Rationally designed catalytic nanoplatform for enhanced chemoimmunotherapy via deploying endogenous plus exogenous copper and remodeling tumor microenvironment.

Chemodynamic therapy represents a novel tumor therapeutic modality via triggering catalytic reactions in tumors to yield highly toxic reactive oxygen species (ROS). Nevertheless, low efficiency catalytic ability, potential systemic toxicity and inefficient tumor targeting, have hindered the efficacy of chemodynamic therapy. Herein, a rationally designed catalytic nanoplatform, composed of folate acid conjugated liposomes loaded with copper peroxide (CP) and chloroquine (CQ; a clinical drug) (denoted as CC@LPF), could power maximal tumor cytotoxicity, mechanistically via maneuvering endogenous and exogenous copper for a highly efficient catalytic reaction. Despite a massive autophagosome accumulation elicited by CP-powered autophagic initiation and CQ-induced autolysosomal blockage, the robust ROS, but not aberrant autophagy, underlies the synergistic tumor inhibition. Otherwise, this combined mode also elicits an early onset, above all, long-term high-level existence of immunogenic cell death markers, associated with ROS and aberrant autophagy -triggered endoplasmic reticulum stress. Besides, CC@LPF, with tumor targeting capability and selective tumor cytotoxicity, could elicit intratumor dendritic cells (mainly attributed to CQ) and tumor infiltrating CD8+ T cells, upon combining with PD-L1 therapeutic antibody, further induce significant anti-tumor effect. Collectively, the rationally designed nanoplatform, CC@LPF, could enhance tumor chemoimmunotherapy via deploying endogenous plus exogenous copper and remodeling tumor microenvironment.

A polyethylenimine functionalized porous/hollow nanoworm as a drug delivery system and a bioimaging agent.

A wormstructured and nanosized porous/hollow polyethyleneimine (PEI) functionalized Gd2O3/Fe3O4 composite was fabricated as a drug carrier and a bioimaging agent. The effect of PEI's chain length on the size and morphology of the nanoworm was investigated and the results indicated that the nanoworm modified with PEI (10,000 molecular weight) (designated as p-nanoworm) possessed a suitable size and a porous/hollow structure. Meanwhile, the p-nanoworm could effectively prevent the leakage of Gd ions under different pH conditions because of plenty of amino groups on their surface. Compared with contrast agents of clinical use, the p-nanoworm displayed MR enhancement with a high r1 relaxivity of 5.58 s(-1) mM(-1) per gadolinium atom. Cisplatin (CDDP), a clinical anticancer drug, could be easily loaded into the pores and lumen of the p-nanoworm (p-nanoworm-CDDP) and also controllably released by adjusting the pH value. Cell assay suggested that the p-nanoworm possessed satisfactory biocompatibility and meanwhile could promote CDDP uptake of HeLa cells and enhance the inhibition effect on HeLa cells. In addition, p-nanoworm-CDDP showed a negligible cytotoxicity on normal human cells, indicating that the side effect of CDDP is reduced. Thus, the p-nanoworm could have a potential application for the diagnosis and therapy of cancer.

Dental Caries Management with Antibacterial Silver-Doped Prussian Blue Hydrogel by the Combined Effects of Photothermal Response and Ion Discharge.

Caries is a destructive condition caused by bacterial infection that affects the hard tissues of the teeth, significantly reducing the quality of life for individuals. Photothermal therapy (PTT) offers a noninvasive and painless treatment for caries, but the use of unsafe laser irradiance limits its application. To address this challenge, we prepared nanoparticles of silver ion-doped Prussian blue (AgPB), which was encased within cationic guar gum (CG) to form the antibacterial PTT hydrogel CG-AgPB with a photothermal conversion efficiency of 34.4%. When exposed to an 808 nm laser at a power density of 0.4 W/cm2, the hydrogel readily reached a temperature of over 50 °C in just 3 min, synchronized by the discharge of Ag+ ions from the interstitial sites of AgPB crystals, resulting in broad-spectrum and synergistic antibacterial activities (>99%) against individual oral pathogens (Streptococcus sanguinis, Streptococcus mutans, and Streptococcus sobrinus) and pathogen-induced biofilms. In vivo, CG-AgPB-mediated PTT demonstrated a capability to profoundly reduce the terminal number of cariogenic bacteria to below 1% in a rat model of caries. Given the outstanding biocompatibility, injectability, and flushability, this CG-AgPB hydrogel may hold promise as a next-generation oral hygiene adjunct for caries management in a clinical setting.

Infrared-Light-Responsive Controlled-Release Pesticide Using Hollow Carbon Microspheres@Polyethylene Glycol/α-Cyclodextrin Gel.

Controlled release of pesticides by light regulation is one of the most viable strategies recently developed for the highly efficient utilization of agrochemicals. Herein, we report an infrared-light-responsive pesticide delivery system for the controlled release of imidacloprid (IMI) by preparation of functional hollow carbon microspheres (HCMs). After IMI loading and surface functionalization with polyethylene glycol (PEG) and α-cyclodextrin (α-CD), IMI was sequestered in the pesticide system (denoted as HCMs/IMI/PEG/α-CD) as a result of the formation of a PEG/α-CD gel network. Upon the irradiation of infrared light, HCMs with high photothermal conversion efficiency (42.8%) raised the local temperature effectively, leading to the collapse of the gel network and the release of IMI. In comparison to the amount of pesticide release (29%) under sunlight, it could reach 77% driven by infrared light, which was an intriguing improvement. Consequently, HCMs/IMI/PEG/α-CD under infrared light showed significantly higher pest control efficacy on corn borers by 125% than itself alone. This work provides a promising method to intentionally regulate pesticide release and enhance utilization efficiency.

Electrical-Driven Release and Migration of Herbicide Using a Gel-Based Nanocomposite.

In this work, an electrical-driven release and migration glyphosate (EDRMG) was fabricated using a nanocomposite made up of attapulgite (ATP), glyphosate (Gly), and calcium alginate (CA). Therein, ATP-CA acted as a nanonetwork-structured carrier to efficiently load plenty of Gly to form porous ATP-Gly-CA hydrogel spheres (actually EDRMG-0.5) via a cross-linking reaction. The pores in EDRMG-0.5 hydrogel spheres were enlarged under an electric field because of the Coulomb force of the anionic CA polymer, and the release of negatively charged Gly from the spheres could be driven by the electric field force. Thus, EDRMG-0.5 exhibited a great electroresponsively controlled-release property, which was confirmed by a pot experiment. Importantly, the EDRMG-0.5 hydrogel spheres had fine biocompatibility on fish and mice, displaying good biosafety. This work provides a low cost and promising approach to control Gly release, deliver Gly precisely, and improve utilization efficiency, which might have a high application value.

Honeycomb-like magnetic cornstalk for Cr(VI) removal and ammonium release.

In this work, cornstalk (CS) was irradiated by high energy electron beam to obtain honeycomb-like porous CS (PCS). The PCS was loaded with ammonium sulfite (AS) and then coated by polyvinyl alcohol (PVA)-Fe3O4 to obtain PCS-AS@PVA-Fe3O4. The PCS-AS@PVA-Fe3O4 could reduce hexavalent chromium (Cr(VI)) to trivalent chromium (Cr(III)) by SO32-, then the Cr(III) combined with PCS-AS@PVA-Fe3O4 through hydrogen bonds. The resulting PCS-AS@PVA-Fe3O4/Cr with a high magnetism could be conveniently separated from water via a magnet. PCS-AS@PVA-Fe3O4/Cr showed a high performance on controlling Cr(VI) migration in soil and uptake by plant. Meanwhile, ammonium could be released from PCS-AS@PVA-Fe3O4, favoring plant growth. Therefore, this work not only provides a promising and low-cost approach to remove Cr(VI) and promote plant growth simultaneously, but also provides a new route for CS recycling, which might have a potential application value.

A biodegradable MnSiO3@Fe3O4 nanoplatform for dual-mode magnetic resonance imaging guided combinatorial cancer therapy.

In this work, a tumor microenvironment (TME)-responsive biodegradable MnSiO3@Fe3O4 nanoplatform for dual-mode magnetic resonance imaging (MRI)-guided combinatorial cancer therapy was constructed. Fe3O4 nanoparticles decorated on the surface of MnSiO3 could effectively obstruct the pores of MnSiO3 and reduce the leakage of anticancer drugs under physiological conditions. The structure of the nanoplatform was broken under the weakly acidic and high-concentration glutathione conditions in the TME, resulting in the separation of the Fe3O4 nanoparticles from the nanoplatform and rapid drug release. In addition, the exfoliated Fe3O4 and released Mn2+ can help reduce the interference between their T1 and T2 contrast abilities, resulting in dual-mode MRI contrast enhancement. Furthermore, during the exfoliation process of the Fe3O4 nanocrystals, the catalytic activity of the Fe3O4 nanocrystals toward a Fenton-like reaction within cancer cells could be improved because of the increase in specific surface area, which led to the generation of highly toxic hydroxyl radicals and induced HeLa cell apoptosis. The nanoplatform also displayed excellent T1-T2 dual-mode MRI contrast enhancement and anticancer activity in vivo with reduced systemic toxicity. Thus, this multifunctional nanoplatform could be a potential nanotheranostic for dual-mode MRI-guided combinatorial cancer therapy.

"Primitive" membrane from polyprenyl phosphates and polyprenyl alcohols.

Polyprenyl phosphates, as well as polyprenyl alcohols bearing different isopentenyl C(5) units, have been synthesized. The pH range of spontaneous vesicle formation of polyprenyl phosphates with or without polyprenyl alcohols was defined by fluorescence microscopy. A variety of the acyclic or monocyclic polyprenyl phosphates studied formed stable vesicles in water over a wide range of pHs, and the addition of polyprenyl alcohols allowed the vesicle formation of polyprenyl phosphates at higher pHs. Osmotic swelling of a suspension of unilamellar vesicles using the stopped-flow/light-scattering method enabled us to evaluate the water permeability of polyprenyl phosphate vesicles with or without 10 mol% of free polyprenyl alcohol. The addition of many polyprenyl alcohols to polyprenyl phosphate vesicles decreased the water permeability, and some reduced it even more efficiently than cholesterol.

A pH-Responsive Yolk-Like Nanoplatform for Tumor Targeted Dual-Mode Magnetic Resonance Imaging and Chemotherapy.

Incorporation of T1 and T2 contrast material in one nanosystem performing their respective MR contrast role and simultaneously serving as an efficient drug delivery system (DDS) has a significant potential application for clinical diagnosis and chemotherapy of cancer. However, inappropriate incorporation always encountered many issues, such as low contact area of T1 contrast material with water-proton, inappropriate distance between T2 contrast material and water molecule, and undesirable disturbance of T2 contrast material for T1 imaging. Those issues seriously limited the T1 or T2 contrast effect. In this work, we developed a yolk-like Fe3O4@Gd2O3 nanoplatform functionalized by polyethylene glycol and folic acid (FA), which could efficiently exert their tumor targeted T1-T2 dual-mode MR imaging and drug delivery role. First, this nanoplatform possessed a high longitudinal relaxation rate (r1) (7.91 mM-1 s-1) and a stronger transverse relaxation rate (r2) (386.5 mM-1 s-1) than that of original Fe3O4 (268.1 mM-1 s-1). Second, cisplatin could be efficiently loaded into this nanoplatform (112 mg/g) and showed pH-responsive release behavior. Third, this nanoplatform could be effectively internalized by HeLa cells with time and dosage dependence. Fourth, the FA receptor-mediated nanoplatform displayed excellent T1-T2 dual mode MR contrast enhancement and anticancer activity both in vitro and in vivo. Fifth, no apparent toxicity for vital organs was observed with systemic delivery of the nanoplatform in vivo. Thus, this nanoplatform could be a potential nanotheranostic for tumor targeted T1-T2 dual-mode MR imaging and chemotherapy.

Hydroxylated Mesoporous Nanosilica Coated by Polyethylenimine Coupled with Gadolinium and Folic Acid: A Tumor-Targeted T(1) Magnetic Resonance Contrast Agent and Drug Delivery System.

A pH-responsive nanoplatform, hydroxylated mesoporous nanosilica (HMNS) coated by polyethylenimine (PEI) coupled with gadolinium and folic acid (FA) (Gd-FA-Si), was designed to deliver anticancer drug targeting and to promote contrast effect for tumor cells using magnetic resonance (MR) spectrometer. Doxorubicin (DOX) was chosen as the anticancer drug and loaded into nanopores of HMNS, then its release in simulated body fluid could be controlled through adjusting the pH. This nanoplatform could significantly enhance the MR contrast effect, and the highest theoretical relaxivity per nanoplatform could even be approximately 1.28 × 10(6) mm(-1)s(-1) because of the high Gd payload (2.61 × 10(5) per nanoplatform). The entire system possessed a high targeting performance to Hela and MDA-MB-231 cells because the FA located in the system could specifically bind to the folate-receptor sites on the surface of cell. Compared with free DOX, the nanoplatform presented a higher cell inhibition effect on the basis of cell assay. Therefore, this nanoplatform could be potentially applied as a tumor-targeted T1 MR contrast agent and pH-sensitive drug carrier system.

Lipid membrane immobilized horseradish peroxidase biosensor for amperometric determination of hydrogen peroxide.

Stable films of didodecyldimethylammonium bromide (DDAB, a synthetic lipid) and horseradish peroxidase (HRP) were made by casting the mixture of the aqueous vesicle of DDAB and HRP onto the glassy carbon (GC) electrode. The direct electron transfer between electrode and HRP immobilized in lipid film has been demonstrated. The lipid films were used to supply a biological environment resembling biomembrane on the surface of the electrode. A pair of redox peaks attributed to the direct redox reaction of HRP were observed in the phosphate buffer solution (pH 5.5). The cathodic peak current increased dramatically while anodic peak decreased by addition of small amount H(2)O(2). The pH effect on amperometric response to H(2)O(2) was studied. The biosensor also exhibited fast response (5 s), good stability and reproducibility.

[Optimal effects of liposome on antisense oligodeoxynucleotides uptake by mouse breast cancer TM40D cells and the effects of antisense oligodeoxynucleotides targeting c-erbB-2 on cell proliferation and apoptosis].

OBJECTIVE: To study the optimal effects of liposome on antisense oligodeoxynucleotides targeting c-erbB-2 uptake by mouse breast cancer TM40D cells and effects of AS-ODNs on cell proliferation and apoptosis. METHODS: Flow cytometric analysis and fluorescence microscope were used to study the transfection ratio of AS-ODNs in mouse breast cancer TM40D cells with/without liposome in 1, 2, 4, 6 hour and the distribution of AS-ODNs in cells. the effects of ODNs on cell proliferation and activation of apoptosis were examined by MTT assay and flow cytometry. RESULTS: Liposome could promote AS-ODNs uptake by mouse breast cancer TM40D cells, flow cytometric analysis revealed that the time of the optimal effects was 4 hours and the percentage of FAM-positive cells reached 72.23%; the ratio maintained at a relatively high level at 6 h. Also liposome facilitated the entrance of AS-ODNs into nucleus. AS-ODNs restrained the proliferation of mouse breast cancer TM40D cells, and restraint rate was 50.24%. Meanwhile AS-ODNs promoted cell apoptosis. Flow cytometry analysis revealed that antisense ODNs increased cell apoptosis by 38.50%, compared with cultured cells group 9.13% and liposome group 9.29%. CONCLUSIONS: Liposome could facilitate AS-ODNs to enter cells and their nucleus. AS-ODNs of C-erbB-2 restrained the proliferation of mouse breast cancer TM40D cells and promoted apoptosis.

Composite of functional mesoporous silica and DNA: an enzyme-responsive controlled release drug carrier system.

An efficient enzyme-responsive controlled release carrier system was successfully fabricated using single-stranded DNA encapsulated functional mesoporous silica nanoparticles. Mesoporous silica nanoparticles were initially fabricated through hydrolysis of tetraethyl orthosilicate (TEOS) in cetyltrimethylammonium chloride (CTAC) solution, and the surface of nanoparticles could be encapsulated with single-stranded DNA. This nanomaterial has excellent bioactivity and its hydrolysate cannot cause damage to normal cell, thus the biocompatibility of the nanomaterial is improved. In addition, this nanomaterial showed an excellent drug release performance when loaded with drugs, which would be helpful to increase the treatment efficiency and decrease side effects of drugs.

Controlling nitrogen migration through micro-nano networks.

Nitrogen fertilizer unabsorbed by crops eventually discharges into the environment through runoff, leaching and volatilization, resulting in three-dimensional (3D) pollution spanning from underground into space. Here we describe an approach for controlling nitrogen loss, developed using loss control fertilizer (LCF) prepared by adding modified natural nanoclay (attapulgite) to traditional fertilizer. In the aqueous phase, LCF self-assembles to form 3D micro/nano networks via hydrogen bonds and other weak interactions, obtaining a higher nitrogen spatial scale so that it is retained by a soil filtering layer. Thus nitrogen loss is reduced and sufficient nutrition for crops is supplied, while the pollution risk of the fertilizer is substantially lowered. As such, self-fabrication of nano-material was used to manipulate the nitrogen spatial scale, which provides a novel and promising approach for the research and control of the migration of other micro-scaled pollutants in environmental medium.

Protein translocation through anthrax toxin channels formed in planar lipid bilayers.

The 63-kDa fragment of the protective antigen (PA) component of anthrax toxin forms a heptameric channel, (PA63)7, in acidic endosomal membranes that leads to the translocation of edema factor (EF) and lethal factor (LF) to the cytosol. It also forms a channel in planar phospholipid bilayer membranes. What role does this channel play in the translocation of EF and LF? We report that after the 263-residue N-terminal piece of LF (LFN) binds to its receptor on the (PA63)7 channel and its N-terminal end enters the channel at small positive voltages to block it, LFN is translocated through the channel to the opposite side at large positive voltages, thereby unblocking it. Thus, all of the translocation machinery is contained in the (PA63)7 channel, and translocation does not require any cellular proteins. The kinetics of this translocation are S-shaped, voltage-dependent, and occur on a timescale of seconds. We suggest that the translocation process might be explained simply by electrophoresis of unfolded LFN through the channel, but the refolding of the N-terminal half of LFN as it emerges from the channel may also provide energy for moving the rest of the molecule through the channel.