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The encapsulation efficiency (EE%) reflects the amount of bioactive components that can be loaded into nanoliposomes. Obtaining a suitable nanoliposome stabiliser may be the key to improving their EE%. In this study, three polyphenols were screened as stabilisers of nanoliposomes with high nisin EE%, with curcumin nanoliposomes (Cu-NLs) exhibiting the best performance (EE% = 95.94%). Characterizations of particle size, PDI and zeta potential indicate that the Cu-NLs had good uniformity and stability. TEM found that nisin accumulated at the edges of the Cu-NLs' phospholipid layer. DSC and FT-IR revealed that curcumin was involved in the formation of the phospholipid layer and altered its structure. FT-IR and molecular docking simulations indicate that the interactions between curcumin and nisin are mainly hydrogen bonding and hydrophobic. In whole milk, Cu-NLs effectively protected nisin activity. This study provides an effective strategy for improving the EE% of nanoliposomes loaded with nisin and other bacteriocins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this work, soybean lecithin (LC) was used to modify β-cyclodextrin (β-CD) with hydrophobic fat chains to become amphiphilic (LC-CD), and vitamin E (VE) was encapsulated in former modified β-CD complexes (LC-CD-VE), the new Pickering emulsions stabilized by LC-CD-VE and LC-CD complexes for the delivery of β-carotene (BC) were created. The surface tension, contact angle, zeta potential, and particle size were used to assess the changes in complexes nanoparticles at various pH values. Furthermore, LC-CD-VE has more promise as Pickering emulsion stabilizer than LC-CD because of the smaller particle size (271.11 nm), proper contact angle (58.02°), and lower surface tension (42.49 mN/m). The interactions between β-cyclodextrin, soybean lecithin, and vitamin E were confirmed using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and thermogravimetric analysis (TGA). The durability of Pickering emulsions was examined at various volume fractions of the oil phase and concentrations of nanoparticles. Compared to the emulsion stabilized by LC-CD, the one stabilized by LC-CD-VE showed superior storage stability. Moreover, for the delivery of BC, Pickering emulsions stabilized by LC-CD and LC-CD-VE can outperform bulk oil and Tween 80 stabilized emulsions in terms of UV light stability, storage stability, and bioaccessibility. This work could offer fresh perspectives on stabilizer alternatives for Pickering emulsion delivery systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Coronary artery disease (CAD) is the leading cause of death worldwide. Earlier detection of CAD improves treatment outcomes and secondary prevention. The circulating fetuin-B protein is considered to be a promising biomarker for the early detection of CAD. However, a facile and reliable clinical test for fetuin-B is still lacking. Herein, we describe a reliable fluorescent biosensor for detecting fetuin-B in plasma that combines quantum dots-doped polystyrene nanoparticles with an immunochromatographic assay strip (QNPs-ICAS). The QNPs served as detection signals in the QNPs-ICAS sensor system, which was based on a double-antibody sandwich structure. Under optimum experimental conditions, the biosensor exhibited a broad linear range of 1-200 ng mL -1 and a low detection limit of 0.299 ng mL -1 . Furthermore, the proposed immunosensor demonstrated high sensitivity, satisfactory selectivity, good reproducibility, and excellent recovery. Finally, the performance and applicability of our QNPs-based ICAS system were validated in clinical samples using a commercial ELISA kit with excellent correlations (r = 0.98451, n = 116). To conclude, the proposed sensor served as a rapid, sensitive, and accurate method for detecting fetuin-B in actual clinical samples, thereby demonstrating its potential for preliminary CAD screening and diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Triamcinolone acetonide (TA), a medium-potency synthetic glucocorticoid, is primarily employed to treat posterior ocular diseases using vitreous injection. This study aimed to design novel ocular nanoformulation drug delivery systems using PLGA carriers to overcome the ocular drug delivery barrier and facilitate effective delivery into the ocular tissues after topical administration. The surface of the PLGA nanodelivery system was made hydrophilic (2-HP-β-CD) through an emulsified solvent volatilization method, followed by system characterization. The mechanism of cellular uptake across the corneal epithelial cell barrier used rhodamine B (Rh-B) to prepare fluorescent probes for delivery systems. The triamcinolone acetonide (TA)-loaded nanodelivery system was validated by in vitro release behavior, isolated corneal permeability, and in vivo atrial hydrodynamics. The results indicated that the fluorescent probes, viz., the Rh-B-(2-HP-β-CD)/PLGA NPs and the drug-loaded TA-(2-HP-β-CD)/PLGA NPs, were within 200 nm in size. Moreover, the system was homogeneous and stable. The in vitro transport mechanism across the epithelial barrier showed that the uptake of nanoparticles was time-dependent and that NPs were actively transported across the epithelial barrier. The in vitro release behavior of the TA-loaded nanodelivery systems revealed that (2-HP-β-CD)/PLGA nanoparticles could prolong the drug release time to up to three times longer than the suspensions. The isolated corneal permeability demonstrated that TA-(2-HP-β-CD)/PLGA NPs could extend the precorneal retention time and boost corneal permeability. Thus, they increased the cumulative release per unit area 7.99-fold at 8 h compared to the suspension. The pharmacokinetics within the aqueous humor showed that (2-HP-β-CD)/PLGA nanoparticles could elevate the bioavailability of the drug, and its C max was 51.91 times higher than that of the triamcinolone acetonide aqueous solution. Therefore, (2-HP-β-CD)/PLGA NPs can potentially elevate transmembrane uptake, promote corneal permeability, and improve the bioavailability of drugs inside the aqueous humor. This study provides a foundation for future research on transocular barrier nanoformulations for non-invasive drug delivery.

The food industry has paid lots of attentions to curcumin because of its potential bioactive qualities. However, its use is severely constrained by its low bioavailability, stability and water solubility. Herein, we created sodium caseinate and carboxymethylpachymaran (CMP) nanoparticles (SMCNPs) that were loaded with curcumin. The composite nanoparticles were spherical, as characterized by SEM and TEM, the fluorescence spectroscopy, FTIR and XRD research revealed that hydrogen bonding, hydrophobic interaction and electrostatic interaction were the main drivers behind the creation of the nanoparticles. The SMCNPs exhibited lower particle size, greater dispersion and higher encapsulation rate when the mass ratio of sodium caseinate to CMP was 3:5 (particle size of 166.8 nm, PDI of 0.15, and encapsulation efficiency of 88.07 %). The composite nanoparticles had good antioxidant activity, physical stability and sustained release effect on intestinal tract during the in vitro simulation experiments, successfully preventing the early release of curcumin into gastric fluid. Finally, cytotoxicity studies told that the prepared composite nanoparticles have good biocompatibility and can inhibit the growth of tumor cells (HT-29). In conclusion, using CMP and sodium caseinate as carriers in this study may open up a fresh, environmentally friendly, and long-lasting way to construct a bioactive material delivery system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Luteolin (Lu) is a naturally occurring flavonoid compound with a diverse array of pharmacological activities, including anti-tumor, anti-inflammatory, antibacterial, and neuroprotective properties. However, the therapeutic efficacy and clinical application of Lu are significantly hindered by inherent limitations, such as poor water solubility, short half-life, low bioavailability, and potential off-target toxicity. Recent studies have demonstrated that the utilization of nanocarriers presents a promising strategy to enhance the solubility of Lu, prolong its circulation time, and improve its targeting ability. Despite numerous reviews over the past few decades having focused on the source, pharmacological activities, and molecular mechanisms of Lu, there exists a conspicuous gap in the literature regarding a comprehensive review of Lu-loaded nanoformulations and their applications. To address this gap, we present an exhaustive overview of the advancements and applications of nano-scale drug delivery systems specifically designed for Lu. These platforms encompass micelles, nanocarrier-based systems, emulsified drug delivery systems, and vesicular drug delivery systems. We provide detailed insights into the synthetic materials, preparation methods, physicochemical properties, and significant outcomes associated with these nanoformulations. This systematic review will be particularly valuable to researchers seeking novel avenues in the field of nano-delivery strategies and exploring the potential clinical applications of Lu.

Honokiol (HNK) is a small-molecule polyphenol that has garnered considerable attention due to its diverse pharmacological properties, including antitumor, anti-inflammatory, anti-bacterial, and anti-obesity effects. However, its clinical application is restricted by challenges such as low solubility, poor bioavailability, and rapid metabolism. To overcome these limitations, researchers have developed a variety of nano-formulations for HNK delivery. These nano-formulations offer advantages such as enhanced solubility, improved bioavailability, extended circulation time, and targeted drug delivery. However, existing reviews of HNK primarily focus on its clinical and pharmacological features, leaving a gap in the comprehensive evaluation of HNK delivery systems based on nanotechnology. This paper aims to bridge this gap by comprehensively reviewing different types of nanomaterials used for HNK delivery over the past 15 years. These materials encompass vesicle delivery systems, nanoparticles, polymer micelles, nanogels, and various other nanocarriers. The paper details various HNK nano-delivery strategies and summarizes their latest applications, development prospects, and future challenges. To compile this review, we conducted an extensive search using keywords such as "honokiol", "nanotechnology", and "drug delivery system" on reputable databases, including PubMed, Scopus, and Web of Science, covering the period from 2008 to 2023. Through this search, we identified and selected approximately 90 articles that met our specific criteria., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Yang et al.)

Glioblastoma (GBM) is one of the most aggressive and lethal solid tumors in human. While efficacious therapeutics, such as emerging chimeric antigen receptor (CAR)-T cells and chemotherapeutics, have been developed to treat various cancers, their effectiveness in GBM treatment has been hindered largely by the blood-brain barrier and blood-brain-tumor barriers. Human neutrophils effectively cross physiological barriers and display effector immunity against pathogens but the short lifespan and resistance to genome editing of primary neutrophils have limited their broad application in immunotherapy. Here we genetically engineer human pluripotent stem cells with CRISPR/Cas9-mediated gene knock-in to express various anti-GBM CAR constructs with T-specific CD3ζ or neutrophil-specific γ-signaling domains. CAR-neutrophils with the best anti-tumor activity are produced to specifically and noninvasively deliver and release tumor microenvironment-responsive nanodrugs to target GBM without the need to induce additional inflammation at the tumor sites. This combinatory chemo-immunotherapy exhibits superior and specific anti-GBM activities, reduces off-target drug delivery and prolongs lifespan in female tumor-bearing mice. Together, this biomimetic CAR-neutrophil drug delivery system is a safe, potent and versatile platform for treating GBM and possibly other devastating diseases., (© 2023. The Author(s).)

Cancer stem cells (CSCs), enabled to self-renew, differentiate, and initiate the bulk tumor, are recognized as the culprit of treatment resistance, metastasis, and recurrence. Simultaneously eradicating CSCs and bulk cancer cells is crucial for successful cancer therapy. Herein, we reported that doxorubicin (Dox) and erastin co-loaded hydroxyethyl starch-polycaprolactone nanoparticles (DEPH NPs) eliminated CSCs and cancer cells by regulating redox status. We found that an excellently synergistic effect existed when Dox and erastin were co-delivered by DEPH NPs. Specifically, erastin could deplete intracellular glutathione (GSH), thereby inhibiting the efflux of intracellular Dox and boosting Dox-induced reactive oxygen species (ROS) to amplify redox imbalance and oxidative stress. The high ROS levels restrained CSCs self-renewal via downregulating Hedgehog pathways, promoted CSCs differentiation, and rendered differentiated cancer cells vulnerable to apoptosis. As such, DEPH NPs significantly eliminated not only cancer cells but more importantly CSCs, contributing to suppressed tumor growth, tumor-initiating capacity, and metastasis, in various tumor models of triple negative breast cancer. This study demonstrates that the combination of Dox and erastin is potent in elimination of both cancer cells and CSCs, and that DEPH NPs represent a promising treatment against CSCs-rich solid tumors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Coronary microthromboembolism after acute myocardial infarction (AMI) requires urgent and effective treatment. Early and effective recovery of coronary microcirculation perfusion for the management of AMI would be crucial for better prognosis. Ultrasound assisted thrombolysis in the in-vitro experiments have great potential for the elimination of acute coronary microthromboembolism, especially with stable cavitation using low-intensity focused ultrasound (LIFU) and dodecafluoropentane-loaded acoustic phase-change nanoparticles (DDFP@NPs). Therefore, our study sought to perform animal experiments using this novel treatment method in a porcine model with acute coronary microthromboembolism for further investigation of potential therapeutic values., Methods: Porcine model with acute coronary thromboembolism was established using percutaneous coronary intervention and autologous thrombus injection. For ultrasound assisted thrombolysis, DDFP@NPs were prepared by rotary evaporation and sonication process, and LIFU was optimized. Echocardiography and TTC staining were performed for the evaluation of porcine model establishment and treatment effect., Results: The treatment using LIFU guided DDFP@NPs had almost completely recanalized culprit coronary branch after treatment procedure, and smaller infarcted size (5.4 ± 1.0%), better LVEF (52.5 ± 1.8%) and better coronary microcirculation after 28 days of treatment, which outperformed treatments using LIFU+SonoVue microbubbles (infarcted size: 26.4 ± 3.5% and LVEF: 37.2 ± 3.1%) and LIFU only (infarcted size: 32.2 ± 3.1% and LVEF: 32.2 ± 0.4%) (all P < 0.05), while the treatment effect were similar to treatment using intravenous tissue-plasminogen activator (infarcted size: 4.9 ± 0.9% and LVEF: 53.1 ± 1.1%) (all P > 0.05)., Conclusions: Our study has innovatively established a treatment method using DDFP@NPs combined with LIFU irradiation for coronary thrombolysis and verified its treatment effect with high-efficient thrombolysis in the in-vivo experiments, which can be considered as powerful experimental evident of the novel method for potential clinical use of acute coronary thrombolysis. Multidimensional experimental investigations and cautious verification may need before the method could be used as treatment before preliminary clinical trials., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The application of photodynamic therapy (PDT) is limited by tumor hypoxia. To overcome hypoxia, catalase-like nanozymes are often used to catalyze endogenous H 2 O 2 enriched in tumor tissues to O 2 . Nonetheless, the catalase activity may not be optimal at body temperature and the O 2 supply may not meet the rapid O 2 consumption of PDT. Herein, we provide a two-pronged strategy to alleviate tumor hypoxia based on hollow mesoporous Prussian blue nanoparticles (HMPB NPs). HMPB NPs can efficiently load the photosensitizer chlorin e6 (Ce6) and exhibit photothermal capability and temperature-dependent catalase activity. Under 808 nm laser irradiation, the photothermal effect of HMPB NPs elevated the catalase activity of HMPB NPs for O 2 production. Furthermore, mild hyperthermia reduced cancer associated fibroblasts (CAFs) and induced extracellular matrix (ECM) degradation. The reduction of CAFs and the ECM decreased the solid stress of tumor tissues and normalized the tumor vasculature, which was beneficial for the external supplementation of O 2 to tumors. Thereafter, under 606 nm laser irradiation, Ce6-mediated PDT generated excessive reactive oxygen species (ROS) that induced tumor cell apoptosis and achieved a high tumor inhibition rate of 92.2% in 4T1 breast tumors. Our work indicated that the alleviation of tumor hypoxia from both internal and external pathways significantly enhanced Ce6-mediated PDT against breast cancers.

Antibiotic tolerance and resistance in bacteria have caused a great threat to humankind. Bacteria can rapidly accumulate alarmone nucleotides (guanosine tetra- and pentaphosphate, usually denoted as (p)ppGpp) to repair damaged DNA under adverse conditions. The inhibition synthetase enzyme activity of (p)ppGpp, indirectly preventing synthesis, or promoting degradation, has been reported; however, transferring these strategies to practical applications is still a challenging task due to the lack of highly effective molecules for these purposes. Here, an approach based on molecularly imprinted polymer nanoparticles (MIP-NPs) as antibiotic adjuvants was proposed, where MIP-NPs with specific recognition sites were used to capture alarmone nucleotides released by bacteria during stringent response activation. Enhanced inhibition rates of 40-80% were achieved in the presence of the MIP-NPs. The dose of antibiotic could be greatly reduced by utilizing the MIP-NPs as adjuvants for a similar deactivation effectiveness. Good biocompatibility (no obvious hemolysis or cytotoxic effects) and apparent antimicrobial efficiency for resisting wound infection in vivo support the fact that well-designed MIP-NPs have a bright future in dealing with the growing threat of antibiotic tolerance and resistance.

A novel strategy for sensing protein was proposed through combining the high selectivity of molecular imprinting technology with the excellent upconversion fluorescence of upconversion nanoparticles (UCNPs) and high specific surface area of metal-organic frameworks (MOFs). Herein, the UCNPs acted as signal reporter and MOFs were introduced to increase the rate of mass transfer. The UCNPs@MIL-100 as support material was prepared via a step-by-step method. The imprinted material-coated UCNPs@MIL-100 (UCNPs@MIL-100@MIPs) were obtained by sol-gel technique. The results showed that as the increase of the template protein concentration, the fluorescence intensity of UCNPs@MIL-100@MIPs quenched gradually, and the imprinting factor was 2.90. The linear in the range of 1.00 to 8.00 μM, and the detection limit was 0.59 μM. Therefore, the novel optosensing material is very promising for future applications., (Copyright © 2022. Published by Elsevier B.V.)

Lung cancer remains one of the leading causes of death in humans. Gefitinib is an inhibitor of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) commonly used to suppress tumour growth. However, constantly use of gefitinib results in drug-resistance, reduced efficacy and undesired side effects. To circumvent these drawbacks, targeted and photothermal therapies have emerged as effective strategies. Herein, we are first to adopt a black phosphorus (BP) nanoparticle-based novel delivering strategy by combining gefitinib and cancer cytomembrane to treat non-small cell lung cancer (NSCLC). In these gefitinib-containing nano-carriers, cyanine 5 (Cy5) biotin-labelled BP was incorporated with cancer membrane and then consists of a nanomaterial (BPGM), which enabled to deliver gefitinib to the tumours effectively. The combination of BPGM showed reinforcing effects to suppress NSCLC cells and xenograft tumours without apparent adverse effects both in vitro and in vivo . BPGM facilitated the delivery of gefitinib to tumour tissue and extended its retention time within tumours. These studies thus suggest that BP may serve as novel delivery strategy for lung cancer.

Cancer is one of the main diseases threatening human health. Immunotherapy, in which cancer is treated by activating immune cells and inducing the body's immune response, has rapidly developed. Photothermal therapy (PTT), a new treatment method that ablates tumors by light irradiation, has attracted great attention for its good therapeutic effect and low toxic side effects. In the present study, we combined photothermal and immunotherapy to design a novel nanoparticle delivery system by loading indoleamine 2,3-dioxygenase (IDO) inhibitors and toll-like receptor (TLR) agonists into polydopamine (PDA) nanoparticles coated with polyethylene imine (PEI). This delivery system has the advantages of high homogeneity, good stability, excellent biocompatibility, and low toxicity. In vitro antitumor studies showed that the system effectively inhibited the proliferation of mouse breast carcinoma cells and induced cell apoptosis. From the in vivo studies, we found that the system inhibited the growth of mouse breast carcinoma, facilitated the maturation of antigen-presenting cells, promoted T lymphocyte differentiation, and induced the body's immune response. The present study developed a dual functional drug delivery system combining photothermal therapy and immunotherapy to efficiently improve antitumor therapy with potential clinical application.

The high glutathione (GSH) content in tumor cells strongly affects the efficiency of chemodynamic therapy (CDT). Despite devoted efforts, it still remains a formidable challenge for manufacturing a tumor-specific CDT with rapid and thorough depletion of GSH. Herein, a multistage GSH-consuming and tumor-specific CDT is presented. By consuming the reserved GSH and inhibiting both the raw materials and energy supply of GSH synthesis in cancer cells, it achieves highly potent GSH exhaustion. Our used glycolysis inhibitor cuts off the specific glycolysis of tumor cells to increase the sensitivity to CDT. Furthermore, the starvation effect of glycolysis inhibitor can stimulate the protective mode of normal cells. Since the glycolysis inhibitor and nanocarrier are responsive to tumor microenvironment, this makes CDT more selective to tumor cells. Our work not only fabricates nanomedicine with GSH exhausted function for highly potent CDT but also uses metabolic differences to achieve tumor-specific therapy.

Cancer stem cells (CSCs), also known as tumor initiating cells or tumor repopulating cells, which comprise only a small fraction of tumor, have received tremendous attention during the past two decades, as they are considered as the ringleader for initiation and progression of tumors, therapy resistance, metastasis, and recurrence in the clinic. Hence, eradicating CSCs is critical for successful cancer treatment. To that end, various CSC-targeting therapeutic agents have been pursued. However, these CSC-specific drugs are ineffective toward bulk cancer cells. Furthermore, these anti-CSC drugs not only eradicate CSCs but also affect conventional stem cells in normal organs or tissues. By virtue of the enhanced permeability and retention (EPR) effect, nanomaterial drug delivery systems (NDDSs) passively accumulate in tumor tissues, thereby alleviating severe side effects toward normal viscera. NDDSs can be further functionalized with CSC-specific binding molecules to promote targeted drug delivery toward CSCs. Moreover, NDDSs have unique advantages in encapsulating CSC-specific drugs and cytotoxic agents, realizing synchronized killing of CSCs and bulk cancer cells both temporally and spatially. For these reasons, leveraging nanotherapeutic strategies to target CSCs has gained tremendous attention recently.Some ten years ago, we summarized five basic features of efficient nanotherapeutics (the five features principle), which consist of long circulation, tumor accumulation, deep penetration, cellular internalization, and drug release. Based on this design rationale, we constructed several NDDSs, including nanogels with adaptive hydrophobicity, CSC-derived microparticles with tailored softness, and tumor exosome sheathed porous silicon biomimetic nanoparticles, for targeted drug delivery to tumor. To our astonishment, these NDDSs that possess the five basic features achieve decent drug delivery efficiency toward not only bulk tumor cells but more importantly CSCs. Consequently, such nanotherapeutics as-designed based on the five features principle are potent in eradicating CSCs, even with only cytotoxic drugs, for instance, doxorubicin. Furthermore, commercialized nanomedicines, such as Doxil and Abraxane, can be endowed with these five basic features by hyperbaric oxygen therapy and therefore achieve outstanding drug delivery efficiency, potent CSC elimination, and efficient cancer therapy. These studies suggest that intractable CSCs can be tackled with a material-based approach, highlight the critical role of the five features principle in designing effective nanotherapeutics, and pinpoint the significance of drug delivery efficiency in eliminating CSCs and bulk cancer cells.

Rationale: Chemodynamic therapy (CDT) is an emerging tumor-specific therapeutic strategy. However, the anticancer activity of CDT is impeded by the insufficient Fenton catalytic efficiency and the high concentration of glutathione (GSH) in the tumor cells. Also, it is challenging to eliminate tumors with CDT alone. Thus, simple strategies aimed at constructing well-designed nanomedicines that can improve therapeutic efficiency of CDT and simultaneously incorporate extra therapeutic modes as helper are meaningful and highly required. Method: Tailored to specific features of tumor microenvironment (TME), in this study, we developed a biosafe, stable and TME-activated theranostic nanoplatform (P(HSD-Cu-DA)) for photoacoustic imaging (PAI) and self-amplified cooperative therapy. This intelligent nanoplatform was fabricated following a simple one-pot coordination and polymerization strategy by using dopamine and Cu 2+ as precursors and redox-responsive hydroxyethyl starch prodrugs (HES-SS-DOX) as stabilizer. Results: Interestingly, the pre-doped Cu 2+ in polydopamine (PDA) framework can endow P(HSD-Cu-DA) NPs with tumor-specific CDT ability and remarkably enhance NIR absorption of PDA. PAI and biodistribution tests proved such nanoplatform can effectively accumulate in tumor tissues. Following enrichment, massive amounts of toxic hydroxyl radicals (·OH, for CDT) and free DOX (for chemotherapy) were generated by the stimulation of TME, which was further boosted by local hyperthermia. Concomitantly, in the process of activating these therapeutic functions, GSH depletion triggered by disulfide bond (-SS-) breakage and Cu 2+ reduction within tumor cells occurred, further amplifying intratumoral oxidative stress. Importantly, the framework structure dominated by bioinspired polydopamine and clinical-used HES guaranteed the long-term biosafety of in vivo treatment. As a result, the mutual promotion among different components yields a potent tumor suppression outcome and minimized systemic toxicity, with one dosage of drug administration and laser irradiation, respectively. Conclusion : This work provides novel insights into designing efficient and tumor-specific activatable nanotherapeutics with significant clinical translational potential for cancer therapy., Competing Interests: Competing Interests: The authors (Z. Li, X. Yang, and Y. Xiong) have applied for patents related to this study., (© The author(s).)

Photothermal therapy is promising for augmenting cancer therapeutic outcomes in cancer treatment. Diketopyrrolopyrrole (DPP)-conjugated polymer nanoparticles are in focus due to their dual photoacoustic imaging and photothermal therapy functions. Herein, the design and synthesis of three near-infrared absorbing conjugated polymers, named DPP-SO, DPP-SS and DPP-SSe, with heteroatom substitution of the thiophene moiety were developed for a photoacoustic imaging guided photothermal therapy. It was demonstrated that systematically changing only the heteroatom from O to S or Se could apparently adjust the absorption spectrum and energy gap of DPP-conjugated polymers to obtain the most suitable photothermal transduction agents (PTAs) for use in biomedicine. The characterization of photophysical properties proved that the photothermal conversion efficiency and absorption coefficient of DPP-SO nanoparticles under 808 nm irradiation was up to 79.3% and 66.51 L g -1 cm -1 , respectively, which were much higher than those of DPP-SS and DPP-SSe nanoparticles. Remarkably, the IC 50 value of DPP-SO for killing A549 cells was half that of DPP-SS and DPP-SSe nanoparticles. Further in vivo works demonstrated efficient photothermal therapeutic effects of DPP-SO nanoparticles with the guidance of photoacoustic imaging. Thus, this is an efficient method to regulate the photothermal performance of DPP-conjugated polymers by changing the heteroatom in the molecular skeleton.

Metal-organic frameworks (MOFs) have sparked increasing interest in mimicking the structure and function of natural enzymes. However, their catalytic and therapeutic efficiency are unsatisfactory due to the relatively lower catalytic activity. Herein, inspired by nature, a MOF@COF nanozyme has been designed as a high-efficiency peroxidase mimic, with the metallic nodes of MOFs as active centres, the hierarchical nanocavities produced by the growth of covalent organic frameworks (COFs) as binding pockets to form tailored pore microenvironment around active sites for enriching and activating substrate molecules, to perform enhanced bacterial inhibition. Furthermore, the pseudopodia-like surface of the COFs "skin" enabled the system to catch the bacteria effectively for further amplifying the therapeutic efficiency of MOF-based nanozyme. We believe that the present study will not only facilitate the design of novel nanozymes, but also broaden the biological usage of MOF/COF-based hybrid materials., (© 2020 Wiley-VCH GmbH.)

Macrophages are known to penetrate tumor central hypoxic areas and hold great potential in cancer drug delivery. However, it remains a big challenge for current macrophage-based drug delivery systems (MDDSs) to prevent premature drug leakage and sufficiently release the therapeutics in tumor sites. Moreover, these MDDSs would encounter drug resistance and a hypoxic microenvironment in solid tumors, which further compromised their therapeutic efficacy. Herein, by internalizing a smart nanoparticle (doxorubicin (DOX)-loaded mesoporous carbon nanosphere wrapped with MnO 2 shell) into macrophages, a macrophage vehicle (MMDM) is developed for enhanced chemo/chemodynamic synergistic therapy. The resulting MMDM could avoid premature drug leakage-induced cell dysfunction and maximally maintain cell viability. After accumulating in tumor tissues, the MMDM could be destroyed under a near-infrared laser to sufficiently release the nanoparticle out of the carrier macrophages. The released nanoparticle could then decompose H 2 O 2 to generate O 2 in the tumor microenvironment to relieve tumor hypoxia. Meanwhile, the MnO 2 shell of the nanoparticle is reduced to Mn 2+ by intracellular glutathione, triggering the release of DOX and subsequently resulting in an enhanced Mn 2+ -mediated Fenton-like reaction. This study provides an intriguing strategy to macrophage-based delivery systems for enhanced chemo/chemodynamic synergistic therapy.

Background: There is growing public awareness regarding the health effects of indoor nanoscale particulate matter (INPM) since people spend the majority of their time indoors. INPM could have a direct entry route into the brain via the axons of the olfactory nerve and migrating across the blood-brain barrier (BBB). Using animals to explore this possibility is not a reliable method to fully demonstrate human physiological responses. We, therefore, set out to develop a human 3D functional blood-brain barrier model to examine the potential effects of INPM on the cerebral nervous system., Methods: Human astrocytes were co-cultured and human umbilical vein endothelial cells in 3D within a microfluidic chip to simulate the micro-complex physiological structure of the human BBB. This 3D human organotypic model has then been made to investigate any INPM-induced BBB dysfunction linked to potential cellular responses., Results: A 3D human functional blood-brain barrier was constructed in this study. We observed the translocation of INPM across the blood-brain barrier. The 3D human organotypic chip initially reflected damage to the nervous system with abnormal astrocyte proliferation and a decline in cell viability. We also looked at the behavior of oxidative stress-related biomarkers (ROS, GSH-Px, and MDA). INPM was implicated in aggravating inflammation via reactive oxygen species (ROS). The Keap1-Nrf2-ARE pathway is a key mechanism in cellular resistance to oxidative stress by mediating and activating a variety of antioxidant and detoxification enzymes. Following ROS accumulation, INPM induced abnormal expression of nuclear transcription factor Nrf2. This behavior disturbed the expression of, γ-glutamate synthase (γ-GCS) and heme oxygenase (HO-1), which further exacerbated the imbalance of the antioxidant system., Conclusions: This functional 3D human organotypic chip effectively mimics the physiological response of the human BBB. The chip provides a micro-complex structure to simulate the internal environment of the human blood-brain barrier, and partially simulates the physiological responses of the BBB to INPM exposure. Based on this model, INPM was shown to affect the blood-brain barrier biofunction by disrupting the Keap1-Nrf2-ARE pathways., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A fluorometric method based on molecularly imprinted upconversion fluorescence test strip was developed for the determination of tyramine. It exploited the green fluorescence of upconversion nanoparticles (UCNPs) and the specific recognition property of molecularly imprinted polymers (MIPs). UCNPs were attached to filter paper with glue, and MIPs were prepared via in situ polymerization on the surface of UCNPs by using tyramine as template, methacrylic acid as functional monomer, and ethylene glycol dimethacrylate as cross-linker. The green fluorescence of the test strip, with excitation/emission wavelength 980/550 nm, was enhanced by tyramine. The test strip was suitable for the determination of tyramine in the linear range 1.0-100.0 mg L -1 , and a relatively low limit of detection (0.2 mg L -1 ) was achieved. The test strip also worked well for the quantitation of tyramine in spiked red wine and mature vinegar. Recoveries are ranged from 84.9 to 99.9%. The relative standard deviations are below 5.6%. Graphical abstract.

Interfacial self-assembly has become a powerful force for regulating the amphipathy of Pickering emulsions on the oil/water interface. Herein, metal-phenolic supramolecular coatings, acting as a regulator on the oil/water interface, were fabricated on the surface of zein nanoparticles (NPs), as a consequence of which the prepared Pickering emulsions stabilized by the decorated zein NPs exhibited diverse properties, decided by different concentrations of zein, tannic acid (TA), and metal ions (Fe 3+ ). Metal-phenolic network-decorated zein NPs named ZTFe x NPs (ZTFe NPs represented zein/TA/Fe 3+ NPs, and x represented different concentrations of compounds) exhibited increasing diameters of 100-110 nm. Three-phase contact angles also showed that the strong hydrophobicity of zein NPs could be decreased as a result of the formation of metal-phenolic networks. As for corresponding Pickering emulsions, the covering of TA-Fe 3+ networks on zein NPs could enhance the stability of zein NP-based emulsion obviously, which might be due to the fact that ZTFe x NPs revealed the ability to form strong films on the oil/water interfaces. ZTFe4 was selected as an optimal concentration because of its minimum size and excellent storage stability. Besides, it was also found that the diameter of ZTFe4-based emulsion enhanced with the increase in the oil phase. The rheological measurement results showed that both G ' and G ″ increased with the increase of x and the oil phase. In general, our paper not only highlighted a straightforward method for the interfacial nanofabrication of solid particles but also provided a novel and potential strategy in Pickering emulsion applications.

Thionated perylenediimides (PDIs) can potentially generate thermal and reactive oxygen species and thus can be used as theranostic agents for photothermal/photodynamic therapy. Herein, thionated cis-/trans-isomer PDI-CS and PDI-TS were designed and prepared to investigate thionation engineering on therapeutic performance. The results revealed that the photodynamic performance is less associated with the positon of sulfur atoms. By contrast, trans-isomer PDI-TS showed a photothermal conversion efficiency of up to 58.4%, which was 40% higher than that of PDI-CS (∼41.6%). An in vitro half-maximal inhibitory concentration of ∼7.78 μg mL-1 was achieved for PDI-TS, which was 1.7-fold smaller than that of PDI-CS, strongly reasserting the regioisomer-modulated phototheranostic performance. Notably, the strong π-π and CS interactions in PDI-TS nanoagents are essential factors attributed to their excellent photothermal performance, indicating that the optimization of non-bonding interactions is an ingenious way to improve phototheranostic performance. This work provides a facile means of creating thio-perylenediimides that possess excellent antitumor properties and a novel proof of concept to improve therapeutic performance through the optimization of non-bonding interactions.

The insufficient intracellular H 2 O 2 level in tumor cells is closely associated with the limited efficacy of chemodynamic therapy (CDT). Despite tremendous efforts, engineering CDT agents with a straightforward and secure H 2 O 2 supplying ability remains a great challenge. Inspired by the balance of H 2 O 2 generation and elimination in cancer cells, herein, a nanozyme-based H 2 O 2 homeostasis disruptor is fabricated to elevate the intracellular H 2 O 2 level through facilitating H 2 O 2 production and restraining H 2 O 2 elimination for enhanced CDT. In the formulation, the disruptor with superoxide dismutase-mimicking activity can convert O 2 •- to H 2 O 2 , promoting the production of H 2 O 2 . Simultaneously, the suppression of catalase activity and depletion of glutathione by the disruptor weaken the transformation of H 2 O 2 to H 2 O. Thus, the well-defined system could perturb the H 2 O 2 balance and give rise to the accumulation of H 2 O 2 in cancer cells. The raised H 2 O 2 level would ultimately amplify the Fenton-like reaction-based CDT efficiency. Our work not only paves a way to engineer alternative CDT agents with a H 2 O 2 supplying ability for intensive CDT but also provides new insights into the construction of bioinspired materials.

Background: The identification of foodborne pathogenic bacteria types plays a crucial role in food safety and public health. In consideration of long culturing times, tedious operations and the desired specific recognition elements in conventional methods, the alternative fluorescent sensor arrays can offer a high-effective approach in bacterial identification by using multiple cross-reactive receptors. Herein, we achieve this goal by constructing an upconversion fluorescent sensor array based on anti-stokes luminogens featuring a series of functional lanthanide-doped upconversion nanoparticles (UCNPs) with phenylboronic acid, phosphate groups, or imidazole ionic liquid. The prevalent spotlight effect of microorganism and the electrostatic interaction between UCNPs and bacteria endow such sensor array an excellent discrimination property., Results: Seven common foodborne pathogenic bacteria including two Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes) and five Gram-negative bacteria (Escherichia coli, Salmonella, Cronobacter sakazakii, Shigella flexneri and Vibrio parahaemolyticus) are precisely identified with 100% accuracy via linear discriminant analysis (LDA). Furthermore, blends of bacteria have been identified accurately. Bacteria in real samples (tap water, milk and beef) have been effectively discriminated with 92.1% accuracy., Conclusions: Current fluorescence sensor array is a powerful tool for high-throughput bacteria identification, which overcomes the time-consuming bacteria culture and heavy dependence of specific recognition elements. The high efficiency of whole bacterial cell detection and the discrimination capability of life and death bacteria can brighten the application of fluorescence sensor array.

Ag + and SCN - play extremely important roles in the fields of the physiology and environment. In this work, on the basis of phenanthro[9,10-d]imidazole derivative (DIPIP) which can exhibit the aggregation-induced emission (AIE) properties in aqueous solution, we achieved a sequential on-off-on switch for Ag + and SCN - with high selectivity and sensitivity. A remarkable fluorescence quenching effect of Ag + on the probe DIPIP was observed with 1:2 stoichiometry, Subsequently, the fluorescence intensity of in situ generated DIPIP-Ag + ensemble was easily switched on after the interaction between Ag + and SCN - , which was attributed to the stronger affinity of SCN - to capture Ag + . In particular, the extreme limits of detection (LOD) for Ag + and SCN - in standard solutions were as low as to be 74.5 nM and 7.8 nM, respectively. Furthermore, the probe DIPIP and the DIPIP-Ag + ensemble could be used to detect Ag + in the real water and SCN - in smoker saliva samples, respectively. In addition, the sequential "on-off-on" fluorescence mode of DIPIP to Ag + and SCN - were also successfully applied in living HeLa cells., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Development of high-performance photoactive agents with tumor-specific capability for effective nanotherapeutics has received much attention in the past decades. Herein, we report a nanotherapeutic based on bis-diketopyrrolopyrrole (BDPP) conjugated polymer nanoparticles (PBDPP NPs) with remarkable near-infrared (NIR) absorption at 808 nm and high photothermal energy conversion efficiency up to 60%. In particular, precise glioblastoma-specific capability and killing ability for glioblastoma cells were effectively achieved in vitro by treating with only PBDPP NPs to induce cell apoptosis or by interaction with PBDPP NPs under NIR laser irradiation to trigger cell necrosis. Impressively, a half-maximal inhibitory concentration as low as of ∼0.15 μg mL -1 was achieved, and the magnitude is 5 to 4.4 × 10 4 -fold lower than those of reported agents. In vivo experiment with mice further shows that the PBDPP NPs show good efficacy of photothermal therapy and complete tumor elimination using a record-low dosage of 0.35 mg mL -1 under 808 nm irradiation of low power (0.5 W cm -2 ). This study thus demonstrates a promising strategy of low-dose, high-efficacy polymer-based nanoagonist for specific phototherapy of glioblastoma., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Herein, a promising carrier, graphene oxide (GO) decorated with ZnO nanoparticles, denoted as GO/ZnO composite, has been designed and constructed. This carrier was characterized by X-ray powder diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy and thermogravimetry. Then, Candida rugosa lipase (CRL) was immobilized onto the GO-based materials via physical adsorption. Our results indicated that the lipase loading amount on the GO/ZnO composites was about 73.52 mg of protein per g. In the activity assay, the novel immobilized lipase GO/ZnO@CRL, exhibited particularly excellent performance in terms of thermostability and reusability. Within 30 min at 50 °C, the free lipase, GO@CRL and ZnO@CRL had respectively lost 64%, 62% and 41% of their initial activity. However, GO/ZnO@CRL still retained its activity of 63% after 180 min at 50 °C. After reuse of the GO/ZnO@CRL 14 times, 90% of the initial activity can be recovered. Meanwhile, the relative activity of GO@CRL and ZnO@CRL was 28% and 23% under uniform conditions. Hence, GO-decorated ZnO nanoparticles may possess great potential as carriers for immobilizing lipase in a wide range of applications., Competing Interests: The authors declare no conflict of interest.

While a diamond-like carbon (DLC)-coated joint prosthesis represents the implant of choice for total hip replacement in patients, it also leads to concern due to the cytotoxicity of wear debris in the form of graphite nanoparticles (GNs), ultimately limiting its clinical use. In this study, the cytotoxicity of various GN doses was evaluated. Mouse macrophages and osteoblasts were incubated with GNs (<30 nm diameter), followed by evaluation of cytotoxicity by means of assessing inflammatory cytokines, results of alkaline phosphatase assays, and related signaling protein expression. Cytotoxicity evaluation showed that cell viability decreased in a dose-dependent manner (10-100 μg ml -1 ), and steeply declined at GNs concentrations greater than 30 μg ml -1 . Noticeable cytotoxicity was observed as the GN dose exceeded this threshold due to upregulated receptor of activator of nuclear factor kB-ligand expression and downregulated osteoprotegerin expression. Meanwhile, activated macrophage morphology was observed as a result of the intense inflammatory response caused by the high doses of GNs (>30 μg ml -1 ), as observed by the increased release of TNF-α and IL-6. The results suggest that GNs had a significant dose-dependent cytotoxicity in vitro, with a lethal dose of 30 μg ml -1 leading to dramatic increases in cytotoxicity. Our GN cytotoxicity evaluation indicates a safe level for wear debris-related arthropathy and could propel the clinical application of DLC-coated total hip prostheses.

A novel strategy was developed to prepare double responsive smart upconversion fluorescence material for highly specific enrichment and sensing of glycoprotein. The novel double responsive smart sensing material was synthesized by choosing Horse radish peroxidase (HRP) as modal protein, the grapheme oxide (GO) as support material, upconversion nanoparticles (UCNPs) as fluorescence signal reporter, N-isopropyl acrylamide (NIPAAM) and 4-vinylphenylboronic acid (VPBA) as functional monomers. The structure and component of smart sensing material was investigated by transmission electron microscopy (TEM), Scanning electron microscopy (SEM), X-ray photoelectron spectroscopic (XPS) and Fourier transform infrared (FTIR), respectively. These results illustrated the smart sensing material was prepared successfully. The recognition characterizations of smart sensing material were evaluated, and results showed that the fluorescence intensity of smart sensing material was reduced gradually, as the concentration of protein increased, and the smart sensing material showed selective recognition for HRP among other proteins. Furthermore, the recognition ability of the smart sensing material for glycoprotein was regulated by controlling the pH value and temperature. Therefore, this strategy opens up new way to construct smart material for detection of glycoprotein., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A novel method combined the high selectivity of molecular imprinting technology with the strong fluorescence property of upconversion nanoparticles (UCNPs) for sensing of Cytochrome c (Cyt c) was proposed. The molecularly imprinted material-coated upconversion nanoparticles (UCNPs@MIP) were obtained by in situ coating Cyt c imprinted materials to the surface of the carboxyl modified UCNPs through sol-gel technique. The structure and component of the prepared UCNPs@MIP was investigated by transmission electron microscopy (TEM), power X-ray diffraction (XRD), energy-dispersive X-ray analysis (EDXA) and X-ray photoelectron spectroscopic (XPS). The TEM showed the diameter of UCNPs was 40 nm, and thickness of MIP was 5-10nm. The fluorescence intensity of UCNPs@MIP reduced gradually with the increase of Cyt c concentration. Under optimum conditions, the imprinting factor is 3.19, and the UCNPs@MIP showed selective recognition for Cyt c among other proteins such as bovine serum albumin (BSA) and Lysozyme (Lyz). Therefore, this new method for sensing protein is very promising for future applications., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In this work, a new cellulose derivative, octadecyl modified quaternized cellulose (ODMQC), was synthesized and used as additive in the background electrolyte for capillary electrophoresis. The derivative bearing hydrophobic groups and hydrophilic groups can self-assemble into a stable nano-scaled micelle structure in aqueous solution. When ODMQC was added in running buffer, the capillaries were shown to generate applicable anodal EOF over the investigated range of pH 3.0-12.0. Due to the lack of UV active groups, the ODMQC did not disturb the UV detection. It is shown that ODMQC-added capillaries allow the separation of basic proteins by reducing their adsorption onto the capillary wall. Also, the addition of ODMQC provides adequate separation of aromatic acids with low pKa values and improved separation of sulfa drugs. Moreover, it is demonstrated that the addition of ODMQC can incorporate an additional reversed-phase mechanism that improves the separation of neutral analytes., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Stimuli-responsive drug delivery systems are highly desirable for improved therapeutic efficacy and minimized adverse effects of drugs. Mesoporous silica nanoparticles (MSNs) functionalized with pentadentate ligands, N-(3-trimethoxysilylpropyl)ethylenediamine triacetate (TSP-DATA), in the presence of metal ions with and without myoglobin (Mb)-containing surface-accessible histidine residues, were constructed for pH-triggered controlled release. The DATA ligands immobilized on the MSN pore outlets could encapsulate cargo within the pores by metal latching across pore openings, and release efficiency increased with the increase of surface density of the DATA ligands. The release efficiencies for the metal-chelating protein nanogates, through multiple-site binding of Mb with the metal-chelating ligands, were higher than those for the metal-latching ligand nanogates but were almost independent of surface density of the ligands investigated. Both the metal-latching ligands and the metal-chelating proteins played a synergetic role in gating MSNs for high-loading drug delivery and stimuli-responsive controlled release. The constructed Mb-Cu(2+)-gated MSN delivery system has promising applications in targeted drug therapy of tumors.

A novel biological method for the synthesis of platinum nanoparticles using the horse spleen apoferritin (HSAF) is reported. When HSAF was incubated with K(2)PtCl(6) at 23 degrees C) for 48 h followed by subsequent reduction with NaBH(4) it resulted in the formation of spherical platinum nanoparticles, size 4.7 +/- 0.9 nm, with narrow particle size distribution confirmed by transmission electron microscopy and energy dispersive X-ray analysis. As the initial platinum concentration increased through 0.155, 0.31, 0.465 to 0.62 mM the efficiency of its removal from solution by the apoferritin was 99, 99, 84 and 71% respectively. The maximum uptake of platinum salt per mM apoferritin was estimated at 12.7 mmol l(-1) h(-1). These results clearly indicate that the HSAF protein cage can successfully serve as a suitable size-constrained support matrix for the biological synthesis of platinum nanoparticles.

High-performance carbon nanotubes-supported catalysts (/CNTs) catalysts were prepared on the basis of precursors reduced by hydrogen plasma (/CNTs-HP) generated by microwave. The other two /CNTs catalysts prepared by hydrogen (/CNTs-) and 4 (/CNTs-) reduction were also involved for comparison. The practical composition of the catalysts was characterized with energy dispersive analysis of X-ray (EDAX). It was shown from transmission electron microscopy (TEM) and X-ray diffraction (XRD) that the nanoparticles in /CNTs-HP were uniformly dispersed on CNTs with smaller particle size around 2 nm and narrower size distribution as compared with the other two catalysts. Additionally, X-ray photoelectron spectrum (XPS) analysis indicated higher amount of zero-valence states of in /CNTs-HP caused by hydrogen plasma treatment. The electrooxidation of liquid methanol on these catalysts was investigated by cyclic voltammetry (CV), linear sweep voltammetry (LSV) and chronoamperometry. The long-time durability is very comparable to all the three catalysts. Remarkably, the /CNTs-HP possessed the highest electrocatalytic activity, suggesting that the hydrogen plasma reduction approach can be a promising reduction method for preparing high-performance -based electrocatalysts. The electrochemical performance of the Pt/CNTs-HP catalysts prepared by hydrogen plasma were tested for methanol oxidation. The as-prepared catalysts showed the highest current density toward methanol oxidation reaction. This significant improvement in the catalytic performance was attributed to the high dispersion level of Pt particles and the small particle size. [ABSTRACT FROM AUTHOR]