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A novel degradable microgel based on poly(N-isopropylacrylamide) (pNIPA) cross-linked with N,N’-bisacryloylcystine (BISS) and containing superparamagnetic iron oxide nanoparticles (SPION@CA) was synthesized by semi-batch precipitation polymerization and examined as a potential hyperthermia-enhanced drug carrier. The pNIPA provided the microgel with temperature sensitivity, the BISS was responsible for degradation in the presence of glutathione (GSH) (an –S–S–bond reductor naturally present in cells), while the SPION@CA permitted remote control of temperature to improve drug release. The microgels exhibited volume phase transition temperature at ca. 34 °C, which is near the human body temperature, and were stable across a wide range of temperatures and ionic strengths, as well as in the blood plasma at 37 °C. It was found that the presence of SPION@CA in the polymer network of the microgels enabled the temperature to be increased up to 42 °C by an alternating magnetic field, and that increasing the temperature from 37 to 42 °C significantly enhanced the releasing of the anticancer drug doxorubicin (DOX). The highest DOX release (82%) was observed at pH 5, 42 °C, and in the presence of GSH, and the lowest (20%) at pH 7.4, 37 °C, and in the absence of GSH. MTT assay indicated that compared to free doxorubicin, the microgel particles loaded with doxorubicin have comparable cytotoxicity against MCF-7 cancer cells while being significantly less toxic to MCF-10A healthy cells. Graphical abstract

We successfully synthesized a novel hydrogel based on derivatives of natural α-amino acids: ornithine and cystine. To make ornithine attachable to the polymer chain, the δ-amino group was modified with an acryloyl group and the main monomer was obtained. From cystine, the cross-linker

Combining hydrogels sensitive to external stimuli with conducting surfaces opens new possibilities in electrochemistry. Thin hydrogel layers as unique electrode-modifying materials provide highly permeable matrix for easy diffusion of analytes. In addition, larger individuals, for example, nanoparticles and enzymes, can be straightforwardly immobilized in the polymeric networks at electrode surfaces. Such properties are strongly desired for construction of sensors and biosensors. In addition, sensitivity to external stimuli allows to significantly enhance or weaken the electroanalytical signal. Recently, a significant number of articles concerning switchable sensors/biosensors, switchable electrochemical systems and signal–responsive interfaces have been published. This report is also focused on the construction of various devices based on electrode surfaces modified with smart hydrogel layers, for example, logic gates and electroresponsive hydrogel layers as potentially advanced drug delivery systems, artificial muscles and electrochemical valves.

We synthesized ion pair receptors 1 and 2 consisting of a benzocrown ether cation binding site and a ferrocene-supported squaramide anion binding domain and compared their binding ability with anion receptor 3, lacking a crown ether unit, using spectroscopic, spectrophotometric, and electrochemical measurements in acetonitrile solution. All receptors were obtained in a modular fashion by sequential amidation of dimethyl squarate with corresponding amines, which allows for the simple introduction of a ferrocene unit and enables them to act as sensors. We found that ion pair receptors 1 and 2 recognized the tested anions more strongly in the presence of cations, whereas the homotopic anion receptor 3 was unable to bind sodium or potassium salts more strongly than tetrabutylammonium salts. This enhancement in anion binding was attributed to a cation complexation induced alteration in the nature of the phenyl ring substituents, directly linked to the squaramide anion binding site, changing from electron-donating to more withdrawing. Solid state X-ray measurements support this design principle of the receptors and reveal strong coordination of anions and cations to the corresponding binding domains. In both 1·NaCl and 2·KCl systems, organic moieties linked by the cations form 1-D polymeric structures in the crystal lattice. However, in the case of the 2·NaCl complex the polymers’ shape and orientation result in the formation of porous crystals with approximately 12% of the space unoccupied. Electrochemical measurements showed when the ion pair receptors (but not the anion receptor) were pretreated with sodium or potassium cations, the addition of anions resulted in greater changes in oxidation and reduction potentials compared to the addition of anions to the same receptors in the absence of cations. Overall, the study demonstrates that squaramides offer a convenient platform for constructing ion pair sensors in modular fashion by varying the cation binding site and reporters. This opens up the possibility of recognizing salts in real life scenarios where simultaneous binding of anions and cations is needed.

In contrast to monotopic receptor 3, the anthracene functionalized squaramide dual-host receptor 1 is capable of selectively extracting sulfate salts, as was evidenced unambiguously by DOSY, mass spectrometry, fluorescent and ion chromatography measurements. The receptors were investigated in terms of anion and ion pair binding using the UV–vis and 1H NMR titrations method in acetonitrile. The reference anion receptor 3, lacking a crown ether unit, was found to lose the enhancement in anion binding induced by the presence of cations. Besides the ability to bind anions in an enhanced manner exhibited by ion pair receptors 2 and 4, changing the 1-aminoanthracene substituent resulted in their exhibiting a lower anion affinity than receptor 1. By using receptor 1 and adjusting the water content in organic phase it was possible to selectively detect sulfates both by “turn-off” and “turn-on” fluorescence, and to do so homogenously and under interfacial conditions. Such properties of receptor 1 have allowed the development of a new type of sensor capable of recognizing and extracting potassium sulfate from the aqueous medium across a phase boundary, resulting in an appropriate fluorescent response in the organic solution.

Nanogels are promising carriers for drug delivery, especially when they degrade under conditions typical for cancer cells to release a drug. By using the precipitation polymerization we synthesized a biocompatible and degradable nanogel based on poly(ethylene glycol) methyl ether methacrylate (OEGMA) and di(ethylene glycol) methyl ether methacrylate (MEO2MA) cross-linked with a redox-sensitive linker, N,N′-bis(methacryloyl)cystine – (mBISS). The application of appropriate proportions of monomers during the nanogel synthesis allowed us to set its volume-phase-transition temperature to the body temperature while the aggregation of the nanogel in physiological conditions was eliminated. The presence of carboxylic groups in mBISS made the nanogel sensitive to pH, gave it stability under conditions of high ionic strength and allowed it to bind the anticancer drug – doxorubicin (DOX). The degradation of nanogel was examined by using electron microscopies. In the presence of a high concentration of glutathione (a reducing agent for the -S-S- bridges) which is the case for most cancer cells, the spherical shape of the nanogel and correspondingly its structure were destroyed. The obtained profiles for the release of DOX from the nanogel revealed that the smallest amount of DOX was released from the nanogel at pH 7.4, while under conditions present in most cancer cells, this is at pH 5.0 and cGSH = 40 mM, the highest cumulative release of DOX was observed. The DOX loaded nanogels were cytotoxic against MCF-27 and HT-29 cancer cells similarly to DOX alone. The unloaded gel nanoparticles did not inhibit proliferation of the cells.

Negatively charged, pH-sensitive, very thin gel layers with accumulated hexaammineruthenium (II)/(III) were deposited on conducting surfaces. The gel was synthesized by applying an electrochemically induced free-radical polymerization method. This method allowed covering the electrode surface with an uniform and compact layer. The modified electrodes exhibited excellent current switch on/off behavior in response to changes in pH. However, the main goal of this study was to achieve the control of the layer thickness by changing the oxidation state of hexaammineruthenium. The layers could be reversibly swollen/shrinked by applying appropriate potentials.

The formation of a supramolecular core–shell like assembly upon interaction of the receptor with potassium sulfate enables its selective extraction., Selective extraction of sulfates in the form of alkali metal salts using charge-neutral molecular receptors is one of the holy grails of supramolecular chemistry. Herein we describe, for the first time, a squaramide-based ion pair receptor equipped with a crown ether site that is able to extract potassium sulfate from the aqueous to the organic phase (an analogous monotopic anion receptor lacking the crown ether unit lacks this ability). 1H NMR, UV-vis, DOSY-NMR, DLS, and MS experiments and the solid-state single crystal structure provided evidence of the formation of a supramolecular core–shell like assembly upon interaction of the receptor with potassium sulfate. The presence of monovalent potassium salts, in contrast, promoted the formation of simple 1 : 1 complexes. Unlike the 4 : 1 assembly, the 1 : 1 complexes are poorly soluble in organic media. This feature was utilized to overcome the Hofmeister bias and allow for selective extraction of extremely hydrophilic sulfates over lipophilic nitrate anions, which was unambiguously proved by quantitative AES and ion chromatography measurements. A simple modification of the receptor structure led to a “naked eye” optical sensor able to selectively detect sulfates under both SLE and LLE conditions.

We have successfully synthesized a novel microgel the volume of which could be reversibly changed by using an electrochemical trigger. At appropriate potential and at human-body temperature the volume change was unusually high – by more than one order of magnitude. The starting material was a thermoresponsive microgel built from N-isopropylacrylamide, sodium acrylate and N,N′-bisacryloylcystine as the crosslinker. The gel has been modified with aminoferrocene through amid-bond formation. The influence of oxidation state of the ferrocene groups in the microgel on volume phase transition temperature was determined. The –S–S– groups from the N,N′-bisacryloylcystine linker were employed in the chemisorption of the microgel particles on the Au electrode surface and the formation of gel monolayers. It appeared that the microgel layers could be either in the shrunken- or the swollen state depending on the oxidation number of the iron atoms in the ferrocene groups. The oxidation number could be changed electrochemically and the shrunken–swollen transformation could be repeated many times. The properties of the obtained materials were examined with dynamic light scattering technique, UV–vis spectroscopy, SEM and TEM microscopies and cyclic voltammetry.

Positively-charged very thin gel layers were deposited on conducting surfaces by an electrochemically-induced free-radical polymerization method. This method allowed the formation of a uniform and compact layer. 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, an electroactive compound with two sulphonate groups that form a dianion in aqueous solutions (ABTS2-), was introduced into the layer to act as an additional cross-linker. The gel layer could be reversibly swelled and shrunk by electrooxidizing/electroreducing the ABTS2- linker.

The use of a squaramide-based ion pair receptor offers a solution to the very challenging problem of extraction and transport of extremely hydrated sulfate salt. Herein we demonstrate for the first time that a neutral receptor is able not only to selectively extract but also to transport sulfates in the form of an alkali metal salt across membranes and to do so in a cooperative manner while overcoming the Hofmeister bias. This was made possible by an enhancement in anion binding promoted by cation assistance and by diversifying the stoichiometry of receptor complexes with sulfates and other ions. The existence of a peculiar 4:1 complex of receptor 2 with sulfates in solution was confirmed by UV–vis and 1H NMR titration experiments, DOSY and DLS measurements, and supported by solid-state X-ray measurements. By varying the separation technique and experimental conditions, it was possible to switch the depletion of the aqueous layer into extremely hydrophilic or less lipophilic salts, thus obtaining the desired selectivity., Formation of a supramolecular core−shell-like assembly upon interaction of the receptor with potassium sulfate enables its transport across membrane.

Environmentally sensitive, degradable microgels based on poly(N-isopropylacrylamide) (pNIPA) cross-linked with the diacryloyl derivative of cystine (BISS) were synthesized by applying surfactant-free emulsion polymerization. pNIPA contributed the sensitivity to temperature to the microgels and the cross-linker made them degradable and sensitive to pH. The morphology of the microgels was investigated by using scanning and transmission electron microscopies (SEM and TEM). The gels formed spherical particles with a narrow size distribution. The influence of temperature, pH and ionic strength on the swelling behavior and the stability of new microgels with various contents of BISS (0, 1 and 3%) were investigated by dynamic light scattering (DLS). It was found that microgels with 3% content of amino acid were highly stable over a wide range of investigated temperatures, pH values and ionic strengths, including the physiological conditions (pH = 7.4, IS = 0.15 M, and 37 °C). The reduction-induced degradation of these microgels by 0.01 M solution of dithiothreitol (DTT) or glutathione (GSH) was studied by means of SEM and TEM; the obtained micrographs showed the destruction of spherical microgel particles. The microgels containing 3% of BISS could be loaded with doxorubicin (DOX) by employing the electrostatic interactions between the DOX amine group and the ionized carboxyl group from BISS. A significant increase in the cumulative release of DOX was observed after changing pH from that characteristic to blood (∼7.4) to that existing in affected cells (∼5.0) and in the presence of GSH (CGSH ∼ 10 mM). The cytotoxicity tests proved that the obtained microgels are interesting as useful carriers in directed drug delivery systems.

A conducting microcomposite composed of cross-linked poly(N-isopropylacrylamide) (pNIPA) and polyaniline (PANI) was synthesized. First, pNIPA gel microcapsules were prepared via surfactant-free emulsion polymerization (SFEP). Then by soaking the gel with a solution of an oxidizing agent (sodium persulfate) and placing it in a solution of aniline in nitrobenzene the conducting polymer was formed in pNIPA. The structure, morphology, swelling behavior and polyaniline oxidation state in the composite were investigated using SEM, TEM, DLS and Raman spectroscopy. The new microcomposite consists of micro-spheres, undergoes rapid volume phase transition and is electroactive. A result of the transition from the swollen to the collapsed state is a strong enhancement of the voltammetric peaks of polyaniline.

Regularly sized platinum electrodes were modified with a layer of thermosensitive hydrogel based on poly(N-isopropylacrylamide) and containing different amounts of crosslinker. The layers were formed by using the electrochemically induced free radical polymerization. The transport of electroactive species through the layers was examined in function of crosslinker content and for two possible forms of the hydrogel. It was found that in the shrunken state, within a specific scan-range, the shape of the voltammograms was typical for a set of independent micro/nanoelectrodes, while in the swollen state of the layers the voltammograms were peak-shaped in the entire scan-rate range. This was a result of either through-film transport (swollen layer) or pinhole/pore (shrunken layer) diffusion of electroactive species. 2% content of crosslinker caused the biggest limitation to the probe transport to the electrode surface.

A hydrogel based on poly(N-isopropylacrylamide) (NIPA) crosslinked with the diacryloyl derivative of cystine (BISS) was synthesized using the free radical polymerization. The NIPA-BISS hydrogel rich in cystine appeared to be a competitive sorbent and has been applied to efficiently remove heavy metal pollutants, mainly cadmium and lead ions, from water. Sorption capacity, kinetics of sorption, swelling behavior and effect of pH on sorption were investigated. Scanning electron microscopy and FTIR analysis were employed to monitor the changes that took place in the NIPA-BISS hydrogels after the adsorption of Cd(II) and Pb(II).

A new method of modification of the gold-electrode surface with a microgel monolayer was developed. Microgel particles contained –S-S– groups to enable modification of the gold surface by self-assembly via the chemisorption process. The particles were obtained by precipitation polymerization of N-isopropylacrylamide with N,N′-bis(acryloyl)cystine cross-linker. Their spherical shape and highly uniform dispersion were confirmed by electron microscopies (SEM and TEM). Thermosensitivity of the microgel was investigated with dynamic light scattering (DLS). The formation of monolayers was monitored with a quartz-crystal microbalance. The morphology of the modified surface in its dry state and in aqueous environment was investigated with atomic force microscopy (AFM). At temperatures below the volume-phase-transition temperature the microgels formed a densely packed structure that well covered the entire surface. A significant change in morphology was observed after raising temperature above the volume-phase-transition temperature. The observed increase in roughness of the modified surface suggested that the surface of electrode could be locally, between the microgel particles, uncovered. The electrochemical properties of the modified electrode were investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). A strong influence of the volume phase transition in the microgels attached to the Au surface on CV and EIS responses of the modified electrode was found. The observed behavior was reversed to that of the electrodes modified with a thin thermosensitive gel film based on N-isopropylacrylamide, i.e. the volume phase transition led to a significant increase in the voltammetric current and to a drop in electron transfer resistance. That was related to partial uncovering of the electrode surface after the shrinking process in the microgels.

Composites containing conductive polymers and Au and Ag nanoparticles were introduced into the environmentally sensitive poly(N-isopropylacrylamide) hydrogel channels. The composites were synthesized directly in the channels by two phase polymerization procedure. In the first step the unmodified hydrogel was placed in a solution containing the oxidizing agent (HAuCl4 or AgNO3), and in the second step it was placed in a solution of aniline in nitrobenzene. The presence of polyaniline and metal nanoparticles increased conductivity of both types (ionic and electron) while the hydrogel properties, such as: flexibility, plasticity and ability to phase transition, were preserved. The presence of nobel-metal nanostructures added catalytical activity to the new materials. Optical and SEM investigations revealed that polymer-metal composites were uniformly distributed in the entire gel samples. NIPA-PANI-Au composites exhibited a sharp volume phase transition in response to changes in temperature and ionic strength. That behavior was similar to unmodified poly (N-isopropylacrylamide) hydrogel. The new material was electroactive and had electrocatalytical properties towards electrooxidation of ethanol. Electroactivity of the modified gel was a strong function of the swelling ratio; the shrinking process enhanced the voltammetric response.

Synthesis of environmentally-sensitive, and therefore smart hydrogels of micro- and nanosize allowed substantial shortening of time of response of these gels to a change in environmental conditions. This made the hydrogels much more attractive and opened new possibilities of their applications. In this paper we present recent developments in ways of construction of micro- and nanogels, their adaptation to particular needs and possibilities of use. The focus was given to individual, spherical particles and very thin layers of gels on solid supports, including electrodes.

Thin hydrogel layers, based on a negatively charged cross-linked polymeric network, were deposited on conducting surfaces by means of an electrochemically induced free-radical polymerization method. The presence of ionized carboxylic groups in the polymer network allowed for the effective accumulation of Cu(II) cations in the hydrogel layer; these Cu(II) cations acted as an additional electroactive cross-linker and caused a substantial shrinking of the layer. It was found that the Cu(II) complexed by the polymer network could be electrochemically reduced to Cu(I) and that led to substantial swelling of the layer. Subsequent electrooxidation of Cu(I) led to the reformation of the crosslinking complexes, and again the shrinking of the layer was observed. The electrochemically active hydrogel layer deposited on the electrode surface was able to act as a microactuator due to its fast action, high stability, and reversibility of the shrinking/swelling transformation. The changes in hydrogel layer thickness were monitored by an electrochemical quartz crystal microbalance and confirmed by electron microscopy.

The influence of the presence of positively charged gel layers deposited on the electrode surface on reduction and oxidation of ionic substances in the absence of deliberately added supporting electrolyte was examined. The gel layers based on crosslinked copolymer of N-isopropylacrylamide (NIPA) and N-(3-aminopropyl)methacrylamide hydrochloride were used. The polymer net was positively charged in a wide pH range. Differently charged ferrocene derivatives, ferrocenyltrimethylammonium cation (FcN+), sodium salt of ferrocenylmethyl-3-mercapto-1-propanesulfonic acid (FcS−) and 1,1’-ferrocenedimethanol (Fc(MeOH)2), were used as the electroactive probes. It appeared that the depression of the oxidation current of cations was much stronger compared to bare electrodes; the depression factor equaled circa 2. The increase in oxidation current of anions was also strongly enhanced compared to bare electrodes; it amounted to 1.7 times. Addition of excess supporting electrolyte to the solution led to cancelling of major current changes. It meant that sufficiently concentrated supporting electrolyte eliminated not only regular migrational contribution but also strongly influenced the electrostatic-interactions between charged probes and charged polymer network.

In this paper we report on synthesis of pH sensitive and degradable microgel for a high-capacity doxorubicin-drug carrier. Microgel was based on poly(acrylic acid) cross-linked with a redox-sensitive linker - N,N’-bis(acryloyl)cystamine, and was synthesized by using the distillation polymerization. Highly monodispersed spherical particles were obtained. The presence of carboxylic groups in the chains gave pH-sensitivity to the microgel; as a result the microgel size changed after a change in pH. The presence of disulfide bridges in the microgels gave them the ability to degrade. The extent of degradation of the microgel was examined by using the dynamic light scattering technique and electron microscopy. The degradation of the microgel was caused by the reduction of -S-S- bridges by glutathione. At the beginning of the degradation process the swelling of the microgel particles was observed because only a part of disulfide bonds were broken. The break of the remaining -S-S- bonds led to the complete degradation of the microgel. The fact that the microgel consisted mainly of the carboxylic groups allowed us to bind a high amount of the anticancer drug. Under the conditions typical for cancer cells, i.e. at pH 5 and in the presence of increased concentration of glutathione, the highest amount of doxorubicin could be released. The MTT assay indicated that compared to free doxorubicin the microgel particles loaded with doxorubicin were more cytotoxic against the MCF-7 breast cancer cells, while they were 27 times less toxic against the MCF-10A healthy cells.

We present a novel microgel with the capacity for self-assembly, the volume of which can be altered by performing the appropriate redox reaction. The initial thermoresponsive microgel was synthesized from N-isopropylacrylamide and N-(3-aminopropyl)methacrylamide, with N,N′-bisacryloylcystine used as the crosslinker. The obtained microgel polymer network was modified with benzoquinone through the Aza-Michael addition reaction. The influence of the redox state of the benzoquinone groups in the microgel on volume phase transition temperature was examined. The disulfide bridges from the N,N′-bisacryloylcystine linker were used to attach microgel particles on an Au electrode surface, forming a monolayer. The monolayer formation and the volume phase transition within the microgel were monitored with the QCM technique. The redox state of the electroactive benzoquinone groups in the polymer network appeared to be the key factor determining whether the microgel layers exist in the shrunken or swollen state. The oxidation state can be changed electrochemically and the shrinking-swelling transformation was shown to be reversible. The obtained material was also studied with dynamic light scattering technique and electron microscopies.

Using a combination of two LCST-type polymers a set of new core-shell microgels was obtained. Interestingly, the swelling behavior of obtained core-shell microgels was characteristic for the polymeric gels that possess both UCST-type and LCST-type properties. The cores were based on cross-linked poly(N-isopropylacrylamide-sodium acrylate) and were obtained by employing the precipitation polymerization. Then, the shells, based on cross-linked poly(N-isopropylacrylamide-sodium acrylate), were built over the cores via the seed polymerization. The swelling behaviors of the microgels were investigated by doing DLS experiments in a temperature range of 20–50 °C. This microgel appeared to be the first relatively simple system that can exist in the swollen state only in a narrow temperature range. The swelling of the microgels took place at temperature below the volume phase transition temperature (VPTT). The maximum value of radius appeared at VPTT of the core. This phenomenon was observed for various compositions of the core and the shell and in a wide range of pH. Differential scanning calorimetry measurements showed that the swelling process occurring at a temperature below VPTT is endothermic. The reported particle properties may open new possibilities in application of such materials in the fields of controlled release of various molecules, construction of sensors and chemical separations.

Transport of a redox probe to the surface of an electrode modified with a pH-sensitive polymer network was investigated. After becoming appropriately charged the hydrogel film could act as an electrostatic barrier for negatively charged probes. In the example studied, the charge was obtained by dissociating the carboxylic groups in the polymer network. The percentage of dissociation was determined by the pH of the solution. In parallel, the contribution of migration also played an important role in the transport of the probes. Both regular-sized electrodes and microelectrodes were used in the electrochemical experiments. Keywords: Hydrogel layers, Microelectrode modification, Diffusional and migrational transport

Thermoresponsive pNIPA (poly (N-isopropylacrylamide)) gels modified with dopamine methacrylamide were synthesized using free-radical polymerization. In this way, the catechol groups were introduced into the polymer network. The presence of dopamine in the gel led to a significant shift in the volume phase transition temperature (VPTT). It was found that hydrogels were electroactive and that oxidation of catechol groups also led to a strong shift in the VPTT. The temperature window, that is, the range of temperature where volume of the gel could be substantially changed by oxidation of the catechol groups, for the gel formed from the polymerization solution containing 5% of the dopamine derivative, was 30–40 °C. Additionally, the influence of Fe3+ ions, which form the most stable complexes with dopamine, on swelling behavior of the gels was investigated at various pH. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017

Substantially improved hydrogel particles based on poly(N-isopropylacrylamide) (pNIPA) have been obtained. First, as a result of replacing commercially available N,N'-bis(acryloyl)cystamine (BAC), the crosslinker, with acryloyl derivative of cystine containing a carboxylic group (BISS), the hydrogel particles acquired improved stability vs. ionic strength and allowed further chemical modification of the chains, including the attachment of drug molecules. Next, a redox-initiated aqueous precipitation polymerization via the semi-batch method was used. This led to substantially increased BISS content and diminished size of the nanoparticles that made them suitable to an endocytic process. In addition, the obtained nanogels revealed high loading capacity of anticancer drug vs. dry gel (circa 16%) and they exhibited much better stability and enhanced drug release under the typical conditions existing in cancer cells. Size of obtained nanogels was investigated by dynamic light scattering (DLS). It appeared that nanoparticle size was in the range from ca. 40 to 200nm. In 0.01M solution of glutathione (GSH) the -S-S- bonds were reduced and the nanogel particles were degraded. This could be seen in obtained SEM and TEM micrographs. The cytotoxicity investigation against the HeLa cells showed that DOX loaded nanogels were more cytotoxic (IC50=0.51μM) than free DOX (IC50=0.83μM), while unloaded nanogels did not inhibit proliferation of the cells. It was also found that the nanogels loaded with DOX reached a high intracellular concentration in HeLa cells just after 2h while free DOX needed 6h for that.

Polymer microcapsules offer a possibility of storing increased amounts of drugs. Appropriate design and composition of the microcapsules allow tuning of the drug-release process. In this paper, we report on synthesis of hydrogel microcapsules sensitive to temperature and pH and degradable by glutathione and hydrogen peroxide. Microcapsules were based on thermo-responsive poly(N-isopropylacrylamide) and degradable cystine crosslinker, and were synthesized by applying precipitation polymerization. Such way of polymerization was appropriately modified to limit the crosslinking in the microcapsule center. This led to a possibility of washing out the pNIPA core at room temperature and the formation of a capsule. Microcapsules revealed rather high drug-loading capacity of ca. 17%. The degradation of the microcapsules by the reducing agent (GSH) and the oxidizing agent (H2O2) was confirmed by using the DLS, UV-Vis, SEM and TEM techniques. Depending on pH and concentration of the reducing/oxidizing agents a fast or slow degradation of the microcapsules and a burst or long-term release of doxorubicin (DOX) were observed. The DOX loaded microcapsules appeared to be cytotoxic against A2780 cancer cells similarly to DOX alone, while unloaded microcapsules did not inhibit proliferation of the cells.