH2) dendrimer are prepared from folic acid and phosphoric acid under a hydrothermal procedure. The obtained nanoparticles are successfully used as fluorescent sensor for Pt(IV) (in the form of chloroplatinate ion). CQDs possess many attractive features including uniform dispersion with average size about 13nm for unmodified particles and, ∼30nm when they are coated with PAMAM-NH2 dendrimer. The synthesized nanoparticles have been characterized by elemental analysis, attenuated total reflectance (ATR), X-ray photoelectron (XPS) and Raman spectroscopies, transmission electron microscopy (TEM), dynamic light scattering (DLS), and steady-state and life-time fluorescence. CQDs are used as fluorescent sensor of Pt(IV) ion in aqueous media showing linear quenching effect of their fluorescence. The results obtained demonstrated a limit of detection of 657nM with an accuracy of the method of 0.13% (as RSD, n=10) and sensitivity of 78nM. Moreover, with the presence of other interference species, good results are obtained when applied in real samples from platinum nanoparticles synthesis. The dissolved platinum ions can be quantified in the range 6-96µM with an accuracy of 2.5%.

Modification of fluorous substrates with oligo(ethylene glycol) via "click" chemistry for long-term resistance of cell adhesion.

In this work perfluorinated substrates fabricated from SiO2 glass slides are modified with oligo(ethylene glycol) (OEG) units for long-term resistance of cell adhesion purposes, based on fluorous interactions and click chemistry. Specifically, fluorous substrates, prepared by treatment of glass slides with 1H, 1H, 2H, 2H-perfluorodecyltrimethoxysilane (FAS17), were coated with ethynyl-OEG-C8F17, followed by covalent attachment of an azido-OEG via copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction. We demonstrate that the resultant surface avoid fibrinogen adsorption and resisted cell adhesion for over 14days. X-ray photoemission spectroscopy (XPS) analysis and contact angle goniometry measurements confirm the presence of the OEG molecules on the fluorous substrates. Bright field optical images show total absence of 3T3 fibroblast cells on the OEG modified fluorinated substrate for 1 and 5days, and a remarkably decrease of cell adhesion at 14days.

Gold Nanorod-pNIPAM Hybrids with Reversible Plasmon Coupling: Synthesis, Modeling, and SERS Properties.

The thermoresponsive optical properties of Au nanorod-doped poly(N-isopropylacrylamide) (Au NR-pNIPAM) microgels with different Au NR payloads and aspect ratios are presented. Since the volume phase transition of pure pNIPAM microgels is reversible, the optical response reversibility of Au NR-pNIPAM hybrids is systematically analyzed. Besides, extinction cross-section and near-field enhancement simulations for Au NR-microgel hybrids are performed using a new numerical method based on the surface integral equation method of moments formulation (M3 solver). Additionally, the Au NR-microgel hybrid systems are expected to serve as excellent broadband surface-enhanced Raman scattering (SERS) substrates due to the temperature-controlled formation of hot spots and the tunable optical properties. The optical enhancing properties related to SERS are tested with three laser lines, evidencing excitation wavelength-dependent efficiency that can be easily controlled by either the aspect ratio (length/width) of the assembled Au NR or by the Au NR payload per microgel. Finally, the SERS efficiency of the prepared Au NR-pNIPAM hybrids is found to be stable for months.

Effect of the cross-linking density on the thermoresponsive behavior of hollow PNIPAM microgels.

We report on the fabrication of thermally responsive hollow pNIPAM particles through the oxidation of the metal core in an Au@pNIPAM system. The selective oxidation of the Au core is achieved by addition of AuCl4(-) to an aqueous dispersion of Au@pNIPAM particles in the presence of cetyltrimethylammonium bromide (CTAB). We fabricate hollow pNIPAM particles with three cross-linking densities (N,N'-methylenebis(acrylamide), BA, at 5%, 10%, and 17.5%). The study of the effect of the amount of BA within the microgel network was performed by dynamic light scattering (DLS), transmission electron microscopy (TEM), and atomic force microscopy (AFM), showing its key role in determining the final hollow structure and thermal response. While the thermal responsiveness is largely achieved at low cross-linking densities, the hollow structure only remains at larger cross-linking densities. This was further confirmed by cryo-TEM analysis of hollow pNIPAM particles below and above the volume phase transition temperature (VPTT). Thus, it clearly shows (i) the shrinking of particle size with the temperature at low cross-linking density and (ii) the dependence of particle size on the amount of cross-linker for the final hollow pNIPAM structure. Observed differences in the hollow pNIPAM structure are attributed to different elastic contributions (Π(elas)), showing higher elasticity for microgels synthesized at lower amount of BA.

Temperature controlled fluorescence on Au@Ag@PNIPAM-PTEBS microgels: effect of the metal core size on the MEF extension.

In this work, we present a novel method to produce thermoresponsive, monodisperse microgels which display temperature-dependent photoluminescence. The system is based on bimetallic cores of Au@Ag encapsulated within thermoresponsive poly(N-isopropylacrylamide) microgels and coated with a photoluminescent polymer (poly[2-(3-thienyl)ethoxy-4-butylsulfonate] (PTEBS) using the Layer-by-Layer technique. The electromagnetic radiation used to excite the PTEBS induces a local electromagnetic field on the surface of the bimetallic cores that enhances the excitation and emission rates of the PTEBS, yielding a metal enhanced fluorescence (MEF). This effect was studied as a function of the bimetallic core size and the separation distance between the PTEBS and the bimetallic cores. Our results permit evaluation of the effect that the metallic core size of colloidal particles exerts on the MEF for the first time, and prove the relevance of the metallic cores to extend the effect far away from the metallic surface.

Immobilization of antimicrobial peptide IG-25 onto fluoropolymers via fluorous interactions and click chemistry.

We report a practical method for biofunctionalization of fluoropolymers based on noncovalent, fluorous interactions and click chemistry that allows incorporation of biomolecules under physiological solutions. We demonstrate the method by immobilization of an antimicrobial peptide (AMP) on fluorous thin films and fluorosilicone contact lens. The fluorous surfaces were dip-coated with fluorous-tagged oligo(ethylene) chain terminated with a reactive group, such as an alkynyl group. This simple step generates a "clickable" surface. The noncovalent fluorous interaction was strong enough to allow subsequent covalent attachment of IG-25, a truncated version of the most extensively studied human AMP LL-37. The attachment was through copper-catalyzed click reaction between the alkynyl group on the surface and the azido-OEG tag at the N-terminus of IG-25. In comparison to surfaces presenting IG-25 randomly bound via carbodiimide chemistry, the surfaces presenting IG-25 tethering to the surface at the N-terminus via click chemistry displayed higher antibacterial activities against an ocular pathogen Pseudomonas aeruginosa (strain PA-O1).

Synthesis of thermosensitive microgels with a tunable magnetic core.

In this work, we describe a new methodology for the preparation of monodisperse and thermosensitive microgels with magnetic core. In order to produce such a material, hydrophobic magnetic Fe(3)O(4) nanoparticles were prepared by two methods: thermal decomposition and coprecipitation. The surface of these nanoparticles was modified by addition of 3-butenoic acid, and after that these nanoparticles were dispersed in water and submitted to free radical polymerization at 70 °C in the presence of N-isopropylacrylamide (NIPAM) and bisacrylamide. The result of this reaction was monodisperse microgels with a magnetic core. By varying the amount of 3-butenoic acid, it was possible to obtain hybrid microgels with different magnetic core sizes and different architectures.