pH-responsive Characteristics Research Articles

Eco-friendly, pH-sensitive curcumin-loaded sodium alginate/hydroxyapatite/quaternary ammonium chitosan microspheres with enhanced antibacterial and antioxidant activities for fruit preservation

The development of intelligent responsive reactive packaging materials with natural polymers shows excellent potential in food preservation. In this study, eco-friendly, pH-sensitive sodium alginate (SA)/hydroxyapatite (HA)/quaternary ammonium chitosan (HACC) composite microspheres loading curcumin (CUR) with excellent antibacterial and antioxidant activities were successfully synthesized. Scanning electron microscopy (SEM) and nitrogen adsorption/desorption tests indicated that the doping of HA substantially increased the specific surface area and pore volume of the microspheres. The loading experiments showed that the efficiency of the microspheres was significantly increased by 49.47 % and 55.10 %, respectively, when HA and HACC were incorporated into the SA network. The release test results suggested that the release rate of SA/HA/HACC microspheres loading CUR (SA/HA/HACC@CUR) increased as the pH decreased, demonstrating notable pH-responsive release characteristics. DPPH free radical scavenging experiments demonstrated that the SA/HA/HACC@CUR had excellent and long-lasting antioxidant capacity. The antibacterial experiments revealed that the SA/HA/HACC@CUR had excellent antibacterial properties, with inhibition rates of 88.73 % and 92.52 % against E. coli and S. aureus, respectively. Making coatings out of microspheres could effectively slow down the rotting and deterioration of cherry tomatoes during storage, suggesting that microspheres with intelligent responses have a broad application prospect in fruit preservation.

PH-Responsive Rhodamine Nanotube Capable of Self-Reporting the Assembly State.

Nanomaterials that respond to intracellular signals, such as pH, have the potential for many biomedical applications, such as drug delivery, because the assembly/disassembly process can be tailored to respond to a stimulus characteristic of a specific subcellular location. In this work, two rhodamine-peptides that form stable nanotubes at physiological pH but dissociate into highly fluorescent monomers within the acidified interior of endosomal/lysosomal cellular compartments have been developed. The rhodamine dipeptide conjugates, NH2-KK(RhB)-NH2 (RhB-KK) and NH2-EK(RhB)-NH2 (RhB-KE) with rhodamine B chromophores appended at the ε-amino position of a lysine residue, were shown to assemble into well-defined nanotubes at pH values above ∼4-5 and to dissociate into a fluorescent monomer state at lower pH values. The pH dependence of the assembly process was investigated using circular dichroism (CD) and fluorescence spectroscopy along with transmission electron microscopy (TEM), atomic force microscopy (AFM), and confocal imaging. Although the ring opening/closing transition of the rhodamine chromophore took place at pH 4.1 for both peptides, the onset of assembly began at pH 4.6 for RhB-KE and at a comparatively more basic pH (5.8) for RhB-KK. Accordingly, the rhodamine-peptides interconverted between three pH-dependent states: an open-ring, monomeric state (λmax 580 nm, λex 550 nm) at pH values at or below ∼4.6; a closed-ring, nanotube form that exhibits AIEE (λmax 460 nm, λex = 330 nm) at higher pH values; a closed-ring, nonemissive monomeric state that emerged below the critical micelle concentrations (CMC). The pH-responsive features of the peptides were evaluated by live-cell imaging in three cancer cell lines using confocal laser scanning microscopy (CLSM). Visualizing the cells after incubation with either RhB-KE or RhB-KK produced CLSM images with a punctate appearance in the Texas Red channel that colocalized with the lysosomes. These experiments indicate that the nanotubes were rapidly trafficked into the acidic lysosomal compartments within the cells, which induced dissociation into a monomeric, open state. Uptake inhibition studies suggested that cellular uptake was mediated by either caveolae- or clathrin-mediated endocytosis, depending on the cell line studied.

Self-assembly metal phenolic network coating improves the controlled release and bacteriostatic properties of Litsea cubeba essential oil-loaded ε-polylysine-pectin nanoparticles

Pectin and ε-polylysine (ε-PL) nanoparticles loaded with Litsea cubeba essential oil (LEO) (PP-LNPs) were prepared through the electrostatic interaction. Metal phenol network (MPN) coatings, designated as MPN@PP-LNPs, were fabricated on the surface of the nanoparticles via self-assembly process of tannic acid (TA) and FeIII to develop food preservative materials with pH-responsive controlled release. The morphology, encapsulation efficiency, and pH-responsive release characteristics of MPN@PP-LNPs were investigated. The results showed that the particle size of MPN@PP-LNPs was 432.5 ± 58.6 nm. Furthermore, the encapsulation efficiencies of ε-PL and LEO were 83.26 ± 2.21% and 30.78 ± 3.92%, respectively. TA was rapidly released at low pH, while LEO exhibited controlled release over a wide pH range (pH 1.2–9.0). In addition, the MPN coating has been demonstrated to enhance antioxidant activity and inhibit the growth of E. coli and S. aureus under acidic conditions. Furthermore, preliminary evidence suggests that MPN@PP-LNPs are not cytotoxic. In conclusion, MPN@PP-LNPs, prepared through the self-assembled surface modification of TA and FeIII, was an effective material for food preservation.

Construction of a MoS2@mSiO2 nanocarrier as a near-infrared/pH dual-responsive platform to control the drug release for anti-tumor

Designing new-type nanosystems to realize the combination of multiple treatment is an efficient routine to enhance the anti-tumor efficacy in clinic. In this study, molybdenum disulfide (MoS2) was selected as a photothermal agent, and mesoporous silica (mSiO2) was coated on the surface of MoS2 using the solvothermal and template removal methods. The chemotherapeutic drug doxorubicin hydrochloride (DOX) as a model drug was then loaded into the above MoS2@mSiO2 nanocarrier to prepare the tumor-targeting MoS2@mSiO2-DOX nanosystem. XRD, UV–Vis, FTIR, SEM, TEM, and DLS results jointly confirmed that the MoS2@mSiO2-DOX nanosystem with a particle size of approximately 370 nm was successfully synthesized. The XPS and BET analysis identified that the outer layer of MoS2@mSiO2 nanocarrier was SiO2, which has a large surface area of 99.41 m2/g with an average pore size of 3.5 nm coated on the MoS2. The in-vitro cytotoxicity and photothermal performance of the MoS2@mSiO2 nanodrug delivery system was tested, and the results show that MoS2@mSiO2 has a low toxicity to normal human liver cells (HL-7702), and which also exhibits a good photothermal stability with a photothermal conversion efficiency of 28.8%. With the aid of the large specific surface area of mSiO2 and the opposite zeta potential, a high amount of DOX was loaded on MoS2@mSiO2 nanocarrier, and the measured loading efficiency of DOX can reach up to 48.87%. The 48 h-drug release rate of MoS2@mSiO2-DOX reaches 35.65% under the conditions of near infrared (NIR) laser irradiation at pH=5.0, which is nearly 5 times higher than that of 6.26% under the normal physiological environment (pH=7.4 without NIR laser irradiation), indicating that the MoS2@mSiO2-DOX nanosystem possesses obvious pH and NIR laser responsive release characteristics. The MoS2@mSiO2 nanocarrier has good cytocompatibility, outstanding photothermal conversion and drug loading properties, and after DOX adsorption, the system exhibits excellent pH and laser responsive drug controlled release performance, which is expected to be widely used in the field of combining the photothermal-chemotherapy to synergistically resist tumor.

Smart hydrogel catalyst with tunable activity for 4-nitrophenol reduction at different temperatures and pH

In this study, a novel method is introduced for preparing the poly (N-isopropylacrylamideco-methacrylic acid) (PNIPAM) hydrogel catalyst (PNMC-Ag) with embedded silver nanoparticles (Ag NPs), by employing in situ reduction of Ag+ in polymeric network. The prepared hydrogel catalyst exhibits both thermal and pH responsiveness, facilitating precise control of catalytic efficiency in reducing pollutants such as 4-nitrophenol (4-NP) under varying environmental conditions. The embedded Ag NPs demonstrate remarkable stability against self-aggregation due to their confinement within the polymeric network, thus maintaining their exceptional catalytic performance over time. Leveraging the dual-responsive nature of the PNMC-Ag catalyst, tunable catalytic activity can be achieved by adjusting the temperature and pH of the reaction environment. Specifically, the Ag NPs-hydrogel catalyst exhibits high catalytic activity (21 min, 98.5%) in low-temperature ([Formula: see text]< 32°C) at neutral pH and alkaline (pH = 9) conditions at room temperature, while its activity is attenuated in high-temperature ([Formula: see text]> 32°C) at neutral pH or acidic (pH [Formula: see text]4) environments at room temperature owing to the hydrogel’s thermal and pH-responsive characteristics. This distinctive feature enables precise control over the catalytic reaction, offering an effective approach for the removal of 4-NP from wastewater using a noble-metal-containing stimuli-responsive hydrogel (SRH) catalyst. Overall, this work represents a significant step towards the development of intelligent catalytic materials with superior environmental remediation capabilities.

Extracellular Matrix Mimicking Wound Microenvironment Responsive Amyloid-Heparin@TAAgNP Co-Assembled Hydrogel: An Effective Conductive Antibacterial Wound Healing Material.

Bioengineered composite hydrogel platforms made of a supramolecular coassembly have recently garnered significant attention as promising biomaterial-based healthcare therapeutics. The mechanical durability of amyloids, in conjunction with the structured charged framework rendered by biologically abundant key ECM component glycosaminoglycan, enables us to design minimalistic customized biomaterial suited for stimuli responsive therapy. In this study, by harnessing the heparin sulfate-binding aptitude of amyloid fibrils, we have constructed a pH-responsive extracellular matrix (ECM) mimicking hydrogel matrix. This effective biocompatible platform comprising heparin sulfate-amyloid coassembled hydrogel embedded with polyphenol functionalized silver nanoparticles not only provide a native skin ECM-like conductive environment but also provide wound-microenvironment responsive on-demand superior antibacterial efficacy for effective diabetic wound healing. Interestingly, both the cytocompatibility and antibacterial properties of this bioinspired matrix can be fine-tuned by controlling the mutual ratio of heparin sulfate-amyloid and incubated silver nanoparticle components, respectively. The designed biomaterial platform exhibits notable effectiveness in the treatment of chronic hyperglycemic wounds infected with multidrug-resistant bacteria, because of the integration of pH-responsive release characteristics of the incubated functionalized AgNP and the antibacterial amyloid fibrils. In addition to this, the aforementioned assemblage shows exceptional hemocompatibility with significant antibiofilm and antioxidant characteristics. Histological evidence of the incised skin tissue sections indicates that the fabricated composite hydrogel is also effective in controlling pro-inflammatory cytokines such as IL6 and TNFα expressions at the wound vicinity with significant upregulation of angiogenesis markers like CD31 and α-SMA.

Preparation and characterization of co-loaded indocyanine green and elemene nano-emulsion in situ gel and its effect on proliferation of breast cancer MCF-7 cells

This study aims to prepare co-loaded indocyanine green(ICG) and elemene(ELE) nano-emulsion(NE) in situ gel(ICG-ELE-NE-gel) and evaluate its physicochemical properties and antitumor activity in vitro. ICG-ELE-NE-gel was prepared by aqueous phase titration and cold solution methods, followed by characterization of the morphology, particle size, corrosion, and photothermal conversion characteristics. The human breast cancer MCF-7 cells were taken as the model, combined with 808 nm laser irradia-tion. Cell inhibition rate test and cell uptake test were performed. ICG-ELE-NE was spherical and uniform in size. The average particle size and Zeta potential were(85.61±0.35) nm and(-21.4±0.6) mV, respectively. The encapsulation efficiency and drug loading rate were 98.51%±0.39% and 10.96%±0.24%, respectively. ICG-ELE-NE-gel had a good photothermal conversion effect and good photothermal stability. The dissolution of ICG-ELE-NE-gel had both temperature and pH-responsive characteristics. Compared with free ELE, ICG-ELE-NE-gel combined with near-infrared light irradiation significantly enhanced the inhibitory effect on MCF-7 cells and could be uptaken in large amounts by MCF-7 cells. ICG-ELE-NE-gel was successfully prepared, and its antitumor activity was enhanced after 808 nm laser irradiation.

PH-responsive release of ciprofloxacin hydrochloride from micro-, nano-, and functionalized nanocellulose

This research evaluated pH-responsive release characteristics for the drug (ciprofloxacin hydrochloride) from micro-, nano-, and functionalized cellulose forms. Nanocrystalline cellulose (NCC) was prepared from microcrystalline cellulose (MCC) by sulfuric acid hydrolysis. The aldehyde (–CHO) groups were introduced at the carbon-2 (C-2) and carbon-3 (C-3) positions of glucose moiety of the cellulose network by selective oxidation to form di-aldehyde nanocellulose (DANC). The conversion was validated by chemical, spectroscopic, morphological, and crystallographic analysis. Drug binding capacity (mg/g) of DANC was higher (200.8 mg/g) compared to NCC (138.3 mg/g) and MCC (120.2 mg/g), respectively. The increase in pH from 2.5 to 8.5 enhanced drug release for all the excipients. At pH 2.5, slow release of the drugs was observed. In 6 h, DANC released 44.7 % of the loaded drug at pH 2.5. However, drug release reached equilibrium (84.8 % of loaded drug) within 10 min at pH 8.5. The release kinetics at acidic pH were validated using zero-order, first-order, Higuchi, and Korsmeyer-Peppas kinetics models. Higuchi and Korsmeyer–Peppas' kinetic models interpreted drug release phenomena with a good fit. This implies that diffusion, dissolution, swelling, and slight erosion contribute to drug release. The results suggest that selective functionalization can be applied to cellulose for its potential applications in pH-responsive drug delivery, and therefore, the functionalized cellulose deserves immediate attention.

Structural insights into the unique pH-responsive characteristics of the anti-TIGIT therapeutic antibody Ociperlimab

TIGIT is mainly expressed on Tcells and is an inhibitory checkpoint receptor that binds to its ligand PVR in the tumor microenvironment. Anti-TIGIT monoclonal antibodies (mAbs) such as Ociperlimab and Tiragolumab block the TIGIT-PVR interaction and are in clinical development. However, the molecular blockade mechanism of these mAbs remains elusive. Here, we report the crystal structures of TIGIT in complex with Ociperlimab_Fab and Tiragolumab_Fab revealing that both mAbs bind TIGIT with a large steric clash with PVR. Furthermore, several critical epitopic residues are identified. Interestingly, the binding affinity of Ociperlimab toward TIGIT increases approximately 17-fold when lowering the pH from 7.4 to 6.0. Our structure shows a strong electrostatic interaction between ASP103HCDR3 and HIS76TIGIT explaining the pH-responsive mechanism of Ociperlimab. In contrast, Tiragolumab does not show an acidic pH-dependent binding enhancement. Our results provide valuable information that could help to improve the efficacy of therapeutic antibodies for cancer treatment.

Development and performance evaluation of self-assembled pH-responsive curcumin-bacterial exopolysaccharide micellar conjugates as bioactive delivery system

The present study reports the synthesis of micellar conjugates, wherein curcumin (Cur), a bioactive compound with poor bioavailability, was covalently bonded to a bacterial exopolysaccharide (EPS). These conjugates were synthesized by utilizing succinic acid that linked Cur to the pyranosyl moiety of the EPS. The Cur-EPS conjugates appeared as spherical micelles in aqueous solution and were found to have an average hydrodynamic diameter of 254 ± 2.7 nm. The micellar conjugates showed superior stability than Cur as evident from their negative surface charge (−27 ± 1.8 mV) and low polydispersity index (PDI) (0.33 ± 0.04). The in vitro studies on release kinetics helped elucidate the pH-responsive characteristics of the Cur-EPS conjugate, as 87.50 ± 1.45 % of Cur was released at an acidic pH of 5.6, in contrast to 30.15 ± 2.61 % at systemic pH of 7.4 at 150 h. The conjugates were hemocompatible and exhibited cytotoxic effect against the osteosarcoma cell line (MG-63) after 48 h treatment. They also demonstrated superior antibacterial, antibiofilm, and antioxidant activities in comparison to free Cur. Therefore, the Cur-EPS conjugates have potential pharmaceutical applications as therapeutic biomaterial that can be applied as a drug delivery system.

Fabrication, characterization and release behavior of α-tocopherol acetate-loaded pH-responsive polyhydroxybutyrate/cellulose acetate phthalate microbeads

Microbeads are used in personal care and cosmetic products (PCCPs) but are produced from nondegradable materials. Biodegradable polyhydroxybutyrate (PHB) has been recognized as a promising alternative material for use in PCCPs; however, utilizing PHB to encapsulate PCCPs is challenging because PCCPs need to be protected from the environment but their release needs to be permitted under specific physiological conditions. The aim of this work was to develop and evaluate pH-responsive cellulose acetate phthalate (CAP) to formulate lipophilic α-tocopherol acetate (α-TA)-loaded pH-responsive PHB/CAP microbeads. The influences of the PHB/CAP ratio and initial α-TA loading on the microbead size, surface morphology, encapsulation efficiency (%EE), loading capacity (%LC), and α-TA release profile were studied. The microbeads exhibited a spherical shape with a size of 328.7 ± 2.9 μm. The EE and LC were 86.7 ± 2.6 % and 13.5 ± 0.4 %, respectively. The release profile exhibited pH-responsive characteristics. These α-TA-loaded pH-responsive microbeads were stable with >50 % of the α-TA remaining after 90 days at 4, 25 and 45 °C in the dark. The results from the cytotoxicity assay with PSVK1 cells demonstrated that the microbeads were nontoxic. Hence, our developed formulation has the potential to be used to encapsulate oil-based drugs to formulate lipophilic substance-loaded pH-responsive microbeads.

Dual responsive curcumin loaded N-isopropylacrylamide/acrylated linseed oil copolymeric hydrogel films: tuned LCST with value-added properties

Biocompatible curcumin incorporated AELO-co-PNIPAm copolymeric hydrogels developed with fine tuned LCST, antioxidant and pH responsive features.

Plectin-1-targeted recognition for enhancing comprehensive therapy in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) poses a formidable challenge due to its aggressive nature and poor prognosis. Gemcitabine (Gem), a primary therapeutic option, functions by inhibiting DNA synthesis and promoting apoptosis, thereby impeding the progression of PDAC. However, Gem is hindered by suboptimal pharmacokinetics and efficacy. In response to these challenges, we have developed a nanoparticle (NP) designed for specific recognition of plectin-1 in PDAC cell membranes. The NPs encapsulate Gem while demonstrating pH-responsive drug release characteristics in the acidic tumor microenvironment. This targeted approach enhances local drug delivery while alleviating concerns about systemic toxicity. Furthermore, the NPs are enriched with indocyanine green (ICG), renowned for its strong photothermal effects, thereby further enhancing therapeutic outcomes. This study presents an innovative therapeutic strategy for PDAC based on a plectin-1-targeted recognition delivery approach. The approach is applied to enhance chemotherapy, combined with photothermal therapy (PTT), inducing apoptosis in PDAC cell lines and improving the pharmacokinetics of Gem. In conclusion, the delivery strategy based on plectin-1-targeted recognition shows promising preclinical prospects for enhancing therapeutic efficacy in PDAC, offering valuable insights for future clinical applications.

Collagen/functionalized cellulose nanofibril composite aerogels with pH-responsive characteristics for drug delivery system

In this work, carboxylated and amination modified cellulose nanofibrils (CNFs) were fabricated via the TEMPO catalytic oxidation system and diethylenetriamine, and collagen composite aerogels were fabricated through a simple self-assembly pretreatment and directional freeze-drying technology. Morphology analysis showed that the collagen composite aerogels had distinct layered-oriented double network structures after the self-assembly pretreatment. The intermolecular interactions between the collagen fibrils and functionalized CNFs (fCNFs) on the structures and properties of the composite aerogels were also examined through various characterization techniques. Water contact angle tests demonstrated the pH-responsive characteristics of the collagen/fCNF composite aerogels. Using 5-fluorouracil as the model drug, the pH-response mechanism was revealed. These results indicated that the collagen/fCNF composite aerogels exhibited excellent pH-responsive drug release capacities. Therefore, these pH-responsive collagen composite aerogels might have potential applications in industrial production in the biomedical, drug delivery, and tissue engineering fields.

Polyaniline Microspheres with Corrosion Inhibition, Corrosion Sensing, and Photothermal Self-Healing Properties toward Intelligent Coating.

A smart coating integrating functions of corrosion inhibition, self-healing, and corrosion-sensing was developed based on a polyaniline (PANI) microsphere-loading corrosion sensing probe (8-hydroxyquinone, 8-HQ). The PANI microsphere was prepared in a facile one-pot process via the combination of photopolymerization and an emulsion template. The 8-HQ-loaded PANI microsphere achieved three synergetic effects simultaneously: corrosion inhibition, corrosion sensing, and photothermal self-healing abilities. Benefiting from the corrosion inhibition effect of PANI, the coating with the PANI microsphere exhibited significantly enhanced anticorrosion behavior. After soaking in NaCl solution for 35 days, its impedance was maintained at 1.26 × 109 Ω·cm2, nearly 3 orders of magnitude higher than that of pure resin coating. Meanwhile, the encapsulated 8-HQ exhibited pH-responsive release behavior thanks to the pH-responsive characteristics of PANI, which could chelate with Al3+ ions to form 8-HQ-Al3+ coordinates with a conspicuous fluorescence, achieving a real-time corrosion diagnosing function. Moreover, benefiting from the photothermal property of PANI, the coating with the PANI microsphere displayed rapid crack closure behavior under NIR light irradiation, and the healing efficiency could reach 83.56% under near-infrared irradiation. This work presents an innovative strategy for fabricating an intelligent self-healing, self-reporting, and anticorrosion coating, which provides a new vision to prolong the lifetime of metals.

Probing the pH Sensitivity of OprM: Insights into Metastable States and Semi-Open Conformation.

Efflux pumps are specialized transport proteins that play a key role in the bacterial defense against a wide spectrum of antibiotics. Hence, understanding the biophysical mechanism associated with this complex system of drug expulsion becomes crucial. This work deals with some vital aspects of the outer membrane factor (OMF) of MexAB-OprM. After being passed through MexB and MexA, efflux substrates have to go through OprM for their final judgment. Thus, it is very important to understand the periplasmic pore opening mechanism and the associated biophysical changes during this process. Our study captures a detailed analysis of the pore opening mechanism involving OprM. With powerful molecular dynamics (MD) techniques such as well-tempered metadynamics, the presence of metastable states in between open and closed states was confirmed. Also, upon mutating R376, the energy barrier for the conversion of the close to open conformation decreases, indicating an important role played by the residue. Further, constant pH MD was performed to capture the effect of pH in both conformations. OprM exhibits distinct conformational states at pH values greater than 5.5 and lower than 5.5, suggesting its pH-responsive characteristics. Overall, our study elucidates a crucial undertaking toward discovering potential inhibitors for MexAB-OprM efflux pumps.

A versatile polyphenol-coordinated eco-friendly hollow ZIF-based nanohybrid for precise fungicide delivery and highly efficient suppression of Botrytis cinerea

Considerable attention has been focused on the development of smart and environmentally friendly nano-pesticides that can respond to environmental stimuli, to enhance pesticide utilization while mitigating environmental risks. In this study, boscalid (Bos), a potent fungicide, was loaded into hollow zeolitic imidazolate framework-8 nanoparticles (HZNs) and coordinated with tannic acid (TA) to fabricate a pH-responsive nanohybrid platform (Bos@HZNs@TA). Results demonstrated that the HZNs@TA carriers possessed a distinct rhombic dodecahedral morphology and enhanced hydrophilic properties. The loading capacity of Bos in HZNs@TA was approximately 38.43%. Bos@HZNs@TA exhibited excellent adhesion to tomato leaves and washout resistance. Notably, the release amount of Bos from Bos@HZNs@TA at pH = 5.5 reached 84.6%, which was higher than that at neutral pH conditions for 72 h. The pH-responsive release characteristics of Bos@HZNs@TA was advantageous for its response to the acidic microenvironment created by Botrytis cinerea (B. cinerea). Additionally, Bos@HZNs@TA demonstrated exceptional effectiveness in controlling B. cinerea, surpassing the commercial Bos suspension concentrate. Importantly, Bos@HZNs@TA had no discernible adverse effects on the three non-target organisms, implying a good biocompatibility. This study provides a smart, eco-friendly, and sustainable approach to control B. cinerea effectively for plant protection.

Photoreactive silver-containing supramolecular polymers that form self-assembled nanogels for efficient antibacterial treatment

In this study, an efficient synthetic strategy and potential route to obtain a photo-reactive silver-containing cytosine-functionalized polypropylene glycol polymer (Ag-Cy-PPG) was developed by combining a hydrophilic oligomeric polypropylene glycol (PPG) backbone with dual pH-sensitive/photo-reactive cytosine-silver-cytosine (Cy-Ag-Cy) linkages. The resulting photo-responsive Ag-Cy-PPG holds great promise as a multifunctional biomedical material that generates spherical-like nanogels in water; the nanogels exhibit high antibacterial activity and thus may significantly enhance the efficacy of antibacterial treatment. Due to the formation of photo-dimerized Cy-Ag-Cy cross-linkages after UV irradiation, Ag-Cy-PPG converts into water-soluble cross-linked nanogels that possess a series of interesting chemical and physical properties, such as intense and stable fluorescence behavior, highly sensitive pH-responsive characteristics, on/off switchable phase transition behavior, and well-controlled release of silver ions (Ag+) in mildly acidic aqueous solution. Importantly, antibacterial tests clearly demonstrated that irradiated Ag-Cy-PPG nanogels exhibited strong antibacterial activity at low doses (MIC values of < 50 μg/mL) against gram-positive and gram-negative bacterial pathogens, whereas non-irradiated Ag-Cy-PPG nanogels did not inhibit the viability of bacterial pathogens. These results indicate that irradiated Ag-Cy-PPG nanogels undergo a highly sensitive structural change in the bacterial microenvironment due to their relatively unstable π-conjugated structures (compared to non-irradiated nanogels); this change results in a rapid structural response that promotes intracellular release of Ag+ and induces potent antibacterial ability. Overall, this newly created metallo-supramolecular system may potentially provide an efficient route to dramatically enhance the therapeutic effectiveness of antibacterial treatments.

Novel Hydrolytic Degradable Crosslinked Interpenetrating Polymeric Networks (IPNs): An Efficient Hybrid System to Manage the Controlled Release and Degradation of Misoprostol.

The goal of this study was to make pH-sensitive HPMC/Neocel C19-based interpenetrating polymeric networks (IPNs) that could be used to treat different diseases. An assembled novel carrier system was demonstrated in this study to achieve multiple functions such as drug protection and self-regulated release. Misoprostol (MPT) was incorporated as a model drug in hydroxyl-propyl-methylcellulose (HPMC)- and Neocel C19-based IPNs for controlled release. HPMC- and Neocel C19-based IPNs were fabricated through an aqueous polymerization method by utilizing the polymers HPMC and Neocel C19, the initiator ammonium peroxodisulfate (APS), the crosslinker methylenebisacrylamide (MBA), and the monomer methacrylic acid (MAA). An IPN based on these materials was created using an aqueous polymerization technique. Samples of IPN were analyzed using scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), thermal analysis (TGA), and powder X-ray diffraction (PXRD). The effects of the pH levels 1.2 and 7.4 on these polymeric networks were also studied in vitro and through swelling experiments. We also performed in vivo studies on rabbits using commercial tablets and hydrogels. The thermal stability measured using TGA and DSC for the revised formulation was higher than that of the individual components. Crystallinity was low and amorphousness was high in the polymeric networks, as revealed using powder X-ray diffraction (PXRD). The results from the SEM analysis demonstrated that the surface of the polymeric networks is uneven and porous. Better swelling and in vitro results were achieved at a high pH (7.4), which endorses the pH-responsive characteristics of IPN. Drug release was also increased in 7.4 pH (80% in hours). The pharmacokinetic properties of the drugs showed improvement in our work with hydrogel. The tablet MRT was 13.17 h, which was decreased in the hydrogels, and its AUC was increased from 314.41 ng h/mL to 400.50 ng h/mL in hydrogels. The blood compatibility of the IPN hydrogel was measured using different weights (100 mg, 200 mg, 400 mg, and 600 mg; 5.34%, 12.51%, 20.23%, and 29.37%, respectively). As a result, IPN composed of HPMC and Neocel C19 was successfully synthesized, and it is now possible to use it for the controlled release of MPT.

A self-degradable “nanoarmor” coating of medical implant potentiates bone fracture healing

Bionic functional coating plays a pivotal role in promoting internal fixation treatment of bone fracture. However, post-traumatic microenvironment characterized by hypoxia and acidic milieu, as well as high oxidative stress, may largely weaken the function of established coatings. Herein, we anchor two-dimensional H-silicene nanosheet (H-Si) onto hydroxyapatite (HA)-coated metal implant to develop a H-Si@HA composite coating. Benefiting from the intrinsic pH-responsive characteristics, the H-Si@HA maintains stable structure and functionalities in acidic milieu and simulates the superoxide dismutase and peroxidase-like activities, resulting in reactive oxygen species depletion, high oxidative stress suppression and further reversal of the acidic microenvironment. Meanwhile, H-Si@HA protects cells by inducing cellular autophagy. Sequentially, Si4+ release accompanying the degradation of the H-Si in neutral milieu promotes fracture healing by improving osteogenic-related gene expression of bone mesenchymal stem cells (BMSCs) and SOD1 expression of osteoprogenitor cells. Particularly, differentiated gene expression of BMSCs by the H-Si@HA coating was identified using absolute quantitative transcriptome sequencing, revealing that the H-Si could effectively modulate the expression of core mRNAs which are highly associated with osteogenesis and bone formation through regulating autophagy. Such a self-degradable nanoarmor coating illustrates the great clinic potential to achieve hierarchical and synergistic effect of fracture healing promotion.