Γ-glutamic Acid Research Articles

Polyelectrolyte complex nanofibers from poly(γ-glutamic acid) and fluorescent chitosan oligomer

Polyelectrolyte complex (PEC) nanofibers were fabricated via electrospinning using anionic poly(γ-glutamic acid) (γ-PGA) and cationic fluorescent chitosan oligomer (CHI-O). First, the PEC formation behavior was investigated as a function of the solution concentration, viscosity and blend ratio. The optimum blend ratio and concentration of the anionic γ-PGA and cationic CHI-O for electrospinning was 10/13 (w/w), and continuous nanofibers were obtained at that condition with an average diameter of 370 nm without beads. The resulting PEC nanofibers were chemically crosslinked using glutaraldehyde vapor to provide dimensional stability against water. Confocal microscopy revealed that the fluorescent intensity of the PEC nanofibers increased gradually as the fluorescent CHI-O increased. Also, the fluorescent CHI-O was distributed evenly in the PEC nanofibers through the formation of PEC with anionic γ-PGA. Therefore, the electrospinnability of anionic γ-PGA improved significantly with the PEC formation with cationic CHI-O. This result indicates that anionic biopolymers with a poor electrospinnability can be converted to nanofibers via PEC formation with polycations.

Stereocomplexation Assisted Assembly of Poly(γ-glutamic Acid)-graft-polylactide Nano-micelles and Their Efficacy as Anticancer Drug Carrier.

Micelles as drug carriers are characterized by their inherent instability due to the weak physical interactions that facilitate the self-assembly of amphiphilic block copolymers. As one of the strong physical interactions, the stereocomplexation between the equal molar of enantiomeric polylactides, i.e., the poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), may be harnessed to obtain micelles with enhanced stability and drug loading capacity and consequent sustained release. In this paper, stereocomplexed micelles gama-PGA-g-PLA micelles) were fabricated from the stereocomplexation between poly(gama-glutamic acid)-graft-PLLA gama-PGA-g-PLA) and poly(gamaglutamic acid)-graft-PDLA gama-PGA-g-PLA). These stereocomplexed micelles exhibited a lower CMC than the corresponding enantiomeric micelles. Furthermore, they showed higher drug loading content and drug loading efficiency in addition to more sustained drug release profile in vitro. In vivo imaging confirmed that the DiR-encapsulated stereocomplexed gama-PGA-g-PLA micelles can deliver anti-cancer drug to tumors with enhanced tissue penetration. Overall, gama-PGA-g-PLA micelles exhibited greater anti-cancer effects as compared with the free drug and the stereocomplexation may be a promising strategy for fabrication of anti-cancer drug carriers with significantly enhanced efficacy.

Anionic polypeptide poly(γ-glutamic acid)-functionalized magnetic Fe3O4-GO-(o-MWCNTs) hybrid nanocomposite for high-efficiency removal of Cd(II), Cu(II) and Ni(II) heavy metal ions

A novel hybrid adsorbent, anionic polypeptide poly(γ-glutamic acid)—(γ-PGA) functionalized magnetic Fe3O4-GO-(o-MWCNTs) hybrid nanocomposite was successfully prepared via a simple one-pot reaction. The as-prepared γ-PGA-Fe3O4-GO-(o-MWCNTs) composites were characterized via SEM, TEM, FTIR, XRD, TGA, AFM, zeta potential analysis and magnetic properties analysis. The results indicate that the addition of o-MWCNTs solves the serious aggregation problem of GO and thus makes the GO exposed more grafted sites bonded to large amount of γ-PGA molecule chains. The prepared γ-PGA-Fe3O4-GO-(o-MWCNTs) composites not only have a higher specific surface area to offer abundant surface adsorption sites, but also can be separated more easily from solution systems. Furthermore, the adsorption tests of the γ-PGA-Fe3O4-GO-(o-MWCNTs) were analyzed in Cd(II), Cu(II) and Ni(II) solutions at various pH values, contact time, and initial concentrations of ions. This work indicates that the hybrid adsorbent can be the suitable absorbent materials for various types of heavy metal ions pollution removal and exhibit higher adsorbing capacities in the pH range of 2–10. Its maximum removal capacity calculated by Langmuir model under the optimal conditions toward Cd(II), Cu(II) and Ni(II) is 625.00, 574.71 and 384.62 mg/g, respectively. The adsorption process was well described by the pseudo-second-order kinetics model and the Langmuir isotherm model, respectively. The adsorption mechanism may involve characteristic coordination bonding and electrostatic attraction between γ-PGA-Fe3O4-GO-(o-MWCNTs) and metal ions. Additionally, anionic polypeptide γ-PGA-Fe3O4-GO-(o-MWCNTs) composite can be easily regenerated and recycled at least for three adsorption–desorption recycles. The unique characteristics render the composite highly promising as an advanced adsorbent material for the removal of heavy metal ions.

Effect of immobilization of poly(γ-glutamic acid) on the biocompatibility of electrospun poly (L-lactide) mats

In this study, poly(L-lactide) (PLLA) non-woven mats were prepared by electrospinning technique, followed by treating with oxygen plasma and grafting with 3-aminopropyl triethoxysilane (APTES), then immersed in poly(γ-glutamic acid) (γ-PGA) solution to form a layer of γ-PGA on the surface. In so doing, hydrophobic PLLA would become highly hydrophilic. Through characterization of hydrophilicity and biocompatibility, the feasibility of these modified mats for wound dressing was evaluated. The results show that after the grafting of γ-PGA, the swelling ratio increased greatly from 7% for pristine PLLA mat to 321% for γ-PGA-grafted PLLA mat, and the contact angle decreased from 112° to 25°. In vitro cytocompatibility tests against L929 fibroblast show that γ-PGA-grafted PLLA was non-cytotoxic. In addition, the proliferation of fibroblasts was higher on γ-PGA-grafted PLLA than on pristine PLLA.

Enzymatic preparation of functional polysaccharide hydrogels by phosphorylase catalysis

Abstract This article reviews enzymatic preparation of functional polysaccharide hydrogels by means of phosphorylase-catalyzed enzymatic polymerization. A first topic of this review deals with the synthesis of amylose-grafted polymeric materials and their formation of hydrogels, composed of abundant natural polymeric main-chains, such as chitosan, cellulose, xantham gum, carboxymethyl cellulose, and poly(γ-glutamic acid). Such synthesis was achieved by combining the phosphorylase-catalyzed enzymatic polymerization forming amylose with the appropriate chemical reaction (chemoenzymatic method). An amylose-grafted chitin nanofiber hyrogel was also prepared by the chemoenzymatic approach. As a second topic, the preparation of glycogen hydrogels by the phosphorylase-catalyzed enzymatic reactions was described. When the phosphorylase-catalyzed enzymatic polymerization from glycogen as a polymeric primer was carried out, followed by standing the reaction mixture at room temperature, a hydrogel was obtained. pH-Responsive amphoteric glycogen hydrogels were also fabricated by means of the successive phosphorylase-catalyzed enzymatic reactions.

Preparation of supramolecular network materials by means of amylose helical assemblies

Amylose, a natural polysaccharides, is a well-known functional material, because it forms double helix and inclusion complex assemblies depending on whether guest compounds are present or not, owing to its left-handed helical conformation. Amylose is precisely synthesized by phosphorylase-catalyzed enzymatic polymerization. In this study, we investigated the phosphorylase-catalyzed enzymatic polymerization initiated from maltoheptalose (primer for the polymerization)-grafted poly(γ-glutamic acid) in the presence of different feed ratios of a guest polymer, poly(ε-caprolactone) (PCL). In the absence of PCL or presence of less amount of PCL, the reaction mixtures totally turned into hydrogel form, predominantly composed of amylose double helixes. On the other hand, aggregates, which were largely composed of amylose inclusion complexes, were formed in the reaction mixtures in the presence of larger amount of PCL. The analytical results indicated that double helix cross-linking points participated into the formation of larger network structure, whereas smaller network structure was fabricated from inclusion complex cross-linking points. These structures on molecular level hierarchically constructed different macroscopic network sizes, leading to difference in the material forms.

Injectable collagen/RGD systems for bone tissue engineering applications.

Imbalance crosslink density and polymer concentration gradient is formed within the traditional alginate hydrogel using calcium chloride as a crosslinking agent in external gelation for instantaneously process. In this studying, type I collagen (Col I) blended calcium salt form of poly(γ-glutamic acid) (γCaPGA) was mixing with RGD-modified alginate with convenient gelation process and suitable for practical use. The hydrophilicity of the resulting hydrogels was evaluated through swelling tests, water retention capacity tests, and water vapor permeation tests. Mineralization was qualitatively evaluated by alizarin red dyeing at day 14, verifying the deposition of calcium. The in vitro osteogenic differentiation is monitored by determining the early and late osteocalcin (OCN) and osteopontin (OPN) markers with MG63 cells. Obtained results demonstrated that no extremely changes in mechanical properties. After 14 days of culture, hydrogels significantly stimulated OCN/OPN gene expressions and MG63 cell proliferation. Unusually, γCaPGA with RGD-modified alginate appeared better calcium deposition in 14 days than the other. However, addition of Col I can counterpoise RGD effect in blood coagulation and platelet adhesion made the hydrogel more flexibility and selectively in use. This studying provided that non-covalently crosslinked hydrogel by γCaPGA with alginate can be upgrading by RGD and Col I in water uptake capability, obviously effective for MG63 cells and are remarkably biocompatible and exhibited no cytotoxicity. Moreover, results also displayed the injectable process without complicated procedure, have high cost/performance ratio and have great potential for bone regeneration.

Fluorescence studies on the aggregation behaviors of collagen modified with NHS-activated poly(γ-glutamic acid)

The poly(γ-glutamic acid)-NHS (γ-PGA-NHS) esters were used to endow collagen with both of excellent water-solubility and thermal stability via cross-linking reaction between γ-PGA-NHS and collagen. In the present work, the effect of γ-PGA-NHS on the aggregation of collagen molecules was studied by fluorescence techniques. The fluorescence emission spectra of pyrene in collagen solutions and the intrinsic fluorescence emission spectra of collagen suggested different effects of γ-PGA-NHS on collagen molecules: inhibiting aggregation below critical aggregation concentration (CAC) and promoting aggregation above CAC. The two-dimensional (2D) fluorescence correlation spectra indicated that the intermolecular hydrogen bonding and cross-linking between γ-PGA-NHS and collagen would influence the aggregation of collagen molecules. By the ultra-sensitive differential scanning calorimeter (VP-DSC), it was found that the main denaturational transition temperature (Tm2) of modified collagen increased, while its calorimetric enthalpy changes (ΔH2) decreased compared to those of native collagen, further indicating that the modification of γ-PGA-NHS influenced the aggregation of collagen molecules. The study provide useful information for the utilizing and or the processing of water-soluble collagen in aqueous solution in the fields such as cosmetics, health care products, tissue engineering and biomedical materials, etc.

A self-healing conductive and stretchable aligned carbon nanotube/hydrogel composite with a sandwich structure.

Self-healing conductive elastomers have emerged as a class of novel materials that are important for fabricating human-motion sensors, soft robots and healthcare monitoring systems. Herein, we report on a hydrogel of modified poly(γ-glutamic) acid polymer chains crosslinked by coordination complexes, which exhibits good stretchability (1375%), long-term stability (more than 40 days), and self-healing ability (99.0 ± 1.5% in 3 h). Furthermore, a "sandwich" structure composite was fabricated, which is composed of self-healing hydrogels and Au nanograin-decorated aligned multiwall carbon nanotube sheets. It possesses fast self-healing ability, a low stable electronic resistance of 10 ± 1 Ω sq-1, in the temperature range of -40-90 °C, the humidity range of 10-90%, and a stretching range up to 200%.

Antibacterial Films Made of Ionic Complexes of Poly(γ-glutamic acid) and Ethyl Lauroyl Arginate

The biocide agent LAE (ethyl αN-lauroyl l-arginate chloride) was coupled with poly(γ-glutamic acid) (PGGA) to form stable ionic complexes with LAE:PGGA ratios of 1 and 0.5. The nanostructure adopted by these complexes and its response to thermal changes were examined in detail by Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) using synchrotron radiation in real time. A layered biphasic structure with LAE filling the space between the polypeptidic sheets was adopted in these complexes. The complexes were stable up to above 250 °C, non-water soluble, and were able to form consistent transparent films. The release of LAE from the complexes upon incubation in aqueous buffer was examined and found to depend on both pH and complex composition. The antibacterial activity of films made of these complexes against Gram-positive (L. monocytogenes and S. aureus) and Gram-negative (E. coli and S. enterica) bacteria was preliminary evaluated and was found to be very high against the formers and only moderate against the later. The bactericide activity displayed by the LAE·PGGA complexes was directly related with the amount of LAE that was released from the film to the environment.

Characterization and analytical development for amphiphilic poly(γ-glutamic acid) as raw material of nanoparticle adjuvants

Amphiphilic graft copolymer consisting of poly(γ-glutamic acid) (γ-PGA) as the hydrophilic backbone and L-phenylalanine ethyl ester (Phe) as the hydrophobic side chain is an important biodegradable polymer with great potential in medical applications. In this research, we established analytical methods for the characterization and quality control of γ-PGA-graft-Phe (γ-PGA-Phe), which forms nanoparticles in aqueous solution, as a deployment platform in practical applications for vaccine adjuvants. The SEC-RI/MALS system, which uses size exclusion chromatography (SEC) coupled with a multi_angle light scattering (MALS) detector and refractive index (RI) detector, was developed to evaluate the characteristics of various types of polymers. By this method, it was indicated that absolute molecular weight (MW) should be used to measure the branch polymer. A gradient reversed phase HPLC (RP-HPLC) method was developed for the content of γ-PGA-Phe and the impurity levels to control product quality and safety. This quantitative approach could become key elements for identifying and characterizing γ-PGA-Phe. In addition, the degradation mechanism of γ-PGA-Phe was also identified as cleavage of main-chain of γ-PGA-Phe based on the stability study of γ-PGA-Phe in buffer solution with various pH values. The analytical developments described above will be important for use in both characterization and formulation design of biopolymers. Nanoparticles (NPs) composed of well-characterized biodegradable γ-PGA-Phe are expected to have a variety of potential clinical applications such as their use as drug and vaccine carriers.

A gold electrode modified with a nanoparticulate film composed of a conducting copolymer for ultrasensitive voltammetric sensing of hydrogen peroxide.

A film consisting of poly(γ-glutamic acid) modified with 3-aminothiophene (ATh-γ-PGA) was prepared by macromolecular self-assembly and electropolymerization. ATh-γ-PGA is amphiphilic and electrically conductive. The copolymers undergo self-assembly to form nanoparticles (NPs) on decreasing the pH value of an aqueous solution. A conducting film of NPs was formed on the surface of a gold electrode by casting the ATh-γ-PGA NPs and subsequently electropolymerizing the thiophene units. Next, horseradish peroxidase and Nafion were cast onto the film to obtain an enzymatic biosensor for H2O2. Due to the electropolymerization step, a cross-conjugated polymer network is created that improves electron transfer rates and thus enhances the response. This endows the biosensor with high sensitivity. Two linear ranges are present, the first ranging from 1 × 10-11 to 1 × 10-8mol·L-1, and the second from 1 × 10-8 to 1 × 10-5mol·L-1. The detection limit is as low as 3 × 10-12mol·L-1. The sensor is stable, repeatable, and was successfully applied to the determination of H2O2 in a commercial disinfecting solution. Graphical abstract Preparation of a conducting nanoparticle (NP) film on the gold electrode (GE) by self-assembly of poly(γ-glutamic acid) that was modified with electroactive 3-aminothiophene (ATh-γ-PGA). It servedas a platform for thefabricationof an ultrasensitive voltammetric enzyme-based biosensor for H2O2.

Surfing as a risk factor for sensitization to poly(γ-glutamic acid) in fermented soybeans, natto, allergy

BackgroundPoly(γ-glutamic acid) (PGA) is an allergen in natto, fermented soybeans, which causes late-onset anaphylaxis. We hypothesized that jellyfish stings sensitize adults to PGA because a surfer had allergies to both natto and jellyfish, whose sting contains PGA. The aim of the study was to identify behavioral factors, such as marine sports, associated with PGA sensitization. MethodsOutpatients diagnosed with food allergies based on relevant clinical history, positive skin test and/or food challenge test answered a questionnaire during a regular visit in 2016. ResultsQuestionnaire data from 140 outpatients were analyzed. These patients were divided into two groups: natto allergy group (13 patients, M:F = 10:3, mean age 40.6 years) and non-natto allergy group (127 patients, M:F = 46:81, mean age 44.5 years). All patients with natto allergy had positive results in skin prick test and basophil activation test with PGA. Of these, 92.3% had a marine sport hobby, especially surfing (84.6%). PGA sensitization was independently associated with marine sports (odds ratio, 278.0, 95 percent confidence interval, 36.9–6315.9, p < 0.001) adjusted for male sex and sea bathing, but not with male sex or sea bathing. In addition, although there was no significant difference in the experience of marine sports between natto and non-natto allergy groups, the natto allergy group participated significantly more frequently in marine sports than the non-natto allergy group (p < 0.001). There was no significant difference between natto consumption amount and PGA sensitization. ConclusionsSurfing is a risk factor for PGA sensitization in those with allergy to natto.

A novel strategy to fabricate water-soluble collagen using poly(γ-glutamic acid)-derivatives as dual-functional modifier

Native collagen cannot be dissolved in neutral pH buffer, limiting its application in many fields. The traditional method to prepare water-soluble collagen is succinylation modification, which causes the decrease in the thermal stability. Therefore, poly(γ-glutamic acid)-N-hydroxysuccinimide (γ-PGA-NHS) esters were used as a novel modifying agent of collagen. FTIR results indicated the intact retention of native triple-helix structure after modification. Isoelectric point of the modified collagens shifted continuously to lower values with increasing the γ-PGA-NHS/collagen ratios (w/w). Consequently, the modified collagen can form a clear solution in neutral pH buffer. Furthermore, the denaturation temperature (Td) of the modified collagens reached 44.8–49.9°C, which were 6.0–11.1°C higher than that of native collagen. However, it should be noted that gelation occurred when modifier/collagen ratio (w/w)=50% as γ-PGA-NHS with a relatively high esterification degree was used. As a whole, these results indicated that dual-functional modification in regards to both of water solubility and thermal stability on collagen can be achieved using γ-PGA-NHS esters with a relatively low esterification degree. In addition, the proliferation of fibroblasts could be promoted as reflected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and 4′,6-diamidino-2-phenylindole (DAPI) method, suggesting the excellent cytocompatibility of the modified collagens. The present study provided useful information to the design of novel water-soluble collagen, which could be applied in the fields including biomaterials, cosmetics etc.

Combined delivery of bone morphogenetic protein-2 and insulin-like growth factor-1 from nano-poly (γ-glutamic acid)/β-tricalcium phosphate-based calcium phosphate cement and its effect on bone regeneration invitro.

In this study, nano-doped calcium phosphate cement delivery systems (poly (γ-glutamic acid)/β-tricalcium phosphate/calcium phosphate ceramics and nano (γ-glutamic acid)/β-tricalcium phosphate/calcium phosphate ceramic) were fabricated, and low doses (10 µg/g) of two growth factors, insulin-like growth factor-1 and bone morphogenetic protein-2, were encapsulated then sequentially released. We characterized the delivery systems using Fourier transform infrared spectroscopy and X-ray diffraction and measured washout resistance and compressive strength, and thus optimized the most appropriate proportioning of delivery systems for the two growth factors. One of the growth factors was absorbed by the nano-poly (γ-glutamic acid)/β-tricalcium phosphate, which was then mixed into the calcium phosphate ceramic solid phase to create a new solid phase calcium phosphate ceramic. Nano-poly (γ-glutamic acid)/β-tricalcium phosphate/calcium phosphate ceramic carriers were then prepared by blending the new calcium phosphate ceramic solid phase powder with a solution of the remaining growth factor. The effects of different release patterns (studying sequential behavior) of insulin-like growth factor-1 and bone morphogenetic protein-2 on osteogenic proliferation and differentiation of the MC3t3-E1 mouse osteoblast cell were investigated. This combinational delivery system provided a controlled release of the two growth factors, in which nano-doping significantly affected their release kinetics. The incorporation of dual growth factors could potentially stimulate bone healing and promoting bone ingrowth processes at a low dose.

A composite hydrogel of chitosan/heparin/poly (γ-glutamic acid) loaded with superoxide dismutase for wound healing

In chronic wounds, severe oxidative stress hampers the healing of wounds. This study constructed a novel antioxidant-loaded hydrogel for healing diabetic wounds. First, composite hydrogels consisting of chitosan, heparin and poly (γ-glutamic acid) with different ratios were prepared through electrostatic interaction. These hydrogels exhibited good three-dimensional network structures, and the porosity of the hydrogels decreased as the crosslinking density increased. The hydrogels possessed good swelling capacity, and showed typical viscoelastic behavior and good mechanical property in rheological test. Fibroblast proliferation assay demonstrated that the hydrogels were cytocompatible. Then, superoxide dismutase was loaded onto the hydrogel to build a wound dressing with antioxidant property. In diabetic rat models, the dressing proved to accelerate wound healing by promoting wound closure and collagen deposition. In summary, the hydrogel prepared in this study exhibited good physical properties and could promote the repair of chronic trauma in diabetes effectively and therefore is a promising candidate dressing in wound healing.

Aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and multiple arms of the innate immune response in lymph nodes.

In this study, we suggest a designer vaccine adjuvant that can mimic the drainage of pathogens into lymph nodes and activate innate immune response in lymph nodes. By the amination of multivalent carboxyl groups in poly-(γ-glutamic acid) (γ-PGA) nanomicelles, the size was reduced for rapid entry into lymphatic vessels, and the immunologically inert nanomicelles were turned into potential activators of inflammasomes. Aminated γ-PGA nanomicelles (aPNMs) induced NLRP3 inflammasome activation and the subsequent release of proinflammatory IL-1β. The NLRP3-dependent inflammasome induction mechanism was confirmed through enzyme (cathepsin B and caspase-1) inhibitors and NLRP3 knockout mice model. After the aPNMs were combined with a clinically evaluated TLR3 agonist, polyinosinic–polycytidylic acid sodium salt (aPNM-IC), they triggered multiple arms of the innate immune response, including the secretion of pro-inflammatory cytokines by both inflammasomes and an inflammasome-independent pathway and the included type I interferons.

Injectable system and its potential application for the delivery of biomolecules by using thermosensitive poly(γ-glutamic acid)-based physical hydrogel

Poly (γ-glutamic acid) (PGA) is a natural biomaterial with numerous good properties such as non-toxicity, non-immunogenicity, and water holding. So, various forms of PGA-based materials have been developed for bio-applications, including sheet, cross-linked hydrogel, and nanoparticle except injectable hydrogel type. Considering inherent advantages of injectable system, injectable hydrogel based on PGA can broaden the bio-application range of PGA. In this study, a PGA-based injectable hydrogel system was prepared by physically mixing it with a small amount of chitosan with two different water solubility and molecular weight. The prepared hydrogel system showed a thermo-sensitivity through sol-gel transition behavior in the body temperature change. The mechanical properties and in vitro stability could be modulated by varying the ratio of two types of chitosan. In vitro protein (human bFGF) delivery using this injectable formulation showed a sustained release for ∼2 weeks while preserving its bioactivity. In addition, the in situ formation of this PGA-based hydrogel formulation upon subcutaneous injection was demonstrated in vivo. The hydrogel formed in vivo also showed a long term (∼2 weeks) stability without noticeable inflammatory response. Therefore, the present formulation can be applied as a promising injectable hydrogel system for tissue engineering or drug delivery.

Injectable hydrogels based on the hyaluronic acid and poly (γ-glutamic acid) for controlled protein delivery

Injectable hydrogels have great potential in minimally invasive delivery. In this work, novel injectable hydrogels were prepared via self-crosslinking of aldehyde hyaluronic acid (HA-CHO) and hydrazide-modified poly (γ-glutamic acid) (γ-PGA-ADH) for proteins delivery. The HA/γ-PGA hydrogels could be formed in situ as fast as 9s with high swelling ratios. Rheological properties illustrated a wide processing range and good mechanical properties, which were reflected by broad linear viscoelastic region and higher threshold shear stress (σc) and storage modulus (G′). Meanwhile, the gelation time, swelling ratio, rheological properties, as well as the protein release behavior could be modulated conveniently. Bovine serum albumin (BSA) was designed as a model drug to study the release behavior. We found that the release mechanisms were either diffusion or Case-II relaxation depending on the different hydrogel components. The HA/γ-PGA hydrogels also showed good biocompatibility. Therefore, the HA/γ-PGA hydrogels have great potential as promising injectable biomaterials for controlled protein delivery.

Pro-inflammatory chitosan/poly(γ-glutamic acid) nanoparticles modulate human antigen-presenting cells phenotype and revert their pro-invasive capacity.

The immune system is responsible to detect and destroy abnormal cells preventing the development of cancer. However, the immunosuppressive tumor microenvironment can compromise the immune response favoring tumor progression. Thus, immune system modulation towards an immunostimulatory profile can improve anticancer therapies. This research focus on the development of chitosan/poly(γ-glutamic acid) nanoparticles (NPs) to modulate human antigen-presenting cells (APCs) phenotype and to counteract their pro-invasive capacity. Interestingly, Ch/γ-PGA NPs had a prominent effect in inducing macrophages and dendritic cells immunostimulatory phenotype, thus favoring T cell proliferation and inhibiting colorectal cancer cell invasion. We propose that their combination with other immunomodulatory drugs or conventional anticancer therapies can improve patients' outcome.