Charge Reversal Research Articles

Antioxidant colloids via heteroaggregation of cerium oxide nanoparticles and latex beads

Antioxidant colloids were developed via controlled heteroaggregation of cerium oxide nanoparticles (CeO2 NPs) and sulfate-functionalized polystyrene latex (SL) beads. Positively charged CeO2 NPs were directly immobilized onto SL particles of opposite surface charge via electrostatic attraction (SL/Ce composite), while negatively charged CeO2 NPs were initially functionalized with poly(diallyldimethylammonium chloride) (PDADMAC) polyelectrolyte and then, aggregated with the SL particles (SPCe composite). The PDADMAC served to induce a charge reversal on CeO2 NPs, while the SL support prevented nanoparticle aggregation under conditions, where the dispersions of bare CeO2 NPs were unstable. Both SL/Ce and SPCe showed enhanced radical scavenging activity compared to bare CeO2 NPs and were found to mimic peroxidase enzymes. The results demonstrate that SL beads are suitable supports to formulate CeO2 particles and to achieve remarkable dispersion storage stability. The PDADMAC functionalization and immobilization of CeO2 NPs neither compromised the peroxidase-like activity nor the radical scavenging potential. The obtained SL/Ce and SPCe artificial enzymes are foreseen to be excellent antioxidant agents in various applications in the biomedical, food, and cosmetic industries.

The heteroaggregation and deposition behavior of nanoplastics on Al2O3 in aquatic environments

The ubiquitous Al2O3 is anticipated to interact with nanoplastics, affecting their fate and transport in aquatic environments. In this study, the heteroaggregation and deposition behaviors of polystyrene nanoplastics (PSNPs) on Al2O3 were systematically investigated under different conditions (ionic strength, pH, and natural organic matter). The results showed that significant heteroaggregation occurred between PSNPs and Al2O3 particles under acidic and neutral conditions. When the NaCl concentration was increased from 50 to 500 mM, the heteroaggregation ratio gradually increased. However, poly (acrylic acid) (PAA) inhibited the heteroaggregation of PSNPs-Al2O3 due to steric repulsion. The deposition of PSNPs on Al2O3 surfaces was inhibited as the NaCl concentration or pH values increased. Due to charge reversal and steric repulsion, humic acid (HA) and fulvic acid (FA) prevented the deposition of PSNPs onto Al2O3 surfaces, and the former was more effective in reducing the deposition rate. The interaction mechanism between PSNPs and Al2O3 was revealed by using various characterization techniques and density function theory (DFT) calculation. The results demonstrated that in addition to the dominant electrostatic interaction, there were also weak hydrogen bonds and van der Waals interactions. Our research is of great significance for predicting the migration and fate of PSNPs in aquatic environments.

Reversible Chemical Protein Modification to Endogenous Glutathione and Its Utilities in the Manufacture of Transcellular Pro-Enzymes

Proteins have been perceived as being an intriguing modality of therapeutics for the treatment of intractable diseases in view of their superlative precision and versatility. Nonetheless, proteins' intrinsic characters, particularly their being hydrophilic macromolecules with unmethodical charges, have imposed the exceeding challenge of seeking transcellular trafficking into cells' interiors. To circumvent this drawback, we have attempted to employ triple-functional amine-reactive 4-(2-((2-(((4-nitrophenoxy)carbonyl)oxy)ethyl)disulfaneyl)ethoxy)-4-oxobutanoic acid for the efficient incorporation of the anionic carboxyl moiety into amine-enriched enzymes, resulting in overall negatively charged pro-enzymes. The resulting pro-enzymes could be readily electrostatically assembled with cationic species [for instance: block copolymers of poly(ethylene glycol)-polylysine] into core-shell architectural delivery nanoparticles for their facilitated endocytosis into cells. Noteworthy is the aforementioned carboxylation chemistry designed to allow facile reversal of the pro-enzymes to the original amine groups due to the thiolysis of intermediate disulfide linkage for subsequent cascade reactions in response to the cytosol-enriched glutathione. Therefore, cytosol-selective structural disassembly for the liberation and activation of the pro-enzymes was accomplished. Our subsequent investigations utilizing ribonuclease A and catalase as the model enzymes demonstrated appreciable transcellular transportation of the active enzymes to the cell interiors, exerting overwhelming cytotoxic potencies and H2O2 scavenging capacities, respectively. Hence, we reported an unprecedented redox-stimulated charge reversal strategy in engineering cytosol-activatable pro-enzymes, manifesting a simple and efficient approach in the manufacture of transcellular proteinic therapeutics, which should be highlighted to promote their wide availability for use with diverse functional proteins as molecular biological tools and precision therapeutics.

Dual-pH responsive chitosan nanoparticles for improving in vivo drugs delivery and chemoresistance in breast cancer

Efficient intracellular drugs delivery and accumulation are the key determinant for overcoming tumor multidrug resistance (MDR). To realize this purpose, dual-pH responsive chitosan nanoparticles (DCCA/DOX-NPs) were fabricated to treat MDR tumor in human breast cancer (MCF-7/ADR). The particles were firstly sensitive to tumor extracellular pH 6.5, contributing to the surface charge reversal (−6.32 → 11.45 mV) by the cleavage of β-carboxylic amide, which greatly increased cellular uptake efficiency. DCCA/DOX-NPs further responded to lower intracellular pH 5.0, thereby triggering DOX and cinnamaldehyde (CA) release by the cleavage of Schiff base. Cells assays verified that dual-pH sensitive particles caused higher toxicity in MDR tumor cells. Furthermore, the particles could overcome tumor resistance by decreasing intracellular levels of ATP and PARP-1, eventually receiving stronger antitumor efficiency in vivo (84.94%). Overall, this amphiphilic chitosan nanosystem with various bioactivities could work as an alternative promising for treating MDR tumor.

Influence of combined natural deep eutectic solvent and polyacrylamide on the flocculation and rheological behaviors of bentonite dispersion

The influence of hybrid coagulation/ flocculation systems on the degree of flocculation and rheological behavior of highly stable bentonite suspension has been investigated throughout this study. Natural deep eutectic solvent (NADES) synthesized from choline chloride (ChCl) and lactic acid (LA) was utilized as the coagulant in the hybrid system at a fixed dosage of 1.78×10-2M. Two cationic polyacrylamides (CPAM) and two anionic polyacrylamides (APAM) with varying charge density (CD) were the studied flocculants in the hybrid system. The flocculation efficiency of the anionic and cationic hybrid systems (i.e., NADES/ FO 4350 SH, NADES/ FO 4800 SH, NADES/ AN 923 SH, and NADES/ AN 956 SH, respectively) was evaluated based on specified criteria, including the zeta potential, turbidity, floc size, and rheology of the treated suspension. Compared to a single system, the utilization of a hybrid system significantly influenced the treatment efficiency of APAMs and CPAMs. At an optimum APAM dosage of 10mgL-1 and 15mgL-1 for NADES/ AN 923 SH and NADES/ AN 923 SH, respectively, the systems showed an exceptional improvement with a turbidity removal >99%, zeta potential in the range of -10mV<ζ<0mV, and floc size >60μm. On the other hand, NADES with CPAMs (i.e., NADES/ FO 4350 SH and NADES/ FO 4800 SH) demonstrated a setback in their treatment efficiency due to the charge reversal exhibited by the hybrid systems hence, re-stabilization of the suspension. The conducted rheological analysis revealed that the studied hybrid systems could enhance the properties of produced sediment. The formation of larger, more compacted flocs resulted in nono-Newtonian shear-thinning sediment with a shear resistivity and elastic modulus more than ten times higher compared to the single systems. The tested hybrid systems with low CD CPAM and APAM (i.e., NADES/ FO 4350 SH and NADES/ AN 923 SH) achieved higher viscosity, elastic modulus, and shear resistivity than systems with high CD PAMs. Furthermore, APAM hybrid systems exhibited superior performance compared to CPAM hybrid systems. Consequently, the NADES/ AN 923 SH hybrid system was the most efficient for treating bentonite suspension resulting in viscosity of 223,340 mPa.s, an elastic modulus of 32,487 mPa, and yield stress of 694 mPa at the optimum coagulant/ flocculant dosage.

Modifications in surfactant-dependent phase behavior of colloidal nanoparticles under charge reversal

Modifications in the surfactant (ionic and non-ionic)-dependent phase behavior of the anionic silica nanoparticles have been investigated under charge reversal as induced through multivalent counterions. The stable one-phase system of nanoparticles-anionic surfactant transforms into a two-phase (aggregates) state on the addition of tetravalent electrolyte (ZrCl4). On the other hand, the two-phase nanoparticle-cationic surfactant system becomes one-phase in the presence of ZrCl4. Interestingly, for nanoparticle-non-ionic surfactant system, stable micelle-decorated one-phase undergoes transformation to a two-phase with increasing ZrCl4 concentration. The modifications in the phase behavior have been explained by the structural evolution and interplay of the underlying interactions in the system.

Multifunctional “ball-rod” Janus nanoparticles boosting Fenton reaction for ferroptosis therapy of non-small cell lung cancer

Ferroptosis is a newly found cell death mechanism, which could bypass apoptosis and reverse multidrug resistance of tumors. However, efficient induction of tumor ferroptosis remains a challenge. In this study, multifunctional “ball-rod” Janus nanoparticles (FTG/L&SMD) were constructed for non-small cell lung cancer (NSCLC) ferroptosis treatment. Protected by tannic acid (TA), FTG/L&SMD maintains long-term function in blood circulation, while modification by 2, 3-dimethylmaleic anhydride (DMMA) confers the FTG/L&SMD with pH-responsive charge reversal. Glucose oxidase (GOD) on FTG/L&SMD catalyzes glucose to produce H2O2. Then, iron ion converts H2O2 to highly active hydroxyl radicals (OH•) via Fenton reaction, leading to lethal lipid peroxidation (LPO) accumulation. Meanwhile, TA reduces Fe3+ to Fe2+ to boost Fenton reaction cycle. Sor down-regulated glutathione peroxidase 4 (GPX4) expression in another pathway to induce ferroptosis synergistically. In vitro studies have shown that compared with sorafenib (Sor), FTG/L&SMD not only has more efficient tumor targeting and higher cytotoxicity, but also inhibits tumor migration. In vivo antitumor therapy experiments demonstrate that FTG/L&SMD inhibits tumor growth efficiently, and its toxicity is negligible. In general, FTG/L&SMD can initiate Fenton reaction cycle and reinforced ferroptosis to kill tumor cells, which is a promising anti-tumor nano-drug for NSCLC.

Surface Flashover Induced by Metal Contaminants Adhered to Tri-Post Epoxy Insulators under Superimposed Direct and Lightning Impulse Voltages

Metal contaminants can distort the surface electric field of the tri-post epoxy insulator and cause serious surface charge accumulation, significantly reducing the insulation performance of the insulator under the superimposed DC and lightning impulse voltage. In this paper, an experimental platform for charge accumulation and surface flashover of tri-post epoxy insulators under the superimposed DC and lightning impulse voltage was built, by surface point measurement and charge inversion calculation, the surface charge distribution characteristics of tri-post insulators with attached particles was experimentally explored and the influence law of attached metal particles on the charge accumulation was discussed. The results show that metal particles can cause a surge in the surface charge density of the tri-post epoxy insulator, forming bipolar charge spots whose polarity is opposite to that of the adjacent electrodes. The adsorbed metal dust can cause the polarity reversal of adjacent surface charges, forming a large-area unipolar charge spot. Moreover, the flashover voltage of a tri-post insulator under DC superimposed lightning impulse voltage with a clean surface and attached metal particle was measured, and the synergistic induction mechanism of charge spot accumulation and metal particle discharge on the flashover along the face of the tri-post insulator is thereby revealed. Compared with the clean insulators, the surface flashover voltages of tri-post epoxy insulators with metal contaminants adhered decrease under the superimposed voltages of different polarities, but the decline amplitude is greater under the heteropolar composite voltage. When adhered to the middle of the insulator leg, the distribution range of bipolar charge spots is the widest, and the surface flashover voltage decreases sharply, which can drop by 32% compared with the absence of particles. In addition, when the metal dust adsorbed by the tri-post epoxy insulator has a wide distribution range, the impact of metal dust on the flashover voltage is greater than that of the attached metal particles, and its hazard cannot be ignored. The research results can provide a reference for the insulation test method and optimal design of the DC tri-post epoxy insulator.

Dual-responsive nanoparticles with transformable shape and reversible charge for amplified chemo-photodynamic therapy of breast cancer

Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention, which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6 (Ce6), hydrophilic chemotherapeutic drug berberrubine (BBR) and matrix metalloproteinase-2 (MMP-2) response peptide (PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6 (BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine (PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time. Due to the acidic tumor microenvironment, the PEG shell was detached from PEG-His@BPC attributing to protonation of the histidine, which achieved charge reversal, size reduction and enhanced tumor penetration. At the same time, enzyme cutting site was exposed, and the spherical nanoparticles could transform into nanofibers following the enzymolysis by MMP-2, while BBR was released to kill tumors by inducing apoptosis. Compared with original nanoparticles, the nanofibers with photosensitizer Ce6 retained within tumor site for a longer time. Collectively, we provided a good example to fully use the intrinsic properties of different drugs and linkers to construct tumor microenvironment-responsive charge reversal and shape transformable nanoparticles with synergistic antitumor effect.

Systematic Research on the Transport of Ball-Milled Biochar in Saturated Porous Media: Effect of Humic Acid, Ionic Strength, and Cation Types.

Ball-milled biochar (BMBC) is a typical engineering material that has promising application prospects in remediating contaminated soil and water. It is fundamental to rate the transport behaviors of BMBC in the underground environment before extensive use. In this study, the effects of the ubiquitous cations (Na+, Mg2+, and Al3+) and model organic matter (humic acid) on the transport of BMBC were investigated using laboratory column experiments. The results demonstrated the facilitated effect of HA on the transport of BMBC due to the negatively charged surface and steric effect under neutral conditions. HA and ionic strength manifested an antagonistic effect on the transport of BMBC, where the presence of one could weaken the effect from the other. We also found the charge reversal of the BMBC surface in the presence of Mg2+, thus enhancing the deposition of BMBC onto the medium surface. On the other hand, the charge reversal from Al3+-coupled acid conditions led to the restabilization and transport of BMBC in porous media. Therefore, the rational usage of BMBC is indispensable and more attention should be paid to the composition and change in underground water that might facilitate the transport of BMBC and thus lead to negative environmental implications.

Reversal of Electroosmotic Flow in Charged Nanopores with Multivalent Electrolyte.

We study the reversal of electroosmotic flow in charged cylindrical nanopores containing multivalent electrolyte. Dissipative particle dynamics is used to simulate the hydrodynamics of the electroosmotic flow. The electrostatic interactions are treated using 3D Ewald summation, corrected for a pseudo-one-dimensional geometry of the pore. We observe that, for sufficiently large surface charge density, condensation of multivalent counterions leads to the reversal of the pore's surface charge. This results in the reversal of electroosmotic flow. Our simulations show that the Smoluchowski equation is able to quantitatively account for the electroosmotic flow through the nanopore, if the shear plane is shifted from the position of the Stern contact surface.

Charge Reversal Polypyrrole Nanocomplex-Mediated Gene Delivery and Photothermal Therapy for Effectively Treating Papillary Thyroid Cancer and Inhibiting Lymphatic Metastasis.

As a traditional treatment for papillary thyroid cancer (PTC), surgical resection of diseased tissues often brings lots of inconveniences to patients, and the tumor recurrence and metastasis are difficult to avoid. Herein, we developed a gene and photothermal combined therapy nanosystem based on a polypyrrole (Ppy)-poly(ethylene imine)-siILK nanocomplex (PPRILK) to achieve minimally invasive ablation and lymphatic metastasis inhibition in PTC simultaneously. In this system, gelatin-stabilized Ppy mainly acted as a photothermal- and photoacoustic (PA)-responsive nanomaterial and contributed to its well-behaved photosensitivity in the near-infrared region. Moreover, gelatin-stabilized Ppy possessed a charge reversal function, facilitating the tight conjunction of siILK gene at physiological pH (7.35-7.45) and its automatic release into acidic lysosomes (pH 4.0-5.5); the proton sponge effect generated during this process further facilitated the escape of siILK from lysosomes to the cytoplasm and played its role in inhibiting PTC proliferation and lymphatic metastasis. With the guidance of fluorescence and PA bimodal imaging, gene delivery and Ppy location in tumor regions could be clearly observed. As a result, tumors were completely eradicated by photothermal therapy, and the recurrences and metastases were obviously restrained by siILK.

Mitochondrial Glutathione Depletion Nanoshuttles for Oxygen-Irrelevant Free Radicals Generation: A Cascaded Hierarchical Targeting and Theranostic Strategy Against Hypoxic Tumor.

An oxygen-irrelevant free radicals generation strategy has shown great potential in hypoxic tumor therapy. However, insufficient tumor accumulation, nonspecific intracellular localization, and the presence of highly reductive mitochondrial glutathione (GSH) dramatically hamper the free radicals therapeutic efficacy. Herein, a hierarchical targeting system was constructed by Fe-doped polydiaminopyridine nanoshuttles, indocyanine green (ICG), and an oxygen-irrelevant radicals generator (AIPH) to possess a negative charge. An acid-specific charge-reverse capability of the shuttles was achieved to enhance cell uptake in the tumor microenvironment (TME). In addition, the iron release occurs only in the acidic TME, which can be used as acidity enhancers to strengthen the charge-reverse process, thereby leading to more efficient tumor internalization and deep penetration. Moreover, such a nanosystem has significantly improved the delivery efficiency of nanoshuttles (16.06%) in the tumor tissues at 24 h postinjection, much higher than that of naked Fe-doped polydiaminopyridine (6.59%). More importantly, the nanoshuttles enable simultaneously mitochondria targeting and corresponding GSH depleting capability to show advantages in free radicals-based therapy after charge reversion, leading to a powerful tumor inhibition rate (>95%). The prescence of iron could allow for magnetic resonance imaging, while ICG allowed for photoacoustic imaging and fluorescence imaging to guide the therapeutic process. The remarkable features of the nanoshuttles may open a new avenue to explore an oxygen-irrelevant free radicals generating system for accurate cancer theranostics.

Adsorption of CTAB on Sapphire-c at High pH: Surface and Zeta Potential Measurements Combined with Sum-Frequency and Second-Harmonic Generation.

The adsorption of cetyltrimethylammonium bromide (CTA+Br-) on sapphire-c surfaces was studied at pH 10 below the surfactants' critical micelle concentration. The evolution of interfacial potentials as a function of CTAB concentration was characterized by surface and zeta potential measurements and complemented by molecular dynamic (MD) simulations as well as by second-harmonic (SHG) and vibrational sum-frequency generation (SFG) spectroscopy. The changes in interfacial potentials suggest that the negative interfacial charge due to deprotonated surface aluminols groups is neutralized and can be even overcompensated by the presence of CTA+ cations at the interface. However, SFG intensities from strongly hydrogen-bonded interfacial water molecules as well as SHG intensities decrease with both increasing CTAB concentration and the magnitude of the surface potential. They do not suggest a charge reversal at the interface, while the change in zeta potential is actually consistent with an apparent charge inversion. This can be qualitatively explained by results from MD simulation, which reveal adsorbed CTA+ cations outside a first strongly bound hydration layer of water molecules, where they can locally distort the structural order and replace some of the interfacial water molecules adjacent to the first layer. This is proposed to be the origin for the significant loss in SFG and SHG intensities with increasing CTAB concentration. Moreover, we propose that CTA+ can act as a counterion and enhance the occurrence of deprotonated surface aluminols that is consistent with the decrease in surface potential.

Preparation and Evaluation of Charge Reversal Solid Lipid Nanoparticles

The aim of this study was to design and investigate solid lipid nanoparticles (SLN) providing an intestinal alkaline phosphatase (IAP) triggered charge reversion.SLN containing the monophosphate ester bearing surfactant P-PEG-9-lauryl ether and the cationic surfactant benzalkonium chloride were prepared via step-wise hot microemulsion method enabling P-PEG-9-lauryl ether to accumulate the phosphate moiety on the surface of the particles accessible for IAP. Charge reversal SLN were characterized in vitro and ex vivo.SLN containing 10% of P-PEG-9-lauryl ether and 1% of cationic surfactant displayed a z-average of 92 nm and a PDI of 0.33 remaining stable over one year stored at 2–8 °C. An enzyme induced charge reversion from -18.4 mV to +16.5 mV correlated with the cleavage of 82% of the incorporated phosphate. SLN maintained their size during charge reversion, as no significant difference in z-average was observed. Mucin interaction studies revealed a higher interaction between SLN and mucins in the presence of IAP causing an increase in z-average from 190 nm to 2500 nm as well as a decrease in zeta potential from -26 mV to -17 mV. No significant change in z-average and zeta potential was observed when IAP was absent indicating lower mucin interaction of negatively charged particles. In contrast, higher interaction with cell membrane was evidenced by 85% hemolysis when SLN were pretreated with IAP, whereas control SLN without IAP resulted in 16% hemolysis. To investigate the phosphate cleavage by membrane bound IAP, SLN were incubated on excised rat intestinal mucosa and a significant higher release of phosphate was observed in comparison to samples treated with an enzyme inhibitor.Charge reversal SLN might be promising drug delivery systems for alkaline phosphatase bearing membranes that are covered by a mucus gel layer such as the intestine.

PH-Sensitive and Charge-Reversal Polymeric Nanoplatform Enhanced Photothermal/Photodynamic Synergistic Therapy for Breast Cancer.

As reported, breast cancer is one of the most common malignancies in women and has overtaken lung cancer as the most commonly diagnosed cancer worldwide by 2020. Currently, phototherapy is a promising anti-tumor therapy due to its fewer side effects, less invasiveness, and lower cost. However, its application in cancer therapeutics is limited by the incomplete therapeutic effect caused by low drug penetration and monotherapy. Herein, we built a charge-reversal nanoplatform (Ce6-PLGA@PDA-PAH-DMMA NPs), including polydopamine (PDA) and chlorin e6 (Ce6) for enhancing photothermal/photodynamic synergistic therapy. The PAH-DMMA charge-reversal layer enabled Ce6-PLGA@PDA-PAH-DMMA NPs to have long blood circulation at the normal physiological environment and to successfully realize charge reversal under the weakly acidic tumor microenvironment, improving cellular uptake. Besides, in vitro tests demonstrated that Ce6-PLGA@PDA-PAH-DMMA NPs had high photothermal conversion and greater anti-tumor activity than no charge-reversal nanoparticles, which overcame the limited tumor therapeutic efficacy of PTT or photodynamic therapy alone. Overall, the design of pH-responsive and charge-reversal nanoparticles (Ce6-PLGA@PDA-PAH-DMMA NPs) provided a promising approach for synergistic PTT/PDT therapy against breast cancer.

Depleting Tumor Infiltrating B Cells to Boost Antitumor Immunity with Tumor Immune-Microenvironment Reshaped Hybrid Nanocage.

Tumor infiltrating B cells (TIBs)-dependent immunotherapy has emerged as a promising method for tumor treatment. Depleting TIBs to boost antitumor immunity is a highly desirable yet challenging approach to TIBs-dependent immunotherapy. Herein, a tumor immune-microenvironment reshaped hybrid nanocage CPN-NLI/MLD coloaded with the Bruton's tyrosine kinase inhibitor ibrutinib, and cytotoxic drug docetaxel was developed for stepwise targeting TIBs and tumor cells, respectively. The tumor microenvironment responsive CPN-NLI/MLD promoted charge reversal and size reduction under acidic conditions (pH < 6.5). The accumulation of CPN-NLI/MLD in tumor tissues was achieved through CD13 targeting, and cellular uptake was increased due to the differ-targeting delivery. Targeting of docetaxel to tumor cells was achieved by the interaction of α-MSH modified on inner docetaxel-particle MLD and melanocortin-1 receptor on the surface of tumor cells. Targeting of ibrutinib to TIBs was achieved by the interaction of Neu5Ac modified on inner ibrutinib-particle NLI and CD22 on the surface of TIBs. The boosted antitumor immunity was achieved mainly by the inhibition of Bruton's tyrosine kinase activation mediated by ibrutinib, which reduced the proportion of TIBs, enhanced infiltration of CD8+ and CD4+ T cells, increased the secretion of immunogenic cytokines including IL-2 and IFN-γ, and inhibited the proliferation of regulatory T cells and secretion of immunosuppressive cytokines including IL-10, IL-4, and TGF-β. Furthermore, CPN-NLI/MLD improved the antitumor efficiency of chemoimmunotherapy by reshaping tumor immune-microenvironment by TIBs depletion. Taken together, CPN-NLI/MLD represents a promising method for effective tumor treatment and combination therapy by TIBs-dependent immunotherapy.

Programmed Stimuli-Responsive Carbon Dot-Nanogel Hybrids for Imaging-Guided Enhanced Tumor Phototherapy.

For harmonizing the contradiction of nanotheranostic agents between enhanced tumor accumulation and penetration, efficient cell internalization and fast elimination are key tactics for promoting their clinical applications. Herein, programmed stimuli-responsive poly(N-isopropylacrylamide)-carbon dot (PNIPAM-CD) hybrid nanogels are designed to address the abovementioned conflicts. The enlarged particle size of PNIPAM-CDs enables one to effectively improve their accumulation at tumor sites. Once the hybrid nanogels are docked in tumors and exposed to deep-red-light (660 nm) irradiation, heat and reactive oxygen species (ROS) are generated from the CDs, consequently activating photothermal therapy (PTT) and photodynamic therapy (PDT) effects and meanwhile inducing partial degradation of PNIPAM-CDs for deep tissue penetration. Further, enhanced cellular internalization of the functional components can be achieved owing to the pH-responsive charge reversal and temperature-dependent hydrophilic/hydrophobic conversion characteristics of PNIPAM-CDs. Finally, the overexpressed glutathione (GSH) in tumor cells would trigger further cleavage of the partially degraded hybrid nanogels, which is beneficial for their rapid clearance from the body. This work not only proposed a novel strategy to fabricate nanotheranostic agents using just a single functional component (i.e., the versatile CDs) to simplify the preparation process but also achieved effective delivery of agents into tumor cells by overcoming the multiple biological barriers to enhance therapeutic efficacy and decrease side effects.

Elucidation of the redox activity of Ca2MnO3.5 and CaV2O4 in calcium batteries using operando XRD: charge compensation mechanism and reversibility

Ca2MnO3.5 and CaV2O4 were found to be potentially interesting as positive electrode materials for calcium metal-based high-energy density batteries with DFT-predicted average voltages of 3.7 V and 2.5 V and energy barriers for Ca migration of 1.1 eV and 0.6 eV, respectively. Both compounds were prepared by solid state reaction under reducing atmospheres. Optimum conditions to achieve Ca2MnO3.5 comprised the reduction of Ca2MnO4 under NH3 gas at 420⁰C with a flow rate of 1200 ml/min while CaV2O4 was achieved by reduction of CaV2O6 at 700 ⁰C under H2 flow. Electrochemical oxidation of Ca2MnO3.5 in lithium or calcium cells resulted in the formation of an orthorhombic phase with cell parameter (a= 5.2891(1), b= 10.551(2), c= 12.1422(1)). Operando synchrotron radiation diffraction experiments indicate that the charge compensation mechanism is not related to Ca2+ extraction but to intercalation of F− (originated from electrolyte salt decomposition) into the anion vacancy position, as confirmed by EELS and EDS. This process was found to be irreversible. In the case of CaV2O4, oxidation induces the electrochemical extraction of calcium with the formation of an orthorhombic phase (space group Pbnm) with cell parameters a = 10.72008(9) Å, b = 9.20213(2) Å and c = 2.89418(3) Å. The process was also investigated via operando synchrotron radiation diffraction, with the oxidized phase being found to reintercalate Ca2+ ions upon reduction, with the formation of a solid solution. Preliminary cycling tests reveals a decrease in the polarization after the first cycle and call for further investigation of this system.

Preparation and Drug-Loading Properties of Amphoteric Cassava Starch Nanoparticles.

Based on the characteristics of charge reversal around the isoelectric point (pI) of amphoteric starch-containing anionic and cationic groups, amphoteric cassava starch nanoparticles (CA-CANPs) are prepared by a W/O microemulsion crosslinking method using (3-chloro-2-hydroxypropyl) trimethyl ammonium chloride as a cationic reagent and POCl3 as an anionic reagent, and the effects of preparation conditions on the particle size of the CA-CANPs are studied in detail in the present study. CA-CANPs with a smooth surface and an average diameter of 252 nm are successfully prepared at the following optimised conditions: a crosslinking agent amount of 15 wt%, an aqueous starch concentration of 6.0 wt%, an oil–water ratio of 10:1, a total surfactant amount of 0.20 g·mL−1, and a CHPTAC amount of 4.05 wt%. The pH-responsive value of the CA-CANPs can be regulated by adjusting the nitrogen–phosphorus molar ratio in the CA-CANPs. By using CA-CANPs with a pI of 6.89 as drug carriers and the paclitaxel (PTX) as a model drug, the maximum loading rate of 36.14 mg·g−1 is achieved, and the loading process is consistent with the Langmuir isotherm adsorption, with the calculated thermodynamic parameters of ΔH° = −37.91 kJ·mol−1, ΔS° = −10.96 J·mol−1·K−1 and ΔG° < 0. By testing the release rate in vitro, it is noted that the release rates of PTX in a neutral environment (37.6% after 96 h) and a slightly acidic environment (58.65% after 96 h) are quite different, suggesting that the CA-CANPs have the possibility of being a targeted controlled-release carrier with pH responsiveness for antitumor drugs.