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Various attributes of micelles, such as PEG density and particle size, are considered to be related to blood clearance. The structural stability of micelles is another key attribute that will affect the in vivo fate. This study employed fluorescence resonance energy transfer (FRET) analysis to guide the preparation of polymeric micelles with different structural stability. Micelles prepared using copolymers with longer hydrophobic blocks showed higher structural stability; emulsification was a better method than nanoprecipitation to prepare stable micelles. The fast chain exchange kinetics and the high-water content of micellar cores explained the low structural stability of those micelles. Moreover, this study highlighted the importance of structural stability that affected blood clearance in concert with PEG length and particle size. One-third of the small and stable micelles were detected in the blood 24 h after injection. While unstable micelles would be cleared from the circulation within 4 h. Notably, there would be a threshold of structural stability. Micelles with structural stability below this threshold were quickly cleared even if they possessed a longer PEG length and a smaller size. In contrast, higher structural stability allowed polymeric micelles to maintain higher integrity in vivo and enhance tumor accumulation and anti-tumor efficacy. In conclusion, this study systematically analyzed the importance of the structural stability of micelles on the in vivo fate. [Display omitted] • FRET is a suitable method for characterizing micelle stability. • The chain exchange rate and core water content affect the micelle stability. • The key to the rapid clearance of small micelle is rapid dissociation. • Premature dissociation of micelles is detrimental to tumor delivery. [ABSTRACT FROM AUTHOR]

In the pursuit of high-energy-density lithium batteries, composite solid-state electrolytes are highly favored due to the combination of flexibility and acceptable ionic conductivity. However, challenges such as unpredictable lithium dendrite growth, cathode material structural instability, and oxidative resistance at high voltages pose significant hurdles for solid-state batteries. To investigate the synergistic interactions of polymers and sulfides, a hybrid poly (1,3-dioxolane) and poly (polyethylene glycol diacrylate) blend was designed through in-situ polymerization, allowing LiFePO 4 //Li batteries to achieve an average coulombic efficiency exceeding 99% at 0.5C and stable cycling for at least 1000 h in lithium symmetric cells. Computational analysis and component detection demonstrate the stability of the components and the formation of a LiF-stabilized anode from lithium salt decomposition. Similarly, on the cathode side, when Li 3 PO 4 -coated LiNi 0.6 Co 0.2 Mn 0.2 O 2 is used as the cathode material, a more stable interface suppresses cathode particles' collapse and harmful electrolytes' decomposition. In ambient environments, after 200 cycles at 0.5C, the capacity retention remains as high as 90.48%. Impedance changes by in-situ methods and component composition were further analyzed. This work integrates multiple methods and stabilizes and validates the anode and cathode interface, providing a promising approach and strategy for designing high-performance sulfide composite solid-state batteries. [Display omitted] • In-situ polymerization designs sulfide-compatible composite solid-state electrolytes. • Enhanced mechanical properties assists to form a stable interface to inhibit lithium dendrites penetration. • The conversion of residual lithium into a Li 3 PO 4 nano-coating achieves the nickel-rich cathode stability. • The principle of understanding interface evolution through in-situ impedance and interface composition is proposed. [ABSTRACT FROM AUTHOR]

Nano drug delivery systems have attracted researchers' growing attention and are gradually emerging into the public views. More and more nano-formulations are being approved for marketing or clinical use, representing the field's booming development. Copolymer self-assembly systems such as micelles, nanoparticles, polymersomes occupy a prominent position in the field of nano-drug delivery carriers. Among them, polymersomes, unlike micelles or nanoparticles, resemble liposomes' structure and possess large internal hollow hydrophilic reservoirs, allowing them to carry hydrophilic drugs. Nevertheless, their insufficient drug loading efficiency and unruly self-assembly morphology have somewhat constrained their applications. Especially for the delivery of biomacromolecule such as peptides, the encapsulation efficiency is always considered to be a formidable obstacle, even if the enormous hydrophilic core would render the polymersomes to have considerable potential in this regard. Reassuringly, the emergence of asymmetric polymersomes holds the prospect of solving this problem. With the development of synthetic technology and a deeper understanding of the self-assembly process, the asymmetric polymersomes which are with different inner and outer shell composition have been gradually recognized by researchers. It has made possible elevated drug loading, more controllable assembly processes and release performance. The internal hydrophilic blocks different from the outer shell could be engineered to have a more remarkable affinity to the cargos or could contain a non-watery aqueous phase to enable the thermodynamically preferred encapsulation of cargos, which would allow for a substantial improvement in drug encapsulation efficiency compared to the conventional approach. In this paper, we aim to deepen the understanding to asymmetric polymersomes and lay the foundation for the development of this field by describing four main elements: the mechanism of their preparation and asymmetric membrane formation process, the characterization of asymmetric membranes, the efficient drug loading, and the special stimulus-responsive release mechanism. [Display omitted] [ABSTRACT FROM AUTHOR]

Occupational crystalline silica (CS) particle exposure leads to silicosis. The burden of CS-associated disease remains high, and treatment options are limited due to vague mechanisms. Here we show that pulmonary CD4+ tissue-resident memory T cells (TRM) accumulate in response to CS particles, mediating the pathogenesis of silicosis. The TRM cells are derived from peripheral lymphocyte recruitment and in situ expansion. Specifically, CD69+CD103+ TRM-Tregs depend more on circulating T cell replenishment. CD69 and CD103 can divide the TRM cells into functionally distinct subsets, mirroring the immuno-balance within CD4+ TRM cells. However, targeting CD103+ TRM-Tregs do not mitigate disease phenotype since the TRM subsets exert immunosuppressive but not pro-fibrotic roles. After identifying pathogenic CD69+CD103- subsets, we highlight IL-7 for their maintenance and function, that present a promising avenue for mitigating silicosis. Together, our findings highlight the distinct role of CD4+ TRM cells in mediating CS-induced fibrosis and provide potential therapeutic strategies. Crystalline silica exposure led to CD4+ tissue-resident memory T-cell accumulation. The imbalance of pulmonary TRM-Teffs and TRM-Tregs promoted silicosis progression. Neutralizing IL-7 alleviated silicosis by disrupting TRM-Teff maintenance. [ABSTRACT FROM AUTHOR]

Photodynamic therapy has always been an antibacterial tool for solving multi-drug resistant bacteria problem, but the side effects and the low efficiency due to the high aggregation and low solubility of photosensitizers limit its application. Due to the anti-inflammatory effect of caffeic acid, two novel photosensitizers (CA-1-TBO, CA-TBO) were synthesized by conjugating caffeic acid with toluidine blue O (TBO). The structures have been characterized by 1HNMR and high-resolution mass spectrometry. The UV–vis absorption, fluorescence spectra and the octanol-water partition coefficient of two photosensitizers were measured to evaluate their photophysical properties and hydrophilic/hydrophobic properties. Compared with parent TBO, the two modified photosensitizers have shown a higher quantum yield and kinetics constants of singlet oxygen, which has been supported by the simulation results of density functional theory. As drug-resistant representatives of gram-positive and gram-negative bacteria, respectively, S. aureus and P. aeruginosa have been used for in vitro antibacterial experiments. The sterilization efficiencies of the two modified photosensitizers far exceed that of parent TBO. The results of the octanol-water partition coefficient and fluorescence quantification showed that modified photosensitizers CA-1-TBO and CA-TBO could be more accumulated than parent TBO. Based on scanning electron microscopy images, protein gel electrophoresis, and the conductivity of the bacterial solution, the possible mechanism of improved antibacterial photodynamic efficiencies could be induced by membrane permeability due to the caffeic acid effect. The findings demonstrate the significant potential of natural phenolic compounds in the development of photosensitizer molecules with characteristics such as more efficient, biocompatible and less side effects. • Novel photosensitizers from caffeic acid and toluidine blue O have been prepared. • CA-1-TBO and CA-TBO can penetrate bacterial membranes. • CA-1-TBO and CA-TBO could accumulate efficiently into bacterial cells. • CA-1-TBO and CA-TBO showed the enhanced aPDT efficiency. • CA-1-TBO and CA-TBO could target intracellular proteins. [ABSTRACT FROM AUTHOR]

Exposure to crystalline silica (CS) particles in worksites and dwellings can lead to silicosis due to excessive fibroblast activation. Considering their immuno-regulatory activities, the contribution of pulmonary fibroblasts in the progression of silicosis has not been thoroughly characterized. Here, we demonstrate that exposure of the lung to CS particles leads to the upregulation of fibroblast-derived C-X-C motif chemokine ligand 14 (CXCL14). By employing an in vitro co-culture system, we demonstrated activated fibroblasts recruited bone marrow–derived macrophages (BMDMs) and favored alternative macrophage polarization (M2) mediated by CXCL14. Furthermore, in vivo studies echoed that systemic CXCL14 neutralizing or fibroblast-specific Cxcl14 knockout proved CXCL14 was indispensable for the recruitment and phenotype alteration of lung macrophages, especially interstitial macrophages (IMs), under stimulation by CS particles. Mechanistically, we showed that GLI2 and p21-mediated cellular senescence were mediators of CXCL14 production following CS exposure. Accordingly, GLI2 blockage and countering cellular senescence by reviving PINK1-mediated mitophagy may be efficient strategies to reduce CXCL14 expression in activated fibroblasts during silicosis. Our findings emphasize the immuno-regulatory function of fibroblasts in silicosis via CXCL14, providing intervention targets for CS-induced pulmonary fibrosis. [Display omitted] • Crystalline silica exposure leads to fibroblast-derived CXCL14 upregulation. • Fibroblast-derived CXCL14 recruits and alternates lung interstitial macrophages. • CXCL14 production is regulated by GLI2 and p21-mediated cellular senescence. [ABSTRACT FROM AUTHOR]

[Display omitted] During the last two decades, an increasing number of reports have pointed out that the immunogenicity of polyethylene glycol (PEG) may trigger accelerated blood clearance (ABC) and hypersensitivity reaction (HSR) to PEGylated nanoparticles, which could make PEG modification counterproductive. These phenomena would be detrimental to the efficacy of the load and even life-threatening to patients. Consequently, further elucidation of the interplay between PEGylated nanoparticles and the blood immune system will be beneficial to developing and applying related formulations. Many groups have worked to unveil the relevance of structural factors, dosing schedule, and other factors to the ABC phenomenon and hypersensitivity reaction. Interestingly, the results of some reports seem to be difficult to interpret or contradict with other reports. In this review, we summarize the physiological mechanisms of PEG-specific immune response. Moreover, we speculate on the potential relationship between the induction phase and the effectuation phase to explain the divergent results in published reports. In addition, the role of nanoparticle-associated factors is discussed based on the classification of the action phase. This review may help researchers to develop PEGylated nanoparticles to avoid unfavorable immune responses based on the underlying mechanism. [ABSTRACT FROM AUTHOR]

The oral route has long been recognized as the most preferred route for drug delivery as it offers high patient compliance and requires minimal expertise. Unlike small molecule drugs, the harsh environment of the gastrointestinal tract and low permeability across the intestinal epithelium make oral delivery extremely ineffective for macromolecules. Accordingly, delivery systems that are rationally constructed with suitable materials to overcome barriers to oral delivery are exceptionally promising. Among the most ideal materials are polysaccharides. Depending on the interaction between polysaccharides and proteins, the thermodynamic loading and release of proteins in the aqueous phase can be realized. Specific polysaccharides (dextran, chitosan, alginate, cellulose, etc.) endow systems with functional properties, including muco-adhesiveness, pH-responsiveness, and prevention of enzymatic degradation. Furthermore, multiple groups in polysaccharides can be modified, which gives them a variety of properties and enables them to suit specific needs. This review provides an overview of different types of polysaccharide-based nanocarriers based on different kinds of interaction forces and the influencing factors in the construction of polysaccharide-based nanocarriers. Strategies of polysaccharide-based nanocarriers to improve the bioavailability of orally administered proteins/peptides were described. Additionally, current restrictions and future trends of polysaccharide-based nanocarriers for oral delivery of proteins/peptides were also covered. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] Chemotherapy is an effective anti-tumor treatment. Some anticancer chemotherapeutic drugs can not only induce cell death, but can also elicit antitumor immune responses. Here, the stability of cisplatin-loaded polymeric micelles (CDDP-PMs), pharmacokinetic drug-drug interactions of CDDP and anti-PD-L1 antibody (aPD-L1) in vivo and the alteration of the tumor microenvironment by combination of CDDP-PMs and aPD-L1 were evaluated. CDDP-PMs were fabricated by coordinated complexation and self-assembly method for tumor targeting. CDDP-PMs with higher mass ratio of copolymer have higher thermodynamic stability. The pharmacokinetic study showed that the CDDP and aPD-L1 were metabolized and cleared by two different pathways, suggesting that there is almost no risk of potential drug interactions between CDDP and aPD-L1 and the combination of aPD-L1 and CDDP- PMs may not alter the tissue distribution of CDDP. In vivo antitumor test showed that the tumor growth inhibition rates of CDDP-PMs combined with medium-dose aPD-L1 and CDDP-PMs combined with high-dose PD-L1 were 89.41% and 93.16%, respectively and therapeutic efficacy can be further increased by increasing the dose of aPD-L1 in co-administration group. This therapeutic system by combining chemotherapy and immunotherapy further increases the link between them and holds great potential to offer better safety and antitumor efficacy profiles. [ABSTRACT FROM AUTHOR]

Interfacial side reaction is a major problem faced by solid state electrolyte (SSE), especially the oxidation reaction between high-voltage cathode materials and SSE. Herein, a double-layer PVCA-ETPTA|LAGP-PPC Janus solid electrolyte (JSE) with ultra-high interfacial stability is successfully designed. An oxidation tolerant cross-linked poly (Vinylene Carbonate) (PVCA)-Ethoxylated trimethylolpropane triacrylate (ETPTA) electrolyte is used on the cathode side, resulting in a stable interfacial layer under high-voltage. To enhance the stability of SSE|Li interface, a protective Li 1.5 Al 0.5 Ge 1.5 P 3 O 12 (LAGP)-Poly (propylene carbonate) (PPC) layer is adhered to Li metal. The obtained dual-layer structure shows great thermal stability with an electrochemical stable window of 0–4.5 V. Moreover, the PVCA-ETPTA layer fabricated by in-situ polymerization helps building an integrated structure, which can significantly reduce the interfacial resistance. The ionic conductivity of LP|PE can reach 1.2 × 10−4 S cm−1 at 55 °C. As a consequence, the assembled NCM622|LP|PE|Li solid state cell shows exceptional electrochemical performance, with 70 % cycle retention for 100 cycles at 0.2 C. • Janus solid electrolyte (JSE) improve electrode/electrolyte interface stability. • The in-situ polymerization Enhance electrolyte/electrolyte interface contact. • JSE improve the electrochemical properties and the cycling performance. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the effect of poly(D, L-lactic acid)10K (PDLLA10K) incorporation on the drug loading and stability of poly(ethylene glycol)2K-block-poly(D, L-lactide)2.4K (mPEG2k-b-PDLLA2.4k) micelles. In addition, a suitable lyophilization protector was screened for this micelle to obtain favorable lyophilized products. Methods: The incorporation ratios of PDLLA10k were screened based on the particle size and drug loading. The dynamic stability, core viscosity, drug release, stability in albumin, and in vivo pharmacokinetic characteristics of PDLLA10k incorporated micelles were compared with the original micelles. In addition, the particle size variation was used as an indicator to screen the most suitable lyophilization protectant for the micelles. DSC, FTIR, XRD were used to illustrate the mechanism of the lyophilized protectants. Results: After the incorporation of 5 wt% PDLLA10K, the maximum loading of mPEG2k-b-PDLLA2.4k micelles for TM-2 was increased from 26 wt% to 32 wt%, and the in vivo half-life was increased by 2.25-fold. Various stability of micelles was improved. Also, the micelles with hydroxypropyl-β-cyclodextrin (HP-β-CD) as lyophilization protectants had minimal variation in particle size. Conclusions: PDLLA10k incorporation can be employed as a strategy to increase the stability of mPEG2k-b-PDLLA2.4k micelles, which can be attributed to the viscosity building effect. HP-β-CD can be used as an effective lyophilization protectant since mPEG and HP-β-CD form the pseudopolyrotaxanesque inclusion complexes. [ABSTRACT FROM AUTHOR]

• Two derivatives of sophorolipids have been prepared. • SL-DMEA and SL-TMEAI have better surface activity. • SL-DMEA and SL-TMEAI can significantly increase the solubility of baicalin. • SL-DMEA and SL-TMEAI can enhance the antioxidant capacity of baicalin. Baicalin is a flavonoid compound extracted from the Scutellaria baicalensis plant. It possesses strong free radical scavenging ability and has a wide range of medical applications in antibacterial, anti-inflammatory, and anti-tumor fields. However, its limited solubility in water restricts its application. In this study, we prepared SL-DMEA by the amidation of acidic sophorolipids and N, N-dimethylethanolamine, while SL-TMEAI was synthesized via the quaternization of SL-DMEA with iodomethane. The structures of SL-DMEA and SL-TMEAI were confirmed by 1H NMR, FT-IR, and Mass spectra. Surface tension and micelle microenvironment indicated that SL-DMEA and SL-TMEAI exhibit superior surface activity. Furthermore, the solubility of baicalin in aqueous solutions containing SL-DMEA and SL-TMEAI was approximately 70 mg/L and 75 mg/L, while it was only 18 mg/L in SL-COOH solution, which were significantly higher than the solubility in pure water (4 mg/L). Similarly, SL-DMEA and SL-TMEAI can enhance the antioxidant activity of baicalin. Specifically, in the SL-TMEAI aqueous solution, the free radical scavenging rate of baicalin was increased by 10 %–20 %. Density functional theory calculations revealed that SL-DMEA and SL-TMEAI formed stable hydrogen bonds with baicalin molecules, which can increase the solubility of baicalin in water and expose the groups that react with free radicals in the solution, thereby enhancing the antioxidant activity. These results demonstrated that SL-DMEA and SL-TMEAI could significantly enhance the solubility and antioxidating of baicalin in water through a hydrotropy mechanism. [ABSTRACT FROM AUTHOR]

Surface passivation is an effective method to prepare compact and uniform perovskite films. With TRZ-X passivation, perovskite film can effectively increase grain size, enhance crystallinity, reduce roughness, extend carrier lifetime, and decrease defect density, contributing to the efficiency and stability of PSCs. Finally, the TRZ-F passivated PSC achieved a best power conversion efficiency of 19.81%. In addition, which maintained 92% of the initial PCE after 1200 h of storage at ambient conditions of 25% relative humidity. [Display omitted] • TRZ-X features 1,3,5-triazine as a core and para -halogenated benzene as a peripheral unit. • The combined action of C = N bonds and halogen atoms can effectively reduce the unsaturated Pb2+ defects in perovskite. • TRZ-X hydrophobic passivation layer could prevent moisture penetration of perovskite films. • The TRZ-F passivated device obtained an improved efficiency of 19.81% and moisture stability. Surface passivation is a practical approach to improve the efficiency and stability of perovskite solar cells (PSCs). In this paper, we introduce para -halogenated triphenyltriazine (TRZ-X, X = F, Br, I) to modify the perovskite absorbers. As the core of TRZ-X, 1,3,5-Triazine has abundant C = N bonds, which can produce intermolecular interactions with uncoordinated Pb2+. The halogen atoms as peripheral unit of TRZ-X with strong electronegativity can not only generate ionic bonds with Pb2+ in the perovskite but also form a stable rigid plane with the TRZ group. Under the synergy effect of C = N bonds and halogen atoms, the defect density of perovskite films is effectively decreased, contributing to the power conversion efficiency (PCE) and stability of devices. Moreover, the presence of TRZ-X hydrophobic passivation layer could prevent moisture penetration, which is beneficial to long-term stability of PSCs. Due to the strong electronegativity, TRZ-F modified device presents the best PCE of 19.81% compared with that (18.32%) of control device. In addition, TRZ-F passivated and unencapsulated device retains 81% of the initial PCE after 1200 h storage under ambient condition with a relative humidity of 70%, whereas the pristine device decays to 59% of the initial PCE under the same conditions. [ABSTRACT FROM AUTHOR]

[Display omitted] • Negatively charged WO 3 self–assembly incorporate with positively charged CsPbBr 3 via electrostatic interaction. • A S–scheme charge transfer pathway is created in CsPbBr 3 /WO 3 heterojunction. • Introducing moderate oxygen vacancies provide more active sites for CO 2 adsorption and activation. • Efficient, long-term and stable CO 2 photoreduction is realized. • MF support could reduce the contamination of toxic Pb2+ leakage to environment. CO 2 photoreduction of CsPbBr 3 is still restricted due to its low conversion efficiency, poor water–resistance, and high toxicity of lead. In this study, three–dimensional porous melamine foam (MF) supported WO 3 /CsPbBr 3 S–scheme heterojunctions with appropriate surface oxygen vacancies are constructed, successfully achieving efficient and long–period CO 2 photoreduction in liquid–phase H 2 O environment. WO 3 rods (R–WO 3) and WO 3 sheets (S–WO 3) are fabricated by controlling the precursor solutions with rich and poor Cl−, respectively, which self–assembly incorporate with CsPbBr 3 to form heterojunctions. A S–scheme charge transfer pathway is created in WO 3 /CsPbBr 3 , which facilitates charge separation and retains strong redox ability of composites simultaneously. S–WO 3 possesses the higher specific surface area and oxygen vacancies concentration than R–WO 3 , contributing to photocatalytic activity. MF/S–WO 3 /CsPbBr 3 exhibites the best CO 2 conversion efficiency, with electron consumption rate of 1720.60 μmol/g/h, which ascribes to the synergy effect of MF support, S–scheme heterojunction and oxygen vacancies. Moreover, MF/S–WO 3 /CsPbBr 3 realizes the long–period CO 2 photoreduction, with no obvious decrease of products yield after eight 8–h cycles of tests. Furthermore, the strong adherence of sample on MF support could reduce the contamination of toxic Pb2+ leakage to environment. [ABSTRACT FROM AUTHOR]

As nitrogen-rich adducts, both 1H-benzimidazole (BIE-H) and 1-(6-bromohexyl)-1H-benzimidazole (BIE-Br) could sufficiently passivate the unsaturated Pb2+ defect of perovskites. Notably, the Br atoms of BIE-Br not only further promote the quality of the perovskite film, but also participate in the lattice restructuring of perovskite, which suppresses the non-radiative recombination of charge carriers, enlarges the band gap of perovskite and improves the energy level match of PSC. Furthermore, the presence of hydrophobic alkyl chains could protect the active layer from moisture erosion. Eventually, the BIE-Br modified PSC delivers a champion efficiency of 20.47% along with excellent operational stability. [Display omitted] • Nitrogen-rich adducts possess the tremendous potential to passivate unsaturated Pb2+ defect in perovskites via Lewis acid-base coordination. • The Br atoms of BIE-Br can not only further passivate the traps in perovskite, but also participate in the lattice restructuring of perovskite. • The presence of hydrophobic alkyl chains could effectively protect the active layer from moisture erosion. • The synergistic modification of benzimidazole and bromohexyl promoted the efficiency and stability of MAPbI 3 -based PSCs. High efficiency and long-term durability are two crucial factors for commercialization application of perovskite solar cells (PSCs). In this paper, we designed and fabricated two organic molecules to modify perovskite films. As nitrogen-rich adducts, both C N and C N groups in 1H-benzimidazole (BIE-H) and 1-(6-bromohexyl)-1H-benzimidazole (BIE-Br) possess the tremendous potential to passivate unsaturated Pb2+ defect of perovskites via Lewis acid-base coordination. The Br atoms of BIE-Br could also passivate uncoordinated Pb2+, improving perovskite film quality and inhibiting non-radiative recombination of charge carriers. Moreover, Br− ions in BIE-Br could participate in the lattice restructuring of perovskite, which enlarges the band gap of perovskite and improves the energy level match of device, contributing to the decrease of energy losses during charge migration. Furthermore, the presence of hydrophobic alkyl chains could protect the active layer from moisture erosion, which enhances the durability of PSCs. As a result, the PCE of BIE-Br modified device reaches to 20.47 %, much higher than those of the control and BIE-H treated PSCs, with efficiencies of 18.98 % and 19.74 %, respectively. The BIE-Br modified device also exhibits the significant long-term stability without any encapsulation, which maintains 78 % of its initial PCE after 600 h storage under ambient conditions. [ABSTRACT FROM AUTHOR]