pH-triggered Release Research Articles

PH-responsive silica nanoparticles for the treatment of skin wound infections

Chronic wounds are not only a burden for patients but also challenging for clinic treatment due to biofilm formation. Here, we utilized the phenomenon that chronic wounds possess an elevated local pH of 8.9 and developed pH-sensitive silica nanoparticles (SiNPs) to achieve a targeted drug release on alkaline wounds and optimized drug utility. Chlorhexidine (CHX), a disinfectant and antiseptic, was loaded into SiNPs as the model drug. The loaded CHX displayed a release 4 - 5 fold higher at pH 8.0 and 8.5 than at pH 6.5, 7.0 and 7.4. CHX-SiNPs furthermore exhibited a distinctive antibacterial activity at pH 8.0 and 8.5 against both Gram-negative and -positive bacterial pathogens, while no cytotoxicity was found according to cell viability analysis. The CHX-SiNPs were further formulated into alginate hydrogels to allow ease of use. The antibacterial efficacy of CHX-SiNPs was then studied with artificial wounds on ex vivo human skin. Treatment with CHX-SiNPs enabled nearly a 4-lg reduction of the viable bacterial cells, and the alginate formulated CHX-SiNPs led to almost a 3-lg reduction compared to the negative controls. The obtained results demonstrated that CHX-SiNPs are capable of efficient pH-triggered drug release, leading to high antibacterial efficacy. Moreover, CHX-SiNPs enlighten clinic potential towards the treatment of chronic wound infections. Statement of significanceA platform for controlled drug release at a relatively high pH value i.e., over 8, was established by tuning the physical structures of silica nanoparticles (SiNPs). Incorporation of chlorhexidine, an antimicrobial agent, into the fabricated SiNPs allowed a distinctive inhibition of bacterial growth at alkaline pHs, but not at acidic pHs. The efficacy of the SiNPs loaded with chlorhexidine in treating wound infections was further validated by utilizing ex vivo human skin samples. The presented work demonstrates clinic potential of employing alkaline pH as a non-invasive stimulus to achieve on-demand delivery of antimicrobials through SiNPs, showcasing a valuable approach to treating bacterial infections on chronic wounds.

Biocompatible functionalized graphene nanosheet for delivery of doxorubicin to breast cancer cells

Nanotechnology has emerged as a promising approach to overcome the obstacles against successful cancer chemotherapy. Herein, biocompatible carbon nanosheets grafted with multi-cyclodextrin were fabricated for doxorubicin delivery to breast cancer cells. Structural characteristics of the nanocarrier were evaluated by FTIR, XRD, MAP, EDS, SEM, TEM, and VSM. Drug-loading and -encapsulation efficiencies were calculated to optimize the formulation. The biocompatibility of synthesized drug-carrier was determined using hemolysis assay and the MTT assay was performed to assess the viability of MCF-7 cells after treatment with various formulations. In-vitro drug release revealed the pH-triggered drug release capability of the drug carrier which can improve the cytotoxic potency of the doxorubicin in the tumor microenvironment. Hemolysis assay indicated the blood biocompatible feature of drug carrier which is further confirmed by cytotoxicity study, while, doxorubicin-loaded drug carrier significantly enhanced the cytotoxic effect of doxorubicin. Fluorescence microscopy observations of the nucleus after DAPI staining indicated the apoptotic-inducing effect of the drug-loaded carrier in comparison to free drug. This can be due to the higher internalization rate of drug-loaded carriers observed in fluorescence microscopy images. These results suggest that the fabricated drug carrier can be considered as a possible tool for the delivery of doxorubicin to breast cancer cells.

Biomimetic and responsive nanoparticles loading JQ1 for dual-targeting treatment of vascular restenosis via multiple actions

• The biomimetic and responsive DDS had optimized JQ1 release behavior and rapid homing to injured site. • The DDS inherited natural specificity for VSMCs from platelets and obtained dual-targeting function. • Pro-inflammatory cytokines secreted from macrophages were suppressed by the DDS. • The DDS can substantially inhibit VSMCs proliferation and intima hyperplasia with little effect on VECs. Postoperative restenosis remains the key problem of coronary arterial disease and seriously threatens human health. Currently, no effective strategies can thoroughly prevent restenosis owing to its complicated progression. We hypothesize the multi-effect drug of endothelium-protective epigenetic inhibitor (JQ1) may act well in anti-restenosis via exerting multiple functions and acting on different cells. Furthermore, homing to endothelium injured site and pH-triggered drug release can enhance targeted therapeutic efficacy by JQ1 preferential accumulation at injured site and in vascular smooth muscle cells (VSMCs). To verify our hypothesis and develop targeted drug delivery system (DDS) with controlled release ability for anti-restenosis, a pH-responsive nanoparticle was prepared to encapsulate JQ1 and further camouflaged by platelet membrane (PM). The resulting biomimetic and responsive DDS showed optimized drug release behavior and rapid homing to injured site. Moreover, the internalization of DDS in VSMCs was much higher than other groups without PM, which indicated that it inherited natural specificity for VSMCs from PM and obtained dual-targeting function to enhance therapeutic efficacy. The DDS presented significant anti-inflammatory effect via inhibiting NF-κB signaling pathway and secretion of pro-inflammatory cytokines from macrophages. Besides, VSMCs proliferation was suppressed by the DDS with little effect on vascular endothelial cell proliferation and in vivo re-endothelialization at suitable JQ1 concentration. More importantly, the DDS substantially inhibited intima hyperplasia without obvious pathological variation on main organs using a mouse model of carotid artery injury. In summary, we created a versatile DDS for the promotion of JQ1 targeting delivery and responsive release at injured site to mitigate restenosis. The DDS demonstrated outstanding performance via a synergistic and comprehensive effect of multiple factors for anti-restenosis, providing a promising method for clinical applications.

Coassembling functionalized glycopolypeptides to prepare pH-responsive self-indicating nanocomplexes to manipulate self-assembly/drug delivery and visualize intracellular drug release

The pH-responsive polymeric micelles (PMs) have been widely used as smart nano drug delivery systems to treat tumors. However, synchronously manipulating these PMs' self-assembly properties, drug release dynamics and tracing their pH-dependent intracellular fate remain challenges. Herein, we have first synthesized hyaluronic acid (HA) based glycopolypeptides modified by tetraphenylethylene (TPE) and a pH-sensitive doxorubicin (DOX) prodrug through Diels-Alder reaction, respectively. Then, the pH-responsive nanocomplexes (NCs) were prepared by coassembling the two obtained glycopolypeptides with different formulations. Controllable size within the range of 60–125 nm and morphologies like spherical, vesicular and oblate micelles can be easily accomplished by using this method; High drug encapsulating and loading efficiency can be easily realized and adjusted within a range of 86–97% and 7–25%, respectively; Acid sensitive drug release dynamics of these NCs are also tunable by using this way. Additionally, the programmed drug release induced by subtle pH variations can be extracellularly self-indicated by detecting the blue AIE changes of the TPE units through fluorescence resonance energy transfer (FRET) effect between DOX and TPE. More importantly, the dynamic pH-triggered DOX release can be easily traced inside the tumor cells by visualizing blue emission changes of the TPE through the FRET effect. In addition, both the size and the shape can affect the endocytic routes of the NCs; The HA coated NCs targeting the tumor cells can effectively inhibit the proliferation of the HeLa cells. This work can provide a new route to acquire the stimuli-responsive self-indicating PMs with the ability to adjust their self-assembly properties and their pH-triggered drug release dynamics, and even to simultaneously visualize the PMs' intracellular fate in a real-time.

Doxorubicin-Loaded UiO-66/Bi2S3 Nanocomposite-Enhanced Synergistic Transarterial Chemoembolization and Photothermal Therapy against Hepatocellular Carcinoma

Transcatheter arterial chemoembolization (TACE) is the first choice for patients with intermediate hepatocellular carcinoma (HCC), but clinical applications still face some problems, such as the difficulties in clearing all cancer cells and lack of targeting, which would damage normal liver cells. Recently, photothermal therapy (PTT) and nanodelivery systems have been used to improve the efficacy of TACE. However, most of these strategies achieve only a single function, and the synthesis process is complicated. Here, a simple one-step solvothermal method was used to develop multifunctional nanoparticles (UiO-66/Bi2S3@DOX), which can simultaneously achieve photothermal effects and low pH-triggered DOX release. UiO-66/Bi2S3 exhibited a pH-responsive release behavior and an excellent photothermal effect in a series of in vitro and in vivo studies. Biocompatibility was confirmed by cytotoxicity and hemocompatibility evaluations. The rat N1S1 liver tumor model was established to investigate the therapeutic effect and biosafety of the nanoplatforms using TACE. The results revealed that the combination of TACE and PTT resulted in remarkable tumor growth inhibition, and the histopathological assay further revealed extensive necrosis, downregulated angiogenesis, increased apoptosis, and proliferation in the tumor response. These results demonstrated that this nanosystem platform was a promising therapeutic agent for enhancing TACE therapy for HCC treatment.

Pegylated dendritic polyurethane as unimolecular micelles for tumor chemotherapy: Effect of molecular architecture

Unimolecular micelles have attracted intense interests as drug carriers for tumor chemotherapy owing to their superior stability in comparison with the self-assembled supramolecular ones. Among them, the dendritic polymers with the polar frameworks could favour the loading of chemotherapeutic drugs rather than the hyperbranched polymers via radical polymerization, by enhancing the interaction with drugs. While the tedious synthesis procedure for dendritic polymers could be simplified with the construction principle on urethane chemistry. Here, the PEGylated dendritic polyurethanes, Ph-DPUGly-PEG and Ph-DPUTEA-PEG, were designed with glycerol or triethanolamine as monomer, respectively. The effect of the molecular architecture of the Ph-DPU-PEGs unimolecular micelles on the controlled drug releasing performance was compared. It was found that the Ph-DPUTEA-PEG with tertiary amine as branching points could efficiently endow the pH-triggered drug release, due to its protonation.

Nano-enabled delivery of EGCG ameliorates silica-induced pulmonary fibrosis in rats

Silicosis is the most serious occupational pulmonary fibrosis caused by excessive inhalation of silica particles, whereas viable therapeutic choices are constrained. Epigallocatechin gallate (EGCG) presents massive health benefits, but unfortunately with stability absence. Here, encapsulation of EGCG in poly(n-butylcyanoacrylate) nanoparticles (EGCG/PBCA-NPs) were fabricated by self-polymerization for gastrointestinal delivery in silicosis fibrosis treatment. The obtained nano-enabled delivery of EGCG was produced using a medical adhesive approved by FDA as carrier, and presented spherical particles with approximate diameter of 160 nm, a narrow PDI value of 0.2, Zeta potential value of 30 mV as well as a high EGCG incorporation (90 %) and loading efficiency (20 %). In evaluating the protect effects of nano-formulations, EGCG/PBCA-NPs shown excellent stability in gastric fluid with pH-triggered release in intestine and strong EGCG gastrointestinal retention against degradation. After daily gastrointestinal administration, EGCG/PBCA-NPs exhibited the superior anti-fibrosis efficacy in silicosis model rats induced by silica, involving lung index decline, hydroxyproline content decrease, histological improvement, collagen accumulation reduction and α-SMA down-regulation in comparison with naked EGCG. These results strongly demonstrated that PBCA-based NPs may be a promising nano-enabled delivery carrier for enhancing the gastrointestinal stability and anti-fibrotic effects of EGCG.

Covalent Organic Framework-Incorporated Nanofibrous Membrane as an Intelligent Platform for Wound Dressing.

Covalent organic frameworks (COFs) possess fascinating features that have sparked increasing interest as drug carriers in biomedical applications. However, the promising properties of COFs in wound healing have rarely been reported. Herein, a facile one-pot method is reported to prepare a curcumin-loaded COF (CUR@COF) by the condensation reaction and the Schiff base reaction and to further incorporate CUR@COF into polycaprolactone (PCL) nanofibrous membranes (CUR@COF/PCL NFMs) through electrospinning to develop a pH-triggered drug release platform for wound dressing. CUR@COF has a high CUR loading capacity of 27.68%, and CUR@COF/PCL NFMs exhibit increased thermal stability, improved mechanical properties, good biocompatibility, and enhanced antibacterial and antioxidant activities. More importantly, CUR@COF-based membranes show a pH-responsive CUR release profile by protonation under acidic conditions, suggesting the promotion of CUR release from membranes under an acidic extracellular microenvironment. The histopathological analysis and immunofluorescence staining of an in vivo skin defect model indicate that CUR@COF/PCL NFMs can accelerate wound healing and skin regeneration by reducing the expression of inflammatory factors (TNF-α) and enhancing the expression of angiogenesis (VEGF). This work provides a new strategy by employing COF-based drug-encapsulated nanocomposites for wound dressing applications.

Construction of calcium carbonate-liposome dual-film coated mesoporous silica as a delayed drug release system for antitumor therapy

As is well known to all, delivering drug precisely to the tumor site is beneficial to improve antitumor effect. In this study, we reported mesoporous silica nanoparticles (MSNs) coated with dual-film of calcium carbonate (CaCO3) and lipid bilayer (denoted as MSNs@CaCO3@liposomes) innovatively which achieve sustained drug release anchored at tumor microenvironment and enhanced biocompatibility. The pH-sensitive CaCO3 film acted as a guide to cap the pore channels of MSNs allowed pH-triggered drug release when transporting into cancer cells. Furthermore, MSNs@CaCO3 was capsuled by lipid bilayer to improve cellular uptake efficiency and biocompatibility in blood circulation. Morphology of nanoparticles was characterized by transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM) to confirm that double films were coated successfully. Doxorubicin hydrochloride (DOX) was efficaciously loaded into mesoporous pores as a model drug with a high drug loading content of 28%, forming DOX-loaded MSNs@CaCO3@liposomes (DOX/MSNs@CaCO3@liposomes). Non-specific protein adsorption and hemolysis test revealed enhanced biocompatibility. Drug release study in vitro showed DOX/MSNs@CaCO3@liposomes could delay to release DOX at pH 5.0 and avoid releasing at pH 7.4. In vitro and in vivo antitumor efficiency evaluation showed that DOX/MSNs@CaCO3@liposomes have a desirable inhibitory activity on tumor growth. Therefore, dual-film coated MSNs could be a good candidate for an antitumor drug delivery system.

Magnetic Biohybrid Microrobot Multimers Based on Chlorella Cells for Enhanced Targeted Drug Delivery.

Magnetic micro-/nanorobots have been regarded as a promising platform for targeted drug delivery, and tremendous strategies have been developed in recent years. However, realizing precise and efficient drug delivery in vivo still remains challenging, in which the versatile integration of good biocompatibility and reconfiguration is the main obstacle for micro-/nanorobots. Herein, we proposed a novel strategy of magnetic biohybrid microrobot multimers (BMMs) based on Chlorella (Ch.) and demonstrated their great potential for targeted drug delivery. The spherical Ch. cells around 3-5 μm were magnetized with Fe3O4 to fabricate biohybrid microrobots and then loaded with doxorubicin (DOX). Using magnetic dipolar interactions, the microrobot units could reconfigure into chain-like BMMs as tiny dimers, trimers, and so forth via attraction-induced self-assembly and disassemble reversibly via repulsion. The BMMs exhibited diverse swimming modes including rolling and tumbling with high maneuverability, and the rolling dimer's velocity could reach 107.6 μm/s (∼18 body length/s) under a 70 Gs precessing magnetic field. Furthermore, the BMMs exhibited low cell toxicity, high DOX loading capacity, and pH-triggered drug release, which were verified by chemotherapy experiments toward HeLa cancer cells. Due to the remarkable versatility and facile fabrication, the BMMs demonstrate great potential for targeted anticancer therapy.

Enhanced anti-tumor activity of a drug through pH-triggered release and dual targeting by calcium phosphate-covered mesoporous silica vehicles.

Rapid release and clearance of antitumor drugs in vivo are the main factors used to evade the effectiveness of chemotherapeutics. Targeted delivery and controlled release of drugs are the most pressing dilemmas in cancer therapy. Herein we report the design and fabrication of multifunctional mesoporous silica nanoparticles coated with poly(N-isopropylacrylamide)-co-acrylic acid and calcium phosphate (MSCNs) with pH-triggered chemotherapeutic release and dual-targeting functions. By decorating the nanoparticle surface with a transferrin (Tf)/RGD ligand, these nanoparticles are capable of not only recognizing the intrinsic pH difference between tumor and normal tissues, but also targeting the lesion location. It was shown that Tf/RGD-MSCNs delivered the anti-tumor drug doxorubicin more efficiently into lysosomes and the resulting DOX-loaded nanoparticles (DOX-Tf/RGD-MSCNs) showed a stronger inhibitory effect towards tumor cell growth than free DOX and DOX delivered by unmodified MSNs. Moreover, the nanoparticles are more biocompatible than uncoated mesoporous silica nanoparticles. All these results indicate that Tf/RGD-MSCNs have great potential as a novel drug carrier in therapeutic applications against cancers.

Development of carrier-free nanodrugs based on low molecular weight heparin–doxorubicin conjugate assembly with smart pH-triggered drug release characteristics for combinatorial antitumor therapy

A LMWH–DOX nanodrug effectively released bioactive agents, providing a combination therapy of low molecular weight heparin and doxorubicin for angiogenesis suppression and carcinoma inhibition.

MXenes in photomedicine: advances and prospects.

MXenes and their related nanocomposites with superior physicochemical properties such as high surface area, ease of synthesis and functionalization, high drug loading capacity, collective therapy potentials, pH-triggered drug release behavior, high photothermal conversion, and excellent photodynamic efficiency have been explored as alluring materials in photomedicine; the application of photons in medicine is facilitated for imaging and various disease treatment methods such as photothermal cancer/tumor ablation. Non-invasive theranostic strategies with synergistic activities have been developed using photothermal, photodynamic, and magnetic therapies together with remotely controlled drug/gene delivery for the diagnosis and treatment of various malignant diseases. Photothermal/photodynamic therapy and photoacoustic imaging using MXene-based structures have shown great promise in cancer phototherapy. However, hybridization and surface functionalization should be further explored to obtain biocompatible MXene-based composites/platforms with unique properties, high stability, and improved functionality in photomedicine. Toxicological and long-term biosafety assessments as well as clinical translation evaluations ought to be given high priority in research. Although some limited studies have revealed the excellent potentials of MXenes and their derivatives in photomedicine, further steps should be taken towards extensive research and detailed analysis in the field of optimizing the properties and improving the performance of these materials with a clinical and industrial outlook. Optical biosensing platforms have been developed along with electrochemical sensors and wearable sensors constructed from MXenes and their derivatives; future studies warrant the comprehensive analysis of optical transduction aspects such as colorimetry, electrochemiluminescence, photoluminescence, surface-enhanced Raman scattering, and surface plasmon resonance. Herein, the potentials of MXenes in photomedicine are deliberated encompassing important challenges and future research directions.

Doxorubicin delivery performance of superparamagnetic carbon multi-core shell nanoparticles: pH dependence, stability and kinetic insight

In the past decade, magnetic nanoparticles (MNPs) have been among the most attractive nanomaterials used in different fields, such as environmental and biomedical applications. The possibility of designing nanoparticles with different functionalities allows for advancing the biomedical applications of these materials. Additionally, the magnetic characteristics of the nanoparticles enable the use of magnetic fields to drive the nanoparticles to the desired sites of delivery. In this context, the development of new MNPs in new approaches for drug delivery systems (DDSs) for cancer treatment has increased. However, the synthesis of nanoparticles with high colloidal stability triggered drug delivery, and good biocompatibility remains a challenge. Herein, multi-core shell MNPs functionalized with Pluronic ® F-127 were prepared and thoroughly characterized as drug carriers for doxorubicin delivery. The functionalized nanoparticles have an average size of 17.71 ± 4.2 nm, high water colloidal stability, and superparamagnetic behavior. In addition, the nanoparticles were able to load 936 μg of DOX per mg of functionalized nanomaterial. Drug release studies at different pH values evidenced a pH-triggered DOX release effect. An increase of 62% in cumulative drug release was observed at pH simulating tumor endosome/lysosome microenvironments (pH 4.5) compared to physiological conditions (pH 7.4). In addition, an innovative dynamic drug delivery study was performed as a function of pH. The results from this test confirmed the pH-induced doxorubicin release capability of carbon multi-core shell MNPs. The validity of traditional kinetic models to fit dynamic pH-dependent drug release was also studied for predictive purposes.

Venturi-based rapid expansion of supercritical solution (Vent-RESS): synthesis of liposomes for pH-triggered delivery of hydrophilic and lipophilic bioactives.

Multivitamin-loaded and surface-modified liposomes tailored for simultaneous intestinal delivery of both lipophilic and hydrophilic bioactives were synthesized from sunflower phosphatidylcholine (SFPC). Liposomes (SL) were generated with the aid of a novel, organic solvent free, and environmentally benign process which utilizes venturi-based rapid expansion of supercritical solution (Vent-RESS). Vitamins E and C were used as model lipophilic and hydrophilic bioactives and demonstrated an average encapsulation efficiency of 92 and 70 %, respectively. Synthesized liposomes were coated with a pH-responsive double-wall of chitosan and β-lactoglobulin (βlg-Cs-SL) to develop a biocompatible vehicle for pH-triggered delivery of bioactive cargo(s). To compare the efficacy of this newly developed dual-coating, SL was also coated with a commercially available pH responsive polymer, Eudragit® S100 (Eu-SL). No organic solvent was used during the surface coating of SLs with these two different types of enteric coatings. The performance of these two coatings was studied by conducting morphological characterization through diameter and ζ-potential measurements along with confocal laser scanning and freeze-fracture cryogenic scanning electron microscopies. The stability of coated and uncoated SFPC liposomes was determined in simulated gastrointestinal fluids. For βlg-Cs-SL and Eu-SL, after 2 h of incubation in simulated gastric condition, less than 5 % of the encapsulated vitamins C and E were released, whereas for SL, 41 and 28 % of vitamins C and E were released within 2 h of incubation period. In simulated intestinal fluid, coated liposomes released most of their remaining payload when incubated for 4 h. The newly developed dual coating was found to be as effective as its commercially available counterpart, Eudragit® S100 coating; nevertheless, the biocompatible, non-toxic, and non-synthetic nature of this coating makes it an attractive alternative. Modeling the release kinetics of vitamins from coated liposome showed that the release of payload from surface coated liposomes proceeded through a multistep structural disintegration involving both Fickian and non-Fickian types of diffusion. The ability of these surface-coated liposomes to maintain structural integrity under the gastric condition followed by site-specific, pH-triggered release of encapsulated cargo in the intestine will make them highly suitable for oral administration of bioactive compounds in pharmaceutical and food applications.

Polyprodrug with ultra-high drug content for tumor intracellular acid-triggered degradation and drug delivery

• Degradable polyprodrug was designed with drug as repeating units. • An ultrahigh drug content of 1.67 mmol/g was obtained. • Excellent pH-triggered degradation and drug release were achieved. • The pH-triggered degradation and drug release mechanism was proposed. Polyprodrugs are expected to possess better drug release performance than the conventional polymer prodrugs, because the drug molecules are conjugated in the main chain as structural units, different from the side groups or end groups in the later one. Here, acid-triggered degradable polyprodrug P(DOX-NH) was designed as drug self-delivery system (DSDS) for the tumor intracellular acid-triggered drug delivery, via a facile condensation polymerization of N-hydazinated doxorubicin (DOX-NH). Owing to the unique structure by direct connecting the DOX-NH repeating units via hydrazone bond with each other without any linker, an ultrahigh drug content of 1.67 mmol/g was achieved. Therefore, the chemotherapeutic drug DOX-NH could be released in the acidic tumor intracellular microenvironment, without any by-product. With the emulsification of PEGylated doxorubicin (DOX-PEG), prodrug nanoparticles (P(DOX-NH)@PEG-NP) were obtained with a mean hydrodynamic diameter of 167.4 ± 8.4 nm, possessing an excellent drug release property. Furthermore, the enhanced antitumor efficacy was obtained than free DOX in the in vitro cellular experiments, demonstrating the promising potential of the proposed polyprodrug for future tumor chemotherapy.

Stealth doxorubicin conjugated bimetallic selenium/silver nanoparticles for targeted cervical cancer therapy

Bimetallic nanosized delivery systems are attracting a lot of research interest as alternatives to monometallic delivery systems. This study evaluated the ability of bimetallic selenium silver chitosan pegylated folic acid targeted nanoparticles (SeAgChPEGFA NPs) to deliver doxorubicin (DOX) in cervical cancer cells. Comparison studies using monometallic selenium chitosan pegylated folic acid (SeChPEGFA NPs) targeted NPs and free DOX were also conducted. The prepared NPs and their drug nanocomplexes were characterised morphologically and physico-chemically. Drug binding and releasing studies were conducted under a simulated environment in vitro. The cytotoxicity and apoptosis studies were studied using the 3-[(4, 5-dimethylthiazol-2-yl)−2, 5-diphenyl tetrazolium bromide] (MTT) assay and the dual dye staining. The findings revealed that the bimetallic SeAgChPEGFA NPs displayed better colloidal stability, superior physico-chemical qualities, and higher binding abilities in comparison with monometallic SeChPEGFA NPs. In addition, the SeAgChPEGFA NPs showed the pH-triggered controlled drug release and cell-specific cytotoxicity. These findings suggest that the bimetallic NPs are superior delivery systems when compared to their monometallic NPs and free drug counterparts, thus, setting a platform for further in vivo examination.

Cerium containing pH-responsive microcapsule for smart coating application: Characterization and corrosion study

In the following paper first, novel pH-sensitive melamine-formaldehyde microcapsules containing ethylene glycol with three concentrations of cerium nitrate were synthesized. Then, three different quantities of the microcapsules were introduced to the epoxy coatings and applied on the AA2024-T3 substrate to meet the increasing demands for self-healing coatings. The characteristics of microcapsules were studied by scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared (FTIR), and dynamic light scattering (DLS). The UV–Vis spectroscopy was accomplished to the appraise pH-triggered release of the microcapsules. The salt spray test along with electrochemical impedance spectroscopy (EIS) was conducted for studying the anti-corrosion and self-healing proficiency of microcapsule-based coatings. The UV–Vis spectroscopy outcomes showed that the synthesized microcapsules are responsive to alkaline pH and the release rate of microcapsules in the basic medium rises with increasing the pH values. Moreover, the EIS and salt spray results indicated that incorporation of 10 wt% of the microcapsules into the epoxy coating not only improved the anti-corrosion strength of the aluminum substrate compared to neat epoxy coating remarkably but also, provided active corrosion protection of the substrate through the self-healing action of cerium ions. Also, the attendance of cerium cations in the scratch surface was confirmed by field emission scanning electron microscopy (FE-SEM) and energy-dispersive X-ray (EDX) map.

Advances in pH-responsive drug delivery systems

Bioresponsive nanosystems are increasingly important in a wide range of applications such as drug delivery, tissue engineering, imaging diagnostics and biosensors. Among these, pH-responsive delivery systems have gained considerable attention because of their ability in response to disease microenvironment and pH-triggered release of therapeutic drugs for therapy. In view of the importance of pH-sensitive nano-delivery systems, this review article highlights four types of pH-responsive modes, the corresponding design strategies, applications and future directions by smart design of pH-sensitive nanosystems for precision imaging or therapy.

Complementary Nucleobase Interactions Drive Co-Assembly of Drugs and Nanocarriers for Selective Cancer Chemotherapy.

A new concept in cooperative adenine–uracil (A–U) hydrogen bonding interactions between anticancer drugs and nanocarrier complexes was successfully demonstrated by invoking the co-assembly of water soluble, uracil end-capped polyethylene glycol polymer (BU-PEG) upon association with the hydrophobic drug adenine-modified rhodamine (A-R6G). This concept holds promise as a smart and versatile drug delivery system for the achievement of targeted, more efficient cancer chemotherapy. Due to A–U base pairing between BU-PEG and A-R6G, BU-PEG has high tendency to interact with A-R6G, which leads to the formation of self-assembled A-R6G/BU-PEG nanogels in aqueous solution. The resulting nanogels exhibit a number of unique physical properties, including extremely high A-R6G-loading capacity, well-controlled, pH-triggered A-R6G release behavior, and excellent structural stability in biological media. Importantly, a series of in vitro cellular experiments clearly demonstrated that A-R6G/BU-PEG nanogels improved the selective uptake of A-R6G by cancer cells via endocytosis and promoted the intracellular release of A-R6G to subsequently induce apoptotic cell death, while control rhodamine/BU-PEG nanogels did not exert selective toxicity in cancer or normal cell lines. Overall, these results indicate that cooperative A–U base pairing within nanogels is a critical factor that improves selective drug uptake and effectively promotes apoptotic programmed cell death in cancer cells.