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A feature article is presented on recent developments in the investigation of stimuli responsive polymers and their biomedical applications. Polymer systems are grouped with respect to sensitivity to changes in temperature, pH, light, redox potential and other special changes in environment. Underlying principles and possible applications of various systems are discussed. Critical evaluation of all benefits but also drawbacks of a particular stimuli responsivity is therefore necessary when planning the construction of multi-stimuli responsive systems. Special focus is devoted to biological consequences of physico-chemical properties of the polymer materials. [ABSTRACT FROM AUTHOR]

Abstract: Acridines are potent DNA-intercalating anticancer agents with high in vivo anticancer effectiveness, but also severe side effects. We synthesized five 9-anilinoacridine-type drugs and their conjugates with biocompatible water-soluble hydrazide polymer carrier. All of the synthesized acridine drugs retained their in vitro antiproliferative properties. Their polymer conjugates were sufficiently stable at pH 7.4 (model of pH in blood plasma) while releasing free drugs at pH 5.0 (model of pH in endosomes). After internalization of the conjugates, the free drugs were released and are visible in cell nuclei by fluorescence microscopy. Their intercalation ability was proven using a competitive ethidium bromide displacement assay. [Copyright &y& Elsevier]

Abstract: Drug delivery systems based on thermoresponsive polymers might serve as suitable carriers for local radiotherapy. We have, therefore, designed and synthesized a radioiodine-labellable thermoresponsive polymer. The polymer was synthesized by copolymerization of N-isopropylacrylamide with N-methacryloyl tyrosinamide in tetrahydrofuran, and then labelled by 131I. The solution of this labelled polymer in dimethylsulfoxide (4.4MBq/ml; 1.8wt% polymer) was applied to femoral muscle of male Balb/C mice (50μl per animal). The biodistribution and excretion of radioactivity was followed in 2h and 1, 7, 14, 28 and 42d post injection (n=6 per time point). As expected, the labelled polymer was left on the application site (ca 90% 2h post injection), decreasing slowly to ca 80% within 14d. At 28d post injection, ca 70% of the injected activity was still found on the application site, decreasing to ca 60% at 42d. No organ-specific accumulation of the radioactivity released from the application site, including thyroid, was observed. Majority of the released radioactivity was excreted via urine and faeces. This preliminary study suggests that thermoresponsive polymers could be used as an effective delivery system for localized radiotherapy. [Copyright &y& Elsevier]

Abstract: The alpha emitter 211At is a prospective radionuclide for the therapy of smaller tumours and metastases. However, the chemical properties of 211At together with the fact that it is available only in trace amounts, makes the labelling of prospective astatine carriers rather complicated. In this context we have studied a new class of possible astatine carriers—nanoparticle systems, which tend to concentrate themselves in some types of tumours by means of the EPR effect. Additionally, such nanoparticles have the advantage that they may be chemically modified by the attachment of a tumour-seeking agent, and also directly applied to the target site. In order to reach high labelling yields, and in order to protect the nanoparticles from rapid degradation by the immune system, silver-containing particles covalently coated by poly(ethylene oxide) were developed and tested. The effect of the different reducing and oxidizing agents on the labelling yield was also determined. It was found that labelling yields were almost quantitative and well reproducible under reducing conditions, while under oxidizing conditions they dropped to ca. 50%. In the absence of any reducing or oxidizing agent, the labelling yields were randomly distributed between a range of 50% and 97%. The labelled nanoparticles were stable even in a large surplus of competing chloride ions. [Copyright &y& Elsevier]

Abstract: Stationary phase containing quinolin-8-ol immobilized on macroporous methacrylate support for the affinity chromatography of porcine pepsin A is described. Optimized chromatographic conditions for separation of porcine pepsin A on this stationary phase were found investigating the influence of pH, concentration, ionic strength and chemical composition of the used mobile phases. The stationary phase shows a good reproducibility of chromatographic analyses (relative standard deviation, ±2%), a high recovery (ca. 93%) and a satisfactory capacity (13mg pepsin A/1mL stationary phase) for porcine pepsin A. The obtained findings confirm the applicability of affinity chromatography on the stationary phase with immobilized quinolin-8-ol to the isolation and determination of porcine pepsin A. [Copyright &y& Elsevier]

Abstract: A novel polymeric micellar pH-sensitive system for delivery of doxorubicin (DOX) is described. Polymeric micelles were prepared by self-assembly of amphiphilic diblock copolymers in aqueous solutions. The copolymers consist of a biocompatible hydrophilic poly(ethylene oxide) (PEO) block and a hydrophobic block containing covalently bound anthracycline antibiotic DOX. The starting block copolymers poly(ethylene oxide)-block-poly(allyl glycidyl ether) (PEO-PAGE) with a very narrow molecular weight distribution (M w/M n ca. 1.05) were prepared by anionic ring opening polymerization using sodium salt of poly(ethylene oxide) monomethyl ether as macroinitiator and allyl glycidyl ether as functional monomer. The copolymers were covalently modified via reactive double bonds by the addition of methyl sulfanylacetate. The resulting ester subsequently reacted with hydrazine hydrate yielding polymer hydrazide. The hydrazide was coupled with DOX yielding pH-sensitive hydrazone bonds between the drug and carrier. The resulting conjugate containing ca. 3 wt.% DOX forms micelles with R h a=104 nm in phosphate-buffered saline. After incubation in buffers at 37 °C DOX was released faster at pH 5.0 (close to pH in endosomes; 43% DOX released within 24 h) than at pH 7.4 (pH of blood plasma; 16% DOX released within 24 h). Cleavage of hydrazone bonds between DOX and carrier continues even after plateau in the DOX release from micelles incubated in aqueous solutions is reached. [Copyright &y& Elsevier]

Sorbents containing quinolin-8-ol groups were synthesized by the chemical transformation of macroporous poly(glycidyl methacrylate-co-ethylene dimethacrylate) copolymer using the Mannich reaction. These sorbents were transformed into Ag(I), Cu(II), and Fe(III) forms, respectively. The interactions with substituted phenols were studied by inverse liquid chromatography. Phenols are retained more strongly on the metal complexes of quinolin-8-ol sorbent than on the uncomplexed quinolin-8-ol sorbent. Strong interactions of benzene-1,2-diols, benzene-1,2,3-triols and 4-nitrophenol with the adsorbent in the Cu(II) and Fe(III) form are explained by the chelate effect or by ionic bond formation. The intensity of the interactions decreases when the eluents are exchanged from water or water/methanol mixtures to the less polar methanol. [Copyright &y& Elsevier]

The biological effects of titanium (Ti) in the form of Ti(IV)-ascorbate on oats (Avena sativa L. cv. Zlata`k) were studied in hydroponic experiments on defined nutrient solutions, determining the influence (i) of the chemical form of nitrogen (N) in nutrient solution on the Ti effects on plants (nitrate and an ammonium salt (acetate) were the only N species used) and (ii) of various Ti concentrations in nutrient solution while changing the magnesium (Mg) concentration on the Ti, Mg, iron (Fe), and potassium (K) content in tops and roots, top and root dry weights, chlorophyll a and b content, top height, and root length. It was found that (i) Ti was beneficial for plants grown on the nitrate-containing nutrient solutions as compared to the ammonium-containing nutrient solutions where Ti results in inhibitory effects on plant health status (decrease of top and root dry weights, chlorophyll a and b contents, top height, and root length), therefore, it was deducted that the increase of nitrate reductase activity was mainly responsible for the Ti beneficial effect on plants and (ii) Ti increased the Fe, Mg, and Ti content in plant tissues and this effect was independent of N form in the nutrient solution, chlorophyll a and b content or plant health status. It is suggested that the biological effects of Ti (the synthesis of the Ti chelating α -hydroxy carboxylic acids (citric and malic), and ascorbic acid, the increase of the Fe and Mg contents in plant tissues, the increased nitrate reductase activity, the increased chlorophyll a and b biosynthesis, and the effects on the other enzymatic activities) are the defense mechanisms of the plant against Ti replacing some essential elements from their binding sites (probably mainly from the phosphate-based ones). These defense mechanisms are, in the case of the usual Ti application doses, much stronger than adequate for the elimination of the Ti toxic effects (this ‘‘paradox’’ effect... [ABSTRACT FROM AUTHOR]

Organophosphate neuroactive agents represent severe security threats in various scenarios, including military conflicts, terrorist activities and industrial accidents. Addressing these threats necessitates effective protective measures, with a focus on decontamination strategies. Adsorbents such as bentonite have been explored as a preliminary method for chemical warfare agent immobilization, albeit lacking chemical destruction capabilities. Chemical decontamination, on the other hand, involves converting these agents into non-toxic or less toxic forms. In this study, we investigated the hydrolytic activity of a Cu(II) complex, previously studied for phosphate ester hydrolysis, as a potential agent for chemical warfare decontamination. Specifically, we focused on a ligand featuring a thiophene anchor bound through an aliphatic spacer, which exhibited high hydrolytic activity in its Cu(II) complex form in our previous studies. Paraoxon, an efficient insecticide, was selected as a model substrate for hydrolytic studies due to its structural resemblance to specific chemical warfare agents and due to the presence of a chromogenic 4-nitrophenolate moiety. Our findings clearly show the hydrolytic activity of the studied Cu(II) complexes. Additionally, we demonstrate the immobilization of the studied complex onto a solid substrate of Amberlite XAD4 via copolymerization of its thiophene side group with dithiophene. The hydrolytic activity of the resultant material towards paraoxon was studied, indicating its potential utilization in organophosphate neuroactive agent decontamination under mild conditions and the key importance of surface adsorption of paraoxon on the polymer surface. [ABSTRACT FROM AUTHOR]

Main principles of applicability of polymers for biomedical purposes with the emphasis on their physico‐chemical properties and solution behavior are reviewed. The influence of molecular weight of the polymers and their degradability are also discussed. Thermosensitive polymers are pointed out including additional effects such as hydrogen bonds and vitrification. Several examples of polymers currently used or under development are presented and their advantages and drawbacks are analyzed. [ABSTRACT FROM AUTHOR]

Polymers are omnipresent materials that are widely used in medicine, e.g., as construction materials for medical devices or as polymer nanoparticle drug delivery systems. Therefore, their possible effects on biomolecules, such as lipids, proteins, and other molecules, present in the human body must be examined. This review addresses the effects of polymer materials (such as dendrimers, polysaccharides) on the process of amyloid fibril formation. Amyloidoses are very serious diseases that are characterized by amyloid deposition in various organs and tissues, causing their dysfunction. The treatment of amyloidoses, such as Alzheimer's disease (AD), using polymer materials is a challenge. Studies aiming to elucidate the effects of polymers on the process of amyloid fibril formation are therefore also of key importance for understanding the process of amyloid fibril formation and amyloidoses in general. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of joint replacement infection is a difficult clinical challenge that often occurs when the implant cannot be salvaged. We hypothesize that the pH value of synovial fluid could be an important indicator of the inflammatory status of the joint. However, in the literature, there is a lack of data on the pH changes in hip and knee joint replacements and their relation to infection and implant failure. In this study, we aimed to measure the pH levels of synovial fluid in patients with hip and knee joint replacements. We also investigated the potential of pH measurement as a diagnostic tool for joint replacement infection. In this study, we recorded the pH values to be 7.55 and 7.46 in patients where Pseudomonas aeruginosa was identified as the cause of the prosthetic joint infection. We attribute this to the different environments created by this specific bacterium. In other cases where the pH was higher, chronic mitigated infections were diagnosed, caused by strains of Staphylococcus aureus, Streptococcus agalactiase, and coagulase negative staphylococcus. Materials and methods: In our cohort of 155 patients with implanted hip (THA; n = 85) or knee (TKA; n = 70) joint replacements, we conducted a prospective study with a pH measurement. Out of the whole cohort, 44 patients had confirmed joint replacement infection (28.4%) (44/155). In 111 patients, infection was ruled out (71.6%) (111/155). Joint replacement infection was classified according to the criteria of the Musculoskeletal Infection Society (MSIS) from 2018. Based on the measured values, we determined the cut-off level for the probability of ongoing inflammation. We also determined the sensitivity and specificity of the measurement. Results: The group of patients with infection (n = 44) had a significantly lower synovial fluid pH (pH = 6.98 ± 0.48) than the group of patients with no infection (n = 111, pH = 7.82 ± 0.29, p < 0.001). The corresponding median pH values were 7.08 for the patients with infection and 7.83 for the patients with no infection. When we determined the cut-off level of pH 7.4, the sensitivity level of infected replacements was 88.6%, and the specificity level of the measurement was 95.5%. The predictive value of a positive test was 88.6%, and the predictive value of a negative test was 95.5%. Conclusions: Our results confirm that it is appropriate to include a pH measurement in the diagnostic spectrum of hip and knee replacements. This diagnostic approach has the potential to provide continuous in vivo feedback, facilitated by specialized biosensors. The advantage of this method is the future incorporation of a pH-detecting sensor into intelligent knee and hip replacements that will assess pH levels over time. By integrating these biosensors into intelligent implants, the early detection of joint replacement infections could be achieved, enhancing proactive intervention strategies. [ABSTRACT FROM AUTHOR]

The present article reports a simple and straightforward approach to access thermoresponsive graft copolymers based on lactide (LA) and a methacrylic monomer, 2‐hydroxypropyl methacrylate (HPMA), using a synthesized carboxy‐functionalized trithiocarbonate‐based chain transfer agent. One protocol involves a metal‐free simultaneous synthesis through a combination of reversible addition‐fragmentation chain transfer polymerization and organic acid‐catalyzed ring‐opening polymerization, which follows first‐order kinetics. The resulting copolymers with a controlled structure exhibit remarkably narrow molecular weight distributions (Ð < 1.10). Within this framework, the self‐assembly of PHPMA‐g‐PLA graft copolymers (GCs) into nanoparticles (NPs) is demonstrated at concentrations of 0.2 and 0.5 wt.%, respectively. The displacement method, based on the rapid injection of the organic solvent (acetone) into an aqueous medium under vigorous stirring, produces spherical NPs such as micelles, vesicles, or non‐spherical "lumpy rods". The presence of a pseudo‐thermoresponsive segment (PHPMA) in GCs facilitates stimulus‐responsive self‐assembly behavior. Well‐defined spherical NPs—primarily vesicles of substantial size—develop upon heating above the glass transition temperature (Tg ≈35–36 °C) of the GCs in an acetone–water (80/20 wt.%) mixture. Last, specific interactions between the obtained PHPMA‐g‐PLA nano‐objects and blood proteins in human plasma are studied using isothermal calorimetry. [ABSTRACT FROM AUTHOR]

Fluorescence correlation spectroscopy (FCS) provides most commonly values of diffusion coefficients of fluorescently labeled species in a solution, especially biopolymers. A newly developed procedure for the determination of diffusion coefficient distributions applicable to polydisperse polymers or nanoparticles, based on the well-known CONTIN algorithm, is described and tested on both simulated FCS correlation functions and real experimental data. Good resolution of bimodal distributions is observed, and it is quantitatively established how the resolution depends on the level of experimental noise. Effects of incorrect calibration of the focal volume on the obtained diffusion coefficient and its distribution are described for single-focus FCS. With rapid expansion of the FCS method from biology and biochemistry into the polymer field, and recently into many other disciplines including, e.g., environmental sciences, such a technique was very much needed. [ABSTRACT FROM AUTHOR]

[Display omitted] • One-pot ROP/RAFT synthesis of PLA- b -PDPA: Simplified process with controlled structure. • Droplet microfluidics enables precise fabrication of monodisperse microparticles. • pH-triggered transition from microparticles to vesicles for drug release and bacteria entrapment. Polymer particles with stimuli-responsive properties offer promising applications in healthcare, chemical reactors, development of artificial cells and organelles, as well as in the entrapment of bacteria. In this study, a novel biocompatible, biodegradable, and pH-responsive diblock copolymer based on polylactide (PLA) and poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) was synthesized via a metal-free one-pot/simultaneous ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) approach (ROP/RAFT). This copolymer was then employed to produce highly monodisperse microparticles using microfluidics droplet generation technique. Utilizing confocal microscopy imaging, a reversible pH-induced morphological transition from microparticles to vesicle-like structures was observed at pH 5.1. The reversible shift in morphology from microparticles to giant vesicles (Vs) in acidic environments is triggered by the protonation of amino groups of the PDPA block, rendering vesicle surfaces positively charged − an advantageous feature for attracting and engulfing negatively charged bacteria. Initial validation involved electrostatic interactions with negatively charged latex resin beads followed by assessing interaction capabilities with gram-negative bacteria, Escherichia coli (E. coli). Additionally, the reversible morphological transition of microparticles-to-vesicles was employed to study drug release at different pHs. This approach proven to be a promising strategy for targeted drug delivery and bacteria entrapment using smart pH-responsive microparticles. [ABSTRACT FROM AUTHOR]

Poly(lactic-co-glycolic acid) (PLGA) nanoparticle-based drug delivery systems are known to offer a plethora of potential therapeutic benefits. However, challenges related to large-scale manufacturing, such as the difficulty of reproducing complex formulations and high manufacturing costs, hinder their clinical and commercial development. In this context, a reliable manufacturing technique suitable for the scale-up production of nanoformulations without altering efficacy and safety profiles is highly needed. In this paper, we develop an inline sonication process and adapt it to the industrial scale production of immunomodulating PLGA nanovaccines developed using a batch sonication method at the laboratory scale. The investigated formulations contain three distinct synthetic peptides derived from the carcinogenic antigen New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) together with an invariant natural killer T-cell (iNKT) activator, threitolceramide-6 (IMM60). Process parameters were optimized to obtain polymeric nanovaccine formulations with a mean diameter of 150 ± 50 nm and a polydispersity index <0.2. Formulation characteristics, including encapsulation efficiencies, release profiles and in vitro functional and toxicological profiles, are assessed and statistically compared for each formulation. Overall, scale-up formulations obtained by inline sonication method could replicate the colloidal and functional properties of the nanovaccines developed using batch sonication at the laboratory scale. Both types of formulations induced specific T-cell and iNKT cell responses in vitro without any toxicity, highlighting the suitability of the inline sonication method for the continuous scale-up of nanomedicine formulations in terms of efficacy and safety. [ABSTRACT FROM AUTHOR]

Hydrazone conjugates of polymers with doxorubicin represent a very promising tool for cancer chemotherapy. However, these conjugates are very difficult to radiolabel with iodine radionuclides, which possess otherwise very advantageous nuclear properties to, e.g ., follow biodistribution. In this study, we developed a robust protocol for the high-yield radioiodination of hydrazone-type drug delivery systems with doxorubicin. In particular, it is crucial that the polymer radioiodination step be performed before the deprotection of the hydrazide and doxorubicin binding. [ABSTRACT FROM AUTHOR]

We synthesized statistical poly(2-isopropyl-2-oxazoline- co-2-butyl-2-oxazolines) (POXs) that are molecularly dissolved below their cloud point temperature in aqueous milieu and are incorporated into micellar nanoparticles of biocompatible Pluronic F127 (F127) after heating their solution above transition temperature, Ttr. A functional comonomer 2-(but-3-enyl)-2-oxazoline copolymerized into one of the POXs (polymer E) allows introduction of fenolic moieties and subsequent radionuclide labeling with iodine-125. Self-assembly of the polymer E with F127 leads to formation of radioactive nanoparticles with hydrodynamic diameter 20 nm in aqueous solution by heating to 37 °C. The nanoparticles are intended to be used as radioimaging tool in solid tumor diagnostics. [ABSTRACT FROM AUTHOR]

Abstract: We describe the synthesis of new crosslinker N′-{3-[2-(4-{2-[3-(methacryloylamino)propanoyl]hydrazono}cyclohexyliden)hydrazino]-3-oxopropyl}-2-methylacrylamide, which is stable at physiological pH, but is hydrolytically cleaved in acidic pH. Study of acid hydrolysis showed that the crosslinker is hydrolyzed into two N′-(3-hydrazino-3-oxopropyl)-2-methylacrylamide molecules and one 1,4-cyclohexanedione molecule. Hydrogels based on poly[N-(2-hydroxypropyl)methacrylamide] crosslinked with this crosslinker were prepared and their degradation rate was studied as a function of pH (in the range of pH 1.5–7.4). The hydrogel is cleaved within 8–27 days at pH between 1.5 and 6 and is stable at pH 7.4 making it promising for the construction of oesophageal stents. [Copyright &y& Elsevier]

As a natural polysaccharide polymer, glycogen possesses suitable properties for use as a nanoparticle carrier in cancer theranostics. Not only it is inherently biocompatible, it can also be easily chemically modified with various moieties. Synthetic glycogen conjugates can passively accumulate in tumours due to enhanced permeability of tumour vessels and limited lymphatic drainage (the EPR effect). For this study, we developed and examined a glycogen-based carrier containing a gadolinium chelate and near-infrared fluorescent dye. Our aim was to monitor biodistribution and accumulation in tumour-bearing rats using magnetic resonance and fluorescence imaging. Our data clearly show that these conjugates possess suitable imaging and tumour-targeting properties, and are safe under both in vitro and in vivo conditions. Additional modification of glycogen polymers with poly(2-alkyl-2-oxazolines) led to a reduction in the elimination rate and lower uptake in internal organs (lower whole-body background: 45% and 27% lower MRI signals of oxazoline-based conjugates in the liver and kidneys, respectively compared to the unmodified version). Our results highlight the potential of multimodal glycogen-based nanopolymers as a carrier for drug delivery systems in tumour diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Tuberculosis represents a major global health problem for which improved approaches are needed to shorten the course of treatment and to combat the emergence of resistant strains. The development of effective and safe nanobead-based interventions can be particularly relevant for increasing the concentrations of antitubercular agents within the infected site and reducing the concentrations in the general circulation, thereby avoiding off-target toxic effects. In this work, rifampicin, a first-line antitubercular agent, was encapsulated into biocompatible and biodegradable polyester-based nanoparticles. In a well-established BALB/c mouse model of pulmonary tuberculosis, the nanoparticles provided improved pharmacokinetics and pharmacodynamics. The nanoparticles were well tolerated and much more efficient than an equivalent amount of free rifampicin. Unlabelled Image [ABSTRACT FROM AUTHOR]

[Display omitted] • Innovative polymer coatings on anodes improve electromediated biofilm eradication. • Coatings catalyze ROS generation or convert hydrophobic surfaces to bactericidal polycations. • Promising efficacy against Staphylococcus aureus biofilms demonstrated. • Addressing critical challenge in medical field: biofilm-associated infections. The formation of biofilm involves cell aggregation and adherence, enveloped by a self-produced extracellular matrix. In the medical domain, biofilm-associated infections pose significant challenges, especially concerning implants. This investigation focuses on enhancing electromediated bacterial biofilm eradication through polymer coatings on the anode. These coatings catalyze reactive oxygen species (ROS) generation or convert hydrophobic coatings to bactericidal hydrophilic polycations, detaching the biofilms that are predominantly polyanionic. The first approach employs a metallized polytetrathienylporphyrin layer with ROS catalytic capability, while the second involves an insoluble hydrophobic polyamide, which, upon oxidation, transforms into a bactericidal hydrolytically degradable polycation. Both approaches show promising efficacy in augmenting electromediated Staphylococcus aureus biofilm destruction. [ABSTRACT FROM AUTHOR]

• HAP NPs were colloidally stabilized with tailored hydrophilic polymers. • NPs were nontoxic and suitable for applications in vivo. • NPs were labeled with fluorescent and radioactive bone-seeking agents in vitro. • NPs were labeled with 99mTc-HEDP in vivo one hour after intravenous injection. The imaging of healthy tissues and solid tumors benefits from the application of nanoparticle probes with altered pharmacokinetics, not available to low molecular weight compounds. However, the distribution and accumulation of nanoprobes in vivo typically take at least tens of hours to be efficient. For nanoprobes bearing a radioactive label, this is contradictory to the requirement of minimizing the radiation dose for patients by using as-short-as-feasible half-life radionuclides in diagnostics. Thus, we developed a two-stage diagnostic concept for monitoring long-lasting targeting effects with short-lived radioactive labels using bone-mimicking biocompatible polymer-coated and colloidally fully stabilized hydroxyapatite nanoparticles (HAP NPs) and bone-seeking radiopharmaceuticals. Within the pretargeting stage, the nonlabeled nanoparticles are allowed to circulate in the blood. Afterward, 99mTc-1-hydroxyethylidene-1.1-diphosphonate (99mTc-HEDP) is administered intravenously for in situ labeling of the nanoparticles and subsequent single-photon emission computed tomography/computed tomography (SPECT/CT) visualization. The HAP NPs, stabilized with tailored hydrophilic polymers, are not cytotoxic in vitro , as shown by several cell lines. The polymer coating prolongs the circulation of HAP NPs in the blood. The nanoparticles were successfully labeled in vivo with 99mTc-HEDP, 1 and 24 h after injection, and they were visualized by SPECT/CT over time in healthy mice. [ABSTRACT FROM AUTHOR]

Bioactive moieties designed to bind to cell membrane receptors benefit from coupling with polymeric carriers that have enhanced affinity to the cell membrane. When bound to the cell surface, such carriers create a "2D solution" of a ligand with a significantly increased concentration near a membrane-bound receptor compared to a freely water-soluble ligand. Bifunctional polymeric carriers based on amphiphilic triblock copolymers were synthesized from 2-pent-4-ynyl oxazoline, 2-nonyl oxazoline and 2-ethyl oxazoline. Their self-assembly and interactions with plasma proteins and HEK 293 cells were studied in detail. The affinity of these triblock copolymers to HEK 293 cell membranes and organ tissues was tunable by the overall hydrophobicity of the polymer molecule, which is determined by the length of the hydrophobic and hydrophilic blocks. The circulation time and biodistribution of three representative triblock copolymers were monitored after intravenous administration to C57BL/6 albino mice. A prolonged circulation time was observed for polymers with longer hydrophobic blocks, despite their molecular weight being below the renal threshold. [Display omitted] • Amphiphilic polyoxazolines are versatile platforms for carrying the bioactive moieties. • Hydrophobicity of polyoxazolines is adjusted by the length of individual blocks. • Affinity of polyoxazolines to proteins and cells is determined by their hydrophobicity. [ABSTRACT FROM AUTHOR]

Multimodal probes, which can be simultaneously visualized by multiple imaging modalities, enable the cellular uptake, intracellular fate, biodistribution and elimination to be tracked in organisms. In this study, we report the synthesis of crystalline WO 3 and CaWO 4 doped with Eu 3+ or Tb 3+ nanoparticles (size range of 10–160 nm) coated with polysaccharides, and these nanoparticles constitute a versatile easy-to-construct modular toolbox for multimodal imaging. The particles adsorb significant amounts of polysaccharides from the solution, providing biocompatibility and may serve as a platform for labeling. For WO 3 , the sorption is reversible. However, on CaWO 4 , stable coating is formed. CaWO 4 /Tb 3+ coated with chemisorbed dextrin, mannan, guar gum and sodium alginate successfully underwent endocytosis with HepG2 cells and was visualized using confocal microscopy. [ABSTRACT FROM AUTHOR]

Motivation: Amyloidoses are diseases caused by the accumulation of normally soluble proteins in the form of insoluble amyloids, leading to the gradual dysfunction and failure of various organs and tissues. Inhibiting amyloid formation is therefore an important therapeutic target. Hypothesis: We hypothesized that mono- and di-gradient amphiphilic copolymers of hydrophilic 2-(m)ethyl-2-oxazoline and hydrophobic 2-aryl-2-oxazolines may inhibit amyloid fibril formation. Experiments: In the model system with hen egg white lysozyme (HEWL) as amyloidogenic protein we determined the effect of these polymers on the amyloid formation by making use of the thioflavin T fluorescence, transmission electron microscopy, isothermal titration calorimetry, and dynamic light scattering. Findings: We found that some gradient copolymers possess very potent concentration-dependent inhibitory effects on HEWL amyloid formation. Structure-activity relationship revealed that copolymers with higher ratios of aromatic monomeric units had stronger amyloid suppression effects, most plausibly due to the combination of hydrophobic and π-π interactions. The measurements also revealed that the polymers that inhibit amyloid formation most plausibly do so in the form of micelles that interact with the growing amyloid fibril ends, not with isolated HEWL molecules in solution. These findings suggest the potential use of these gradient copolymers as therapeutic agents for amyloidoses. [Display omitted] • Some mono- and di-gradient amphiphilic poly(2-oxazoline)s inhibit amyloid formation. • The effect is potent and concentration-dependent in the model hen egg-white lysozyme system. • Higher contents of aromatic units in copolymers lead to higher efficacy. • The polymers likely inhibit amyloid formation by interacting with amyloid fibril ends. [ABSTRACT FROM AUTHOR]

A conceptually new bimodal immunoradiotherapy treatment was demonstrated using thermoresponsive polymer β-glucan- graft -poly(2-isopropyl-2-oxazoline- co -2-butyl-2-oxazoline) bearing complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with yttrium-90(III) at the graft ends. The behavior of this thermoresponsive polymer in aqueous solutions was studied, and it showed the appropriate cloud point temperature for brachytherapy applications. The polymer was tested in vitro , and it exhibited nontoxicity and active uptake into cancer cells and macrophages with colocalization in the lysosomes and macrophagosomes. Moreover, the observed oxidative burst response of the leukocytes established the immunostimulatory properties of the polymer, which were also studied in vivo after injection into the thigh muscles of healthy mice. The subsequent histological evaluation revealed the extensive immune activation reactions at the site of injection. Furthermore, the production of tumor necrosis factor α induced by the prepared polymer was observed in vitro , denoting the optimistic prognosis of the treatment. The biodistribution study in vivo indicated the formation of the polymer depot, which was gradually degraded and excluded from the body. The radiolabeled polymer was used during in vivo antitumor efficiency experiments on mice with EL4 lymphoma. The immunoradiotherapy group (treated with the radiolabeled polymer) demonstrated the complete inhibition of tumor growth during the beginning of the treatment. Moreover, 7 of the 15 mice were completely cured in this group, while the others exhibited significantly prolonged survival time compared to the control group. The in vivo experiments indicated the considerable synergistic effect of using immunoradiotherapy compared to separately using immunotherapy or radiotherapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • First report of employing the electron beam irradiation for preparation of poly(2-oxazoline)-based hydrogel coatings. • Applied method is independent on surface material (Si wafer, PS plate). • Grafting and crosslinking are driven by amount of double bonds essential for the formation of covalent bonds. • Presence of the hydrogel layer decreases cell adhesion to a negligible value. • The stiffness increases with the degree of crosslinking which denotes the possibility of adjusting the required stiffness by proper selection of the experimental parameters. Uncontrolled accumulation of proteins and cells on implantable materials often leads to failure of their performance in vivo. The idea presented in this paper is the use of electron beam irradiation as a widely applicable, cost-effective, and defined method to produce non-biofouling hydrogel coatings to improve the biocompatibility and in vivo performance of implantable materials. Statistical copolymers poly[2-methyl-2-oxazoline-co-2-(3-butenyl)-2-oxazoline]s were deposited on different substrates and irradiated with beta radiation of different radiation doses (2–100 kGy). In the bulk state experiments, we found that the higher content of crosslinkable 3-butenyl units and a higher radiation dose resulted in more efficient crosslinking. Similarly, the irradiation of coatings demonstrated the high impact of the concentration of 3-butenyl units on crosslinking efficiency. Accordingly, the concentration of crosslinkable double bonds in the copolymer is crucial for the stability and homogeneity of the formed hydrogel layer. Stable and uniform hydrogel layers with thicknesses in the micrometer range were prepared from a 5 wt% copolymer solution. Depending on the preparation conditions, the hydrogel layers showed excellent non-biofouling properties with a low number of adherent cells. In addition, stiffness was dependent on the degree of crosslinking, and can thus be tailored for specific application in living tissue. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cationic peptide melittin is efficiently encapsulated into polyanion nanoparticles. • Encapsulation is mainly influenced by the length of the polyanion chain. • In situ encapsulation efficiently suppresses hemolytic toxicity of melittin. • Efficient in unusually low concentrations of micrograms per milliliter. Due to their wide availability, polypeptide/protein venoms produced by certain insects are of high interest as potential active pharmacological ingredients; however, the number of clinical studies on these venoms remains poor. In this paper, we describe an extremely efficient platform to form polyplexes from cationic amphiphilic animal venoms, such as the hemolytic poison melittin. The idea is based on supramolecular melittin cationic charge compensation with nanoparticles (micelles composed of hydrophobic glassy polystyrene core and hydrophilic poly(meth)acrylic acid corona, PMA and PAA acid homopolymers) with high anion charge density at physiological pH. An instant "mix and go" process and efficient melittin complexation with nanoparticles at concentrations down to micrograms per milliliter of PBS solution was achieved and proven by inhibition of melittin-induced hemolysis. We studied in detail how the structural features of the nanoparticles influence their potency; we found that the most important parameter is the number of carboxylates in the polyanion chain (proportional to the molecular weight and length of the anionic poly(meth)acrylic acid block). The poly(meth)acrylic acid-based polymer nanoparticles may be useful as melittin (and possibly other cationic amphiphilic animal venoms) antidotes but also as models for constructing future delivery systems to apply the venoms therapeutically. [ABSTRACT FROM AUTHOR]

Thermoresponsive polymers showing cloud point temperatures (CPT) in aqueous solutions are very promising for the construction of various systems in biomedical field. In many of these applications these polymers get in contact with ionizing radiation, e.g., if they are used as carriers for radiopharmaceuticals or during radiation sterilization. Despite this fact, radiosensitivity of these polymers is largely overlooked to date. In this work, we describe the effect of electron beam ionizing radiation on the physicochemical and phase separation properties of selected thermoresponsive polymers with CPT between room and body temperature. Stability of the polymers to radiation (doses 0-20 kGy) in aqueous solutions increased in the order poly(N-vinylcaprolactam) (PVCL, the least stable) ≪ poly[N-(2,2-difluoroethyl)acrylamide] (DFP) < poly(N-isopropylacrylamide) (PNIPAM) ≪ poly(2-isopropyl-2-oxazoline-co-2-n-butyl-2-oxazoline) (POX). Even low doses of β radiation (1 kGy), which are highly relevant to the storage of polymer radiotherapeutics and sterilization of biomedical systems, cause significant increase in molecular weight due to cross-linking (except for POX, where this effect is weak). In the case of PVCL irradiated with low doses, the increase in molecular weight induced an increase in the CPT of the polymer. For PNIPAM and DFP, there is strong chain hydrophilization leading to an increase in CPT. From this perspective, POX is the most suitable polymer for the construction of delivery systems that experience exposure to radiation, while PVCL is the least suitable and PNIPAM and DFP are suitable only for low radiation demands. [ABSTRACT FROM AUTHOR]

Brachytherapy represents effective local therapy of unresectable solid tumors with very few side effects. Radiolabeled thermoresponsive polymers offer almost noninvasive approach to brachytherapy applications. A radioiodinated, water-soluble, thermosensitive poly( N -vinylcaprolactam) (PVCL) polymer was prepared using two approaches. The direct copolymerization with N -methacryloyl- l -tyrosinamide, as well as end-capping of carboxy-terminated PVCL homopolymer with tyramine, were used. In both cases the product was successfully radiolabeled with 125 I. The obtained polymers demonstrate cloud-point temperature ( T C ) values in the range of 33–35 °C in all the studied solvent systems (water, PBS (pH 7.4) and physiological saline solution). Above the cloud point temperature, the molecularly dissolved polymer is macroprecipitated from the solution. The T C values close to the human body temperature of this biocompatible poly( N -vinylcaprolactam) polymer makes it a promising material intended for local therapy of solid tumors. [ABSTRACT FROM AUTHOR]

Two macrocyclic ligands based on cyclam with trans-disposed N-methyl and N-(4-aminobenzyl) substituents as well as two methylphosphinic (H2 L1) or methylphosphonic (H4 L2) acid pendant arms were synthesised and investigated in solution. The ligands form stable complexes with transition metal ions. Both ligands show high thermodynamic selectivity for divalent copper over nickel(II) and zinc(II)- K(CuL) is larger than K(Ni/ZnL) by about seven orders of magnitude. Complexation is significantly faster for the phosphonate ligand H4 L2, probably due to the stronger coordination ability of the more basic phosphonate groups, which efficiently bind the metal ion in an 'out-of-cage' complex and thus accelerate its 'in-cage' binding. The rate of CuII complexation by the phosphinate ligand H2 L1 is comparable to that of cyclam itself and its derivatives with non-coordinating substituents. Acid-assisted decomplexation of the copper(II) complexes is relatively fast ( τ1/2=44 and 42 s in 1 M aq. HClO4 at 25 °C for H2 L1 and H4 L2, respectively). This combination of properties is convenient for selective copper removal/purification. Thus, the title ligands were employed in the preparation of ion-selective resins for radiocopper(II) separation. Glycidyl methacrylate copolymer beads were modified with the ligands through a diazotisation reaction. The separation ability of the modified polymers was tested with cold copper(II) and non-carrier-added 64Cu in the presence of a large excess of both nickel(II) and zinc(II). The experiments exhibited high overall separation efficiency leading to 60-70 % recovery of radiocopper with high selectivity over the other metal ions, which were originally present in 900-fold molar excess. The results showed that chelating resins with properly tuned selectivity of their complexing moieties can be employed for radiocopper separation. [ABSTRACT FROM AUTHOR]

Wilson's disease is a genetic disorder caused by a malfunction of ATPase 7B that leads to high accumulation of copper in the organism and consequent toxic effects. We propose a gentle therapy to eliminate the excessive copper content with oral administration of insoluble non-resorbable polymer sorbents containing selective chelating groups for copper(II). Polymeric beads with the chelating agents triethylenetetramine, N,N-di(2-pyridylmethyl)amine, and 8-hydroxyquinoline (8HQB) were investigated. In a preliminary copper uptake experiment, we found that 8HQB significantly reduced copper uptake (using copper-64 as a radiotracer) after oral administration in Wistar rats. Furthermore, we measured organ radioactivity in rats to demonstrate that 8HQB radiolabelled with iodine-125 is not absorbed from the gastrointestinal tract after oral administration. Non-resorbability and the blockade of copper uptake were also confirmed with small animal imaging (PET/CT) in mice. In a long-term experiment with Wistar rats fed a diet containing the polymers, we have found that there were no signs of polymer toxicity and the addition of polymers to the diet led to a significant reduction in the copper contents in the kidneys, brains, and livers of the rats. We have shown that polymers containing specific ligands could potentially be novel therapeutics for Wilson's disease. [ABSTRACT FROM AUTHOR]

Highlights: [•] Monodisperse PGMA particles carrying COOH or NH2 groups were developed. [•] Electrophoretic mobilities and ζ potential values of the particles were determined. [•] Poly(glycidyl methacrylate)/Ag nanocomposite microspheres were prepared. [•] The composite microspheres were used as efficient radioiodine scavenger. [Copyright &y& Elsevier]

We built a robust selective potentiometric sensor of reactive oxygen species (ROS) as a thin layer applied on the surface of smart implants, which enables the detection and localization of inflammation at an early stage. The sensor consists of a conductive polymer layer based on polythiophene with an incorporated porphyrin-metal complex that potentiometrically detects the presence of ROS. This sensor is covalently coated with a nonbiofouling layer of poly(2-methyl-2-oxazoline), which works as a biocompatibilizer but mainly prevents the sorption of proteins and other biomacromolecules naturally occurring in organisms, which could interfere with the ROS signal. We have shown that our potentiometric sensor shows a rapid response to hydrogen peroxide, does not experience interference with bovine serum albumin as a model serum protein when sensing ROS, is able to fully reversibly detect ROS with a linear response within a very wide range of biologically relevant concentrations and, most importantly, is able to distinguish between hydrogen peroxide and hypochlorite. We also performed a head-to-head comparison of two positional isomers of thienylated porphyrine for sensor applications (2TTP and 3TTP, with 3TTP shown to be more appropriate) and four different coordinated metals (Cu, Fe, Co and Mn, with Cu and especially Fe shown to be the most appropriate). [Display omitted] • Potentiometric detection of H 2 O 2 in biologically relevant concentration. • Modified metalized polyporphyrine sensing layer. • Nonbiofouling poly(2-alkyl-2oxazoline) layer. [ABSTRACT FROM AUTHOR]

Abstract: Wilson’s disease is a genetic disorder that leads to a high accumulation of copper in multiple organs with subsequent toxic effects. In this paper, a gentle therapy to eliminate harmful copper concentrations in patients with Wilson’s disease is proposed using an oral administration of insoluble polymeric sorbents containing selective chelating groups for copper(II). The sorbents contained triethylenetetramine, N,N-di(2-pyridylmethyl)amine, 8-hydroxyquinoline or 8-hydroxyquinoline-5-sulfonic acid chelating groups bound to a methacrylate-based macroporous support. Nearly quantitative copper(II) uptake within minutes was achieved in buffers modeling the pH range present in the gastric environment (pH 2.0 and 4.0). The sorbents demonstrated chelating selectivity for copper(II) against zinc(II) with ratios of up to 1321. The sorbents demonstrated sufficient stability of the copper complexes against rechelation using studies in a model environment for the small intestine (the presence of chelating amino acids, pH 6.8). [Copyright &y& Elsevier]

Abstract: Polymer conjugates of anticancer drugs have shown high potential for assisting in cancer treatments. The pH-labile spacers allow site-specific triggered release of the drugs. We synthesized and characterized model drug conjugates with hydrazide bond-containing poly[N-(2-hydroxypropyl)methacrylamide] differing in the chemical surrounding of the hydrazone bond-containing spacer to find structure–drug release rate relationships. The conjugate selected for further studies shows negligible drug release in a pH 7.4 buffer but released 50% of the ellipticinium drug within 24h in a pH 5.0 phosphate saline buffer. The ellipticinium drug retained the antiproliferative activity of the ellipticine. [Copyright &y& Elsevier]

[Display omitted] Inflammatory bowel disease (IBD) is a relapsing and remitting inflammatory disease affecting millions of people worldwide. The active phase of IBD is characterized by excessive formation of reactive oxygen species (ROS) in the intestinal mucosa, which further accelerates the inflammatory process. A feasible strategy for the IBD treatment is thus breaking the oxidation-inflammation vicious circle by scavenging excessive ROS with the use of a suitable antioxidant. Herein, we have developed a novel hydrogel system for oral administration utilizing sterically hindered amine-based redox polymer (SHARP) incorporating covalently bound antioxidant SHA groups. SHARP was prepared via free-radical polymerization by covalent crosslinking of 2-hydroxyethyl methacrylate (HEMA), poly(ethylene oxide) methyl ether methacrylate (PEGMA) and a SHA-based monomer, N -(2,2,6,6-tetramethyl-piperidin-4-yl)-methacrylamide. The SHARP hydrogel was resistant to hydrolysis and swelled considerably (∼90% water content) under the simulated gastrointestinal tract (GIT) conditions, and exhibited concentration-dependent antioxidant properties in vitro against different ROS. Further, the SHARP hydrogel was found to be non-genotoxic, non-cytotoxic, non-irritating, and non-absorbable from the gastrointestinal tract. Most importantly, SHARP hydrogel exhibited a statistically significant, dose-dependent therapeutic effect in the mice model of dextran sodium sulfate (DSS)-induced acute colitis. Altogether, the obtained results suggest that the SHARP hydrogel strategy holds a great promise with respect to IBD treatment. [ABSTRACT FROM AUTHOR]

Abstract: Chelating sorbents with diethylenetriaminepenta(methylene-phosphonic acid) (DTPMPA) and ethylenediaminetetraacetic acid ligands immobilized on zirconia matrix were prepared and subsequently saturated with Cu(II). All the Cu chelates catalyzed decomposition of H2O2 yielding highly reactive hydroxyl radicals. All of them were also able to catalyze degradation of polycyclic aromatic hydrocarbons (anthracene, benzo[a]pyrene and benzo[b]fluoranthene). The most effective DTPMPA-based catalysts G-32 and G-35 (10mgml−1 with 100mmol H2O2) caused almost complete decomposition of 15ppm anthracene and benzo[a]pyrene during a five day catalytic cycle at 30°C. Anthracene-1,4-dione was the main product of anthracene oxidation by all catalysts. The catalysts were active in several cycles without regeneration. [Copyright &y& Elsevier]

Abstract: Heterogeneous catalysts based on magnetic mixed iron oxides (MO·Fe2O3; M: Fe, Co, Cu, Mn) were used for the decolorization of several synthetic dyes (Bromophenol Blue, Chicago Sky Blue, Cu Phthalocyanine, Eosin Yellowish, Evans Blue, Naphthol Blue Black, Phenol Red, Poly B-411, and Reactive Orange 16). All the catalysts decomposed H2O2 yielding highly reactive hydroxyl radicals, and were able to decolorize the synthetic dyes. The most effective catalyst FeO·Fe2O3 (25mgmL−1 with 100mmolL−1 H2O2) produced more than 90% decolorization of 50mgL−1 Bromophenol Blue, Chicago Sky Blue, Evans Blue and Naphthol Blue Black within 24h. The fastest decomposition proceeded during the first hour of the reaction. In addition to dye decolorization, all the catalysts also caused a significant decrease of chemical oxygen demand (COD). Individual catalysts were active in the pH range 2–10 depending on their structure and were able to perform sequential catalytic cycles with low metal leaching. [Copyright &y& Elsevier]

Abstract: Chelating sorbents with 8-hydroxyquinoline (IVa), 8-hydroxyquinoline-5-sulfonic acid (IVb), and tris(2-aminoethyl)amine (VI) ligands immobilized on macroporous methacrylate matrix were prepared and saturated with Co(II), Cu(II), and Fe(II). All these chelates catalyze cleavage of H2O2 yielding highly reactive hydroxyl radicals. All were able to degrade by this mechanism polycyclic aromatic hydrocarbons (anthracene, benzo[a]pyrene and benzo[k]fluoranthene). The most effective catalysts IVa-Fe, IVb-Fe, and VI-Cu (25mg with 100μmol H2O2) performed complete decomposition of 33μg anthracene and benzo[a]pyrene during one 7-day catalytic cycle at 25°C. The fastest decomposition proceeded during the 1st day of incubation; 75% of anthracene and 74% of benzo[a]pyrene were decomposed by IVb-Co within the first 24h. More than 25% decomposition within the 1st day was also achieved with IVb-Fe, VI-Cu, IVa-Cu, and VI-Co for anthracene and more than 30% benzo[a]pyrene was decomposed by IVb-Fe, VI-Cu, IVa-Cu, and IVb-Cu during the same period. 1,4-Anthracenedione was the main product of anthracene oxidation by all catalysts. The catalysts were stable at pH 2–11 depending on their structure and able to perform sequential catalytic cycles without regeneration. [Copyright &y& Elsevier]

The use of free lanthanide ions and their complexes for plasmid DNA pBR322 and chromosomal DNA cleavage was studied. Plasmid pBR322 DNA was treated by lanthanide chlorides (Eu3+, La3+, Nd3+, Pr3+, Gd3+) in HEPES buffer (pH 7.0, 7.5 and 8.0) at 24, 37, 50, 63, and 76 °C. The formation of linear and nicked plasmid forms was investigated depending on the reaction conditions. Heterogeneous lanthanide complexes of ethylenediamine tetraacetic acid (EDTA) immobilized on insoluble methacrylate support and iminodiacetic acid (IDA) immobilized on styrene support were used as catalysts plasmid for DNA pBR322 cleavage, too. The temperature of reaction mixture had substantial influence on cleavage rate. The precipitation of DNA occurred during the measurement of interactions between chromosomal DNA and La3+ ions. [Copyright &y& Elsevier]

Here, we report on the construction of biodegradable poly(ethylene oxide monomethyl ether) (MPEO)-b-poly(ε-caprolactone) (PCL) nanoparticles (NPs) having acid-labile (acyclic ketal group) linkage at the block junction. In the presence of acidic pH, the nanoassemblies were destabilized as a consequence of cleaving this linkage. The amphiphilic MPEO-b-PCL diblock copolymer self-assembled in PBS solution into regular spherical NPs. The structure of self-assemble and disassemble NPs were characterized in detail by dynamic (DLS), static (SLS) light scattering, small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). The key of the obtained NPs is using them in a paclitaxel (PTX) delivery system and study their in vitro cytostatic activity in a cancer cell model. The acid-labile ketal linker enabled the disassembly of the NPs in a buffer simulating an acidic environment in endosomal (pH ~5.0 to ~6.0) and lysosomal (pH ~4.0 to ~5.0) cell compartments resulting in the release of paclitaxel (PTX) and formation of neutral degradation products. The in vitro cytotoxicity studies showed that the activity of the drug-loaded NPs was increased compared to the free PTX. The ability of the NPs to release the drug at the endosomal pH with concomitant high cytotoxicity makes them suitable candidates as a drug delivery system for cancer therapy. [ABSTRACT FROM AUTHOR]

Early detection of metastasis is crucial for successful cancer treatment. Sentinel lymph node (SLN) biopsies are used to detect possible pathways of metastasis spread. We present a unique non-invasive diagnostic alternative to biopsy along with an intraoperative imaging tool for surgery proven on an in vivo animal tumor model. Our approach is based on mannan-based copolymers synergistically targeting: (1) SLNs and macrophage-infiltrated solid tumor areas via the high-affinity DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) receptors and (2) tumors via the enhanced permeability and retention (EPR) effect. The polymer conjugates were modified with the imaging probes for visualization with magnetic resonance (MR) and fluorescence imaging, respectively, and with poly(2-methyl-2-oxazoline) (POX) to lower unwanted accumulation in internal organs and to slow down the biodegradation rate. We demonstrated that these polymer conjugates were successfully accumulated in tumors, SLNs and other lymph nodes. Modification with POX resulted in lower accumulation not only in internal organs, but also in lymph nodes and tumors. Importantly, we have shown that mannan-based polymer carriers are non-toxic and, when applied to an in vivo murine cancer model, and offer promising potential as the versatile imaging agents. [ABSTRACT FROM AUTHOR]

In the last half-century, the development of biodegradable polyesters for biomedical applications has advanced significantly. Biodegradable polyester materials containing external stimuli-sensitive linkages are favored in the development of therapeutic devices for pharmacological applications such as delivery vehicles for controlled/sustained drug release. These selectively biodegradable polyesters degrade after particular external stimulus (e.g., pH or redox potential change or the presence of certain enzymes). This review outlines the current development of biodegradable synthetic polyesters materials able to undergo hydrolytic or enzymatic degradation for various biomedical applications, including tissue engineering, temporary implants, wound healing and drug delivery. [ABSTRACT FROM AUTHOR]