pH-responsive Properties Research Articles

Biomimetic AgNPs@antimicrobial peptide/silk fibroin coating for infection-trigger antibacterial capability and enhanced osseointegration.

Endowing implant surfaces with combined antibacterial and osteogenic properties by drug-loaded coatings has made great strides, but how to achieve the combined excellence of infection-triggered bactericidal and in vivo-proven osteogenic activities without causing bacterial resistance still remains a formidable challenge. Herein, antimicrobial peptides (AMPs) with osteogenic fragments were designed and complexed on the surface of silver nanoparticle (AgNP) through hydrogen bonding, and the collagen structure-bionic silk fibroin (SF) was applied to carry AgNPs@ AMPs to achieve infection-triggered antibacterial and osteointegration. As verified by TEM, AMPs contributed to the dispersion and size-regulation of AgNPs, with a particle size of about 20 nm, and a clear protein corona structure was observed on the particle surface. The release curve of silver ion displayed that the SF-based coating owned sensitive pH-responsive properties. In the antibacterial test against S.aureus for up to 21 days, the antibacterial rate had always remained above 99%. Meanwhile, the underlying mechanism was revealed, originating from the destruction of the bacterial cell membranes and ROS generation. The SF-based coating was conducive to the adhesion, diffusion, and proliferation of bone marrow stem cells (BMSCs) on the surface, and promoted the expression of osteogenic genes and collagen secretion. The in vivo implantation results showed that compared with the untreated Ti implants, SF-based coating enhanced osseointegration at week 4 and 8. Overall, the AgNPs@AMPs-loaded SF-based coating presented the ability to synergistically inhibit bacteria and promote osseointegration, possessing tremendous potential application prospects in bone defects and related-infection treatments.

Synthesis and characterization of carboxymethyl chitosan/epoxidized soybean oil based conjugate catalyed by UV light, and its application as drug carrier for fusarium wilt

In this paper, a cationic photoinitiator (TAS) was used as a catalyst for the ring opening reaction of carboxymethyl chitosan (CMCS) and epoxidized soybean oil (ESO) under UV light to prepare CMCS-g-ESO conjugate, and the structure of the product was characterized by FT-IR, 1H NMR and GPC. Then, the spinosad-loaded microcapsules (SSD@CMCS-g-ESO) were prepared by ultrasonic self-assembly method. The results showed that TAS could catalyze the ring opening reaction of CMCS and ESO under UV-irradiation and the optimum reaction time was 1 h, with the molecular weight of 15,745. The average particle size of SSD@CMCS-g-ESO was about 2.16 μm, and the encapsulation efficiency (EE) and drug loading content (LC) of SSD@CMCS-g-ESO were 85.39 ± 2.05% and 20.17 ± 1.84%, respectively. In vitro release revealed that SSD@CMCS-g-ESO exhibited sustained-release and pH-responsive property, and the accumulative release in the buffer solution of pH = 6.5 and 7.4 was higher than in pH = 9.0. Furthermore, SSD@CMCS-g-ESO had a good antifungal properties against Fusarium oxysporum f. sp. cubense (Foc) compared with the unencapsulated SSD at the same drug dose. This work indicated that photo-chemical reactions could be used to prepare bio-based carrier materials to construct drugs delivery system for targeted treatment of fusarium wilt.

PH-responsive phototherapeutic poly(acrylic acid)-calcium phosphate passivated TiO2 nanoparticle-based drug delivery system for cancer treatment applications

This paper reports the hydrothermal synthesis and characterization of poly(acrylic acid)-calcium phosphate passivated TiO2 nanoparticles (TiO2@PAA-CaP NPs). The efficient loading and release of doxorubicin (DOX) from the TiO2@PAA-CaP NPs was observed at pH = 7.4 and 5.2, respectively. The loading and encapsulation amount of DOX in TiO2@PAA-CaP NPs was approximately fifteen and eight times as large as that of unfunctionalized TiO2 NPs, respectively, suggesting the PAA-CaP passivation layer enhanced the interaction between DOX and TiO2@PAA-CaP NPs. The DOX-loaded TiO2@PAA-CaP (TiO2@PAA-CaP(DOX)) NPs exhibited much faster cumulative DOX release at acidic pH = 5.2 than at neutral pH = 7.4 because of the pH-responsive dissolution properties of the PAA-CaP passivation layer. TiO2@PAA-CaP(DOX) NPs showed higher cytotoxicity towards MCF-7 tumor cells than free DOX. Confocal fluorescence microscopy and flow cytometry confirmed the enhanced cellular uptake of TiO2@PAA-CaP(DOX) NPs followed by the intracellular release of DOX. Overall, TiO2@PAA-CaP(DOX) NPs demonstrated significantly higher total cytotoxicity towards MCF-7 tumor cells under UV-A irradiation, which was attributed to a synergistic effect between efficient DOX delivery and enhanced photoinduced reactive oxygen species (ROS) generation. This study provides a facile means of synthesizing TiO2-based multifunctional nanocarriers with pH-responsive drug delivery and ROS generation essential for high efficacy therapeutic applications in cancer treatments.

Fabrication of a multifunctional nanomaterial from a mussel-derived peptide for multimodal synergistic cancer therapy

Development of biocompatible and cell-targeting nanomaterials with multimodal therapeutic approach is important to cancer treatment by overcoming its multidrug resistance. Herein, we designed and synthesized a novel multimodal therapeutic nanomaterial from a mussel-derived peptide with good biocompatibility, cell-targeting ability, and self-assembling property. Relying on Fe(III)-catechol coordination and other noncovalent interactions, the mussel-derived peptide can self-assemble to form Fe(III)-DA complexes with intrinsic photothermal and chemodynamic activities in its nanoparticle. Because of the pH-responsive property, the nanoparticle disassembled to release doxorubicin (DOX) and ferric ions under acidic intracellular environment, inducing cellular apoptosis and elevating the cellular oxidative level (ROS) via iron-mediated Fenton reactions. Besides photothermal ablation, the heat generated by Fe(III)-DA complexes from NIR irradiation could increase the DOX-induced antitumor activity, and enhance the efficiency of the Fenton reaction for chemodynamic therapy, realizing synergistic treatment of cancer cells with minimal side effects.

Green Synthesis of De Novo Bioinspired Porous Iron-Tannate Microstructures with Amphoteric Surface Properties

Bioinspired porous microstructures of iron-tannate (Fe(III)-TA) coordination polymer framework were synthesized by catenating natural tannic acid with iron(II), using a scalable aqueous synthesis method in ambient conditions. The chemical composition, morphology, physiochemical properties, and colloidal stability of microstructures were elucidated. The surface area (SBET) and the desorption pore volume were measured to be 70.47 m2/g and 0. 44 cm3/g, respectively, and the porous structure was confirmed with an average pore dimension of ~27 nm. Microstructures were thermally stable up to 180 °C, with an initial weight loss of 13.7% at 180 °C. They exhibited high chemical stability with pH-responsive amphoteric properties in aqueous media at pH levels ranging from 2 to 12. Supporting their amphoteric sorption, microstructures exhibited rapid removal of Pb+2 from water, with 99% removal efficiency, yielding a maximum sorption capacity of 166.66 mg/g. Amphoteric microstructures of bioinspired metal–phenolate coordination polymers remain largely unexplored. Additionally, natural polyphenols have seldomly been used as polytopic linkers to construct both porous and pH-responsive amphoteric coordination polymer frameworks with a robust structure in both acidic and basic media. Thus, this de novo porous microstructure of Fe(III)-TA and its physiochemical surface properties have opened new avenues to design thermally and chemically stable, eco-friendly, low-cost amphoteric sorbents with multifunctionality for adsorption, ion exchange, separation, storage, and sensing of both anions and cations present in heterogeneous media.

Design and fabrication of chitosan-based AIE active micelles for bioimaging and intelligent delivery of paclitaxel

In this study, cetyl 4-formylbenzoate alkyl and 4-(2-hydroxyethoxy) benzophenonesalicylaldazide modified biotinylated chitosan (CS-BT-HBS-CB) featured with aggregation-induced emission (AIE) characteristic, active tumor-targeting ability and pH-responsive drug release property was designed and synthesized. The polymer was fabricated by introducing hydrophobic segment, tumor targeting ligand, acid-sensitive bond and AIE fluorophore to the backbone of chitosan. Due to its amphiphilicity, the polymer could self-assemble into micelles and encapsulate paclitaxel (PTX) to form PTX-loaded CS-BT-HBS-CB micelles. The mean size of the micelles was 167 nm, which was beneficial to the EPR effect. Moreover, with the help of above functional groups, the micelles exhibited excellent AIE effect, triggered drug release behavior by acidic condition, selective internalization by MCF-7 cells and excellent cellular imaging capability. In vivo studies revealed that the PTX-loaded CS-BT-HBS-CB micelles could enhance the antitumor efficacy with low systemic toxicity. This micellar system would be a potential candidate for cancer therapy and bioimaging.

Characterization and Equilibrium Study of Drug Release of pH-Responsive Chitosan-graft-Maleic Film

This paper reports on a pH responsive material and a mathematical model for a drug release study. This material can be applied as a tumor drug carrier, because the tumor tissue has a different pH (5.7–7.8) compared to the healthy tissue (7.3–7.4). Maleic anhydride (MA) is introduced into the chitosan (CTS) backbone to create a polyampholyte chitosan-graft-maleic (CgM) film that has a pH responsive property. The success of the reaction is confirmed by Fourier transform infrared spectroscopy, which shows a new peak at 1705cm-1

Smart waterborne composite coating with passive/active protective performances using nanocontainers based on metal organic frameworks derived layered double hydroxides

Functional surfaces and coatings with excellent anticorrosion performances are of great significance for numerous engineering applications. However, developing waterborne coatings with long-term anticorrosion properties remains challenging. In this study, we developed a multifunctional nanocontainer for a waterborne coating matrix, using zeolitic imidazolate framework (ZIF)-derived layered double hydroxides (LDHs) as the gatekeepers for benzotriazole (BTA)-encapsulated mesoporous silica nanoparticles (MSNs-BTA). The LDHs outer layer and the ZIF intermediate layer endowed the MSNs-BTA@ZIF-LDHs nanocontainer with excellent compatibility, dispersion, and pH-responsive controllable release properties in the waterborne coating matrix. The waterborne epoxy composite coatings showed excellent passive and active anticorrosion performances, well-characterized by electrochemical impedance spectroscopy (EIS), permeation experiments, neutral salt spray (NSS) tests, and the scanning vibrating electrode technique (SVET). This excellent corrosion protection performance can be attributed to two factors: before corrosion, the MSNs-BTA@ZIF-LDHs served as passive nanofillers against corrosive media, significantly improving the barrier properties of the composite coatings; after the occurrence of corrosion, the MSNs-BTA@ZIF-LDHs acted as pH-responsive nanocontainers and released pre-loaded BTA corrosion inhibitors, preventing further damage to the exposed metal substrate. This study provides new insights into the development of multifunctional anticorrosion surfaces and coatings for various engineering applications.

Tunning the properties of pH-responsive lignin-based hydrogels by regulating hydroxyl content

Although pH-sensitive lignin-based materials have extensively attracted attentions because of the smart response to pH, it is still a challenge to realize the regulation of the pH-responsive properties. Focusing on this problem, we proposed a new method by tunning the content of hydroxyl groups to adjust the performances of lignin-based hydrogel (L-HG). The modified lignins with the hydroxyl content ranged from 0.31 to 5.91 mmol/g were obtained after acetylation or demethylation. As the results, when increasing the hydroxyl content, the gels became more compact and smooth, and the tensile strength reached 4.10 MPa. The strain was up to 83.2%, and the bending behavior occurred more easily at various pH (3, 5, 9, 11 and 13). While decreasing the hydroxyl content resulted in the impairments of almost all of the above performances. Based on the test of the moisture content, the pH-sensitive bending behavior might be mainly caused by the opposing forces of hydrophilic and hydrophobic interaction. Finally, the application test showed that the trimmed hydrogel could hook up 10 times weight greater than itself under both acid and alkaline conditions. We believe that this work would provide the theoretical guidance for the regulation of pH sensitivity of L-HG.

Progress in the Development of Graphene-Based Biomaterials for Tissue Engineering and Regeneration.

Over the last few decades, tissue engineering has become an important technology for repairing and rebuilding damaged tissues and organs. The scaffold plays an important role and has become a hot pot in the field of tissue engineering. It has sufficient mechanical and biochemical properties and simulates the structure and function of natural tissue to promote the growth of cells inward. Therefore, graphene-based nanomaterials (GBNs), such as graphene and graphene oxide (GO), have attracted wide attention in the field of biomedical tissue engineering because of their unique structure, large specific surface area, good photo-thermal effect, pH response and broad-spectrum antibacterial properties. In this review, the structure and properties of typical GBNs are summarized, the progress made in the development of GBNs in soft tissue engineering (including skin, muscle, nerve and blood vessel) are highlighted, the challenges and prospects of the application of GBNs in soft tissue engineering have prospected.

Carbon dots enhanced gelatin/chitosan bio-nanocomposite packaging film for perishable foods

Carbon dots (CDs) with intriguing fluorescent property, good biocompatibility, high stability, easy interaction with substrates, are burgeoning carbon nanoparticles with large potential in various applications. Incorporating CDs into the polymer matrix is becoming a popular strategy to endow the complex with new functions. Herein, the green-synthesized CDs was integrated into the mixture of gelatin (derived from waste fish scale) and chitosan, and a multifunctional bio-nanocomposite (defined as Gelatin/Chitosan/CDs) film was developed, which showed the excellent antibacterial, antioxidant, pH-sensitivity, UV shielding, and blue-emission properties. The effects of different concentrations of CDs on the physical, mechanical, structural, and functional activity of bio-nanocomposite film were tested. Compared with the Gelatin/Chitosan film, the Gelatin/Chitosan/CDs film with an optimum addition of 20% CDs showed the enhanced antibacterial, antioxidant as well as UV shielding activities. More importantly, it was used as an effective packaging material for fish meat preservation, reducing the loss of nutritional quality consumption, extending the shelf life of food. Besides, the bio-nanocomposite films also possessed the anti-counterfeiting and pH-responsive properties due to the strong fluorescent emission of CDs, and had the great potential in developing the intelligent packaging materials. Our work shed new light on the new application of CDs and the synthesis of bio-nanocomposite film in food industry.

Metal-Organic Framework-Based Nanotherapeutics With Tumor Hypoxia-Relieving Ability for Synergistic Sonodynamic/Chemo-therapy

Hypoxia, a hallmark of cancer, compromises the efficacy of chemotherapy and other oxygen-dependent modalities (e.g., sonodynamic therapy). For monotherapy, this effect becomes more pronounced because of drug resistance and an adaptive tumor microenvironment. To overcome this, here, we reported metal–organic framework (MOF)-based nanotherapeutics (DOX/Ce6@ZIF-8@PDA) to simultaneously deliver Ce6 and doxorubicin for synergistic sonodynamic/chemotherapy. Notably, O2 storage ability of MOFs relieves tumor hypoxia to sensitize the tumor to sonodynamic therapy and chemotherapy. Moreover, polydopamine (PDA) promotes endocytosis and enhances intracellular drug concentration. The pH-responsive property of MOFs enables controlled drug release. The in vitro and in vivo results validate the impressive tumor inhibition, implying the potential of this combination therapy for cancer treatment.

Reusable poly(2-acrylamido-2-methylpropanesulfonic acid)-grafted magnetic nanoparticles as anionic nano-adsorbents for antibody and antigen

Magnetite nanoparticles (MNPs) grafted with poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) and their use as anionic nano-adsorbents for positively charged antibody were herein presented. PAMPS grafted on MNP surface provided good water dispersibility and high negatively charged surface for electrostatic adsorption with positively charged entities, and MNPs provided a good magnetic responsiveness to facilitate the separation process. From transmission electron microscopy results, the size of the nanoclusters ranged between 50 and 200 nm in diameter with ca. 50–150 particles/cluster. Degree of the negative charge of PAMPS-grafted MNPs increased when increasing pH of the dispersion, indicating the pH-responsive properties of the MNPs. These MNPs were successfully used as nano-adsorbents for adsorption with anti-rabbit IgG through ionic interaction between negative charge of PAMPS-grafted MNP and positive charge of the antibody. In addition, the MNPs also provided the reusable ability by adsorption-desorption cycling process with higher than 80% adsorption ability after five consecutive reusing cycles. These hybrid materials should be alternative nano-adsorbents for other positively charged entities with high adsorption efficiency and reusable supports in magnetic separation applications.

All-In-One Biomimetic Nanoplatform Based on Hollow Polydopamine Nanoparticles for Synergistically Enhanced Radiotherapy of Colon Cancer.

Even though radiotherapy is the most important therapeutic strategy for colon cancer treatment, there is an enormous demand to improve radiosensitivity in solid tumor destruction. For this purpose, a biomimetic nanoplatform based on hollow polydopamine nanoparticles (HP) with homologous targeting and pH-responsive drug release properties is designed. In this work, HP is constructed by using a chelation competition-induced polymerization strategy and then modified with the cancer cell membrane. Hollow polydopamine integrated with Pt nanoparticles (Pt@HP) has a catalase-like activity, which can be used to trigger endogenous H2 O2 into O2 , relieving hypoxia of the tumor microenvironment (TME). With mesoporous shells and large cavities, Pt@HP shows efficient apoptin100-109 (AP) and verteporfin (VP) loading to form AVPt@HP@M. Under X-ray irradiation, AVPt@HP@M exerts a radiosensitization effect via multiple strategies, including relieving hypoxia (Pt NPs), enhancing tumor apoptosis (AP), and X-ray-induced photodynamic therapy (X-PDT) (VP). Further metabonomics analysis shows that the specific mechanism of the AVPt@HP@M is through influencing purine metabolism. Without appreciable systemic toxicity, this nanoplatform highlights a new strategy for effective radiosensitization and provides a reference for treating malignant tumors.

Covalent organic framework-based fluorescent nanoprobe for intracellular pH sensing and imaging

Lysosomes are the acidic organelles in the cells that play an important role in intracellular degradation and other various cellular functions. The pH disturbance of lysosomes will result in the lysosomal dysfunction and many lysosomal related diseases. In this work, we reported a methoxy-based covalent organic framework (TAPB-DMTP-COF) that a novel pH-responsive fluorescent probe for lysosomal pH imaging in cells. The prepared TAPB-DMTP-COF presented regular crystal structure, low toxicity and good pH responsive property. The rich imine structure in the material enabled pH-responsive properties of the TAPB-DMTP-COF and made it exhibited pH-dependent fluorescence response. Good detection linearity for pH measurements in aqueous solution was achieved by this probe. Moreover, the TAPB-DMTP-COF can be used for the selective lysosomal pH imaging. Confocal fluorescence imaging results demonstrated that the pH fluctuations (from 4.0 to 7.4) and the pH changes in lysosomes can be effectively monitored in situ by the developed probe. This study may provide a new avenue for the intracellular pH sensing, deep study and understanding about the mechanism of diseases related to abnormal lysosomal pH.

Solution properties of amphiphilic amino- and oligoethylene glycol-containing methacrylic copolymers

The behavior of methacrylic copolymers with oligoethylene glycol and amine groups in aqueous solutions has been studied. The eff ect of the composition of copolymers of alkoxyoligo(ethylene glycol) methacrylates and N-[3-(dimethylamino) propyl] methacrylamide on their solubility in aqueous media, aggregation properties and surface activity at the water-oil phase boundary was demonstrated. The presence of thermo- and pH-responsive properties, characterized by lower critical solution temperature, has been shown. Polymers exhibit high interfacial activity at the water-toluene interface, which increases with an increase in the proportion of methacrylic ether units in the copolymer. For polymers in aqueous media the value of the critical micelle concentration was found in the region of 10-3 g/L.

One-Step Fabrication of Hollow Spherical Cellulose Beads: Application in pH-Responsive Therapeutic Delivery.

The path to greater sustainability and the development of polymeric drug delivery systems requires innovative approaches. The adaptation and use of biobased materials for applications such as targeted therapeutic delivery is, therefore, in high demand. A crucial part of this relates to the development of porous and hollow structures that are biocompatible, pH-responsive, deliver active substances, and contribute to pain relief, wound healing, tissue regeneration, and so forth. In this study, we developed a facile single-step and water-based method for the fabrication of hollow spherical cellulose beads for targeted drug release in response to external pH stimuli. Through base-catalyzed deprotection, hydrophobic solid and spherical cellulose acetate beads are transformed into hydrophilic cellulose structures with a hollow interior (wall thickness: 150 μm and inner diameter: 650 μm) by a stepwise increment of temperature and treatment time. Besides the pH-responsive fluid uptake properties, the hollow cellulose structures exhibit a maximum encapsulation efficiency of 20–85% diclofenac (DCF), a nonsteroidal anti-inflammatory drug, used commonly to treat pain and inflammatory diseases. The maximum amount of DCF released in vitro increased from 20 to 100% when the pH of the release medium increased from pH 1.2 to 7.4. As for the DCF release patterns and kinetic models at specific pH values, the release showed a diffusion- and swelling-controlled profile, effortlessly fine-tuned by external environmental pH stimuli. Overall, we show that the modified beads exhibit excellent characteristics for transport across the gastrointestinal tract and enhance the bioavailability of the drug. Their therapeutic efficacy and biocompatibility are also evident from the studies on human fibroblast cells. We anticipate that this platform could support and inspire the development of novel sustainable and effective polysaccharide-based delivery systems.

Red-emission carbon dots as fluorescent "on-off-on" probe for highly sensitive and selective detection of Cu2+ and glutathione.

A highly sensitive and selective fluorescent "on-off-on" strategy is established for the synchronous detection of Cu2+ and glutathione in aqueous solution. Red carbon dots (R-CDs) were prepared by using precursors of 4,5-difluoro-1,2-phenylenediamine and citric acid via a one-step hydrothermal strategy. R-CDs show a relatively long fluorescence lifetime of 3.47ns under 455nm excitation and high absolute fluorescent quantum yield of 20.1% with an excitation wavelength of 550nm. R-CDs exhibit a marked pH-responsive fluorescence property with no significant perturbation from pH 4 to pH 13 even after five cycles. R-CDs with higher concentration of 750μg·mL-1 exhibit no significant cytotoxicity and good biocompatibility on HeLa cells and A549 cells after incubation for 48h. The fluorescence of R-CDs at 619nm (excited at 550nm) is quenched statically by Cu2+ and recovered by glutathione subsequently, resulting in a fluorescent "on-off-on" assay for the synchronous detection of Cu2+ and glutathione. Under optimal conditions, the linear response covers the Cu2+ concentration range of 1 to 50μM and the glutathione concentration range of 1 to 70μM. Detection limits of Cu2+ and glutathione are 0.16 and 0.41μM, respectively. This fluorescent probe is applied to the determination of Cu2+ and glutathione in authentic samples with satisfying results. Such an assay broadens the potential application of CDs in environmental areas and clinical therapy fields.

Polyoxometalate-covalent organic framework hybrid materials for pH-responsive photothermal tumor therapy.

Photothermal therapy (PTT) has become one of the most effective methods for tumor treatment. With the development of medicine, studies focusing primarily on therapeutic and diagnostic agents with desirable biocompatibility, targeting and stability are still of great significance. Heteropoly blue (HPB) is an ideal photothermal therapy agent (PTA) with decent photothermal conversion efficiency. Covalent organic frameworks (COFs) are considered to be good carriers with excellent biocompatibility. Due to their superior characteristics, such as being adjustable, and having high thermal stability and porous structures, COFs have been broadly applied in various fields. In this study, HPB was successfully in situ loaded into a COF via a one-pot method. The resultant HPB@COF platform exhibited desirable biocompatibility, pH-responsive release properties and high tumor inhibition efficiency, which can be used for PTT to effectively inhibit tumor growth. Our work provides a valuable paradigm for the fabrication of safer and effective HPB@COF NPs for future pH-responsive photothermal therapy.

Preparation of a "Branch-Fruit" structure chitosan nanofiber physical hydrogels with high mechanical strength and pH-responsive controlled drug release properties.

The poor mechanical properties of chitosan physical hydrogels seriously hinder their application in the biomedical field. Inspired by the structure of cell tissues, a novel chitosan nanofiber (CSNF)/Hyaluronic acid (HA)/β-glycerophosphate disodium (β-GP) drug-loaded hydrogel was prepared by micro-dissolution and physical crosslinking. The hydrogel has a “Branch-Fruit” structure and exhibits excellent mechanical properties, good biocompatibility and cell-adhesion properties. Human cancer cells (HeLa) can adhere to the hydrogel surface, which might facilitate tumor site-specific administration of drugs. This material also exhibits high pH sensitivity, with which drug release can be triggered under acidic conditions at pH 4.00. The mechanical strength and drug release behavior of this hydrogel can be easily adjusted by varying the CSNF content.