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In recent decades, protein-based therapy has garnered valid attention for treating infectious diseases, genetic disorders, cancer, and other clinical requirements. However, preserving protein-based drugs against degradation and denaturation during processing, storage, and delivery poses a formidable challenge. Herein, we designed a novel fluoroamphiphiles polymer to deliver protein. Two different formulations of nanoparticles, cross-linked (CNP) and micelle (MNP) polymer, were prepared rationally by disulfide cross-linked and thin-film hydration techniques, respectively. The size, zeta potential, and morphology of both formulations were characterized and the delivery efficacy of both in vitro and in vivo was also assessed. The in vitro findings demonstrated that both formulations effectively facilitated protein delivery into various cell lines. Moreover, in vivo experiments revealed that intramuscular administration of the two formulations loaded with a SARS-CoV-2 recombinant receptor-binding domain (RBD) vaccine induced robust antibody responses in mice without adding another adjuvant. These results highlight the potential use of our carrier system as a safe and effective platform for the in vivo delivery of subunit vaccines., 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.)

Background: Viral pneumonia, a pressing global health issue, necessitates innovative therapeutic approaches. Acyclovir, a potent ring-opening antiviral agent with broad-spectrum activity, faces water solubility, oral bioavailability, and drug resistance challenges. The aim of this study was to increase the efficacy of acyclovir through respiratory delivery by encapsulating it within albumin-modified lipid nanoparticles and formulate it as a spray., Methods: Nanoparticles was synthesized via the reverse evaporation method; its physicochemical characteristics were rigorously evaluated, including particle size, zeta potential, morphology, encapsulation efficiency, drug loading, and release profile. Furthermore, the cytotoxicity of nanoparticles and its therapeutic potential against viral pneumonia were assessed through cellular and animal model experiments. Result s: Nanoparticles exhibited a spherical morphology, with a mean particle size of 97.48 ± 5.36 nm and a zeta potential of 30.28 ± 4.72 mv; they demonstrated high encapsulation efficiency (93.26 ± 3.27%), drug loading (11.36 ± 0.48%), and a sustained release profile of up to 92% under neutral conditions. Notably, nanoparticles showed low cytotoxicity and efficient intracellular delivery of acyclovir. In vitro studies revealed that nanoparticles significantly reduced interleukin-6 levels induced by influenza virus stimulation. In vivo , nanoparticles treatment markedly decreased mortality, attenuated the inflammatory markers interleukin-6 and tumor necrosis factor-α levels, and mitigated inflammatory lung injury in mice with viral pneumonia., Conclusions: In this study, albumin was modified with polyethylene glycol (PEG) containing cationic lipid nanoparticles (LN) to prepare albumin-modified lipid nanoparticles encapsulating acyclovir (ALN-Acy), which can effectively deliver Acy into tissues and cells, prolong the survival of mice, and reduce lung injury and inflammatory factors. White albumin LN can be used as efficient drug delivery carriers, and the delivery of Acy via albumin LN is expected to be a therapeutic strategy for treating inflammatory diseases., (© 2024 The Author(s). Published by IMR Press.)

Atherosclerosis is a persistent inflammatory condition of the blood vessels associated with abnormalities in lipid metabolism. Development of biomimetic nanoplatforms provides an effective strategy. Herein, inspired by the peptide CLIKKPF spontaneously coupling to phosphatidylserine (PS) on the inner leaflet of cell membranes specifically, MM@NPs were constructed by macrophage membrane spontaneous encapsulation of cyclodextrin-based nanoparticles modified with the peptide CLIKKPF and loaded with the hydrophobic compound resveratrol. MM@NPs could be specifically phagocytized by the activated endothelium with the overexpressed VCAM-1 for enhancing target delivery into the pathological lesion. Additionally, for the ApoE -/- mice, MM@NPs provide comprehensive treatment efficiency in reducing oxidant stress, alleviating the inherent inflammation, and decreasing cholesterol deposition, subsequently resulting in the atherosclerotic plaque regression. Therefore, MM@NPs could be one possible candidate for improving lipid metabolism and inflammation in atherosclerosis.

Targeted nanoparticles have been extensively explored for their ability to deliver their payload to a selective cell population while reducing off-target side effects. The design of actively targeted nanoparticles requires the grafting of a ligand that specifically binds to a highly expressed receptor on the surface of the targeted cell population. Optimizing the interactions between the targeting ligand and the receptor can maximize the cellular uptake of the nanoparticles and subsequently improve their activity. Here, we evaluated how the density and presentation of the targeting ligands dictate the cellular uptake of nanoparticles. To do so, we used a DNA-scaffolded PLGA nanoparticle system to achieve efficient and tunable ligand conjugation. A prostate-specific membrane antigen (PSMA) expressing a prostate cancer cell line was used as a model. The density and presentation of PSMA targeting ligand ACUPA were precisely tuned on the DNA-scaffolded nanoparticle surface, and their impact on cellular uptake was evaluated. It was found that matching the ligand density with the cell receptor density achieved the maximum cellular uptake and specificity. Furthermore, DNA hybridization-mediated targeting chain rigidity of the DNA-scaffolded nanoparticle offered ∼3 times higher cellular uptake compared to the ACUPA-terminated PLGA nanoparticle. Our findings also indicated a ∼ 3.7-fold reduction in the cellular uptake for the DNA hybridization of the non-targeting chain. We showed that nanoparticle uptake is energy-dependent and follows a clathrin-mediated pathway. Finally, we validated the preferential tumor targeting of the nanoparticles in a bilateral tumor xenograft model. Our results provide a rational guideline for designing actively targeted nanoparticles and highlight the application of DNA-scaffolded nanoparticles as an efficient active targeting platform.

A Pickering emulsion was synergistically stabilised with zein nanoparticles (ZNPs) and starch nanocrystals (SNCs) to prepare it for menthol loading. After response surface optimisation of the emulsion preparation conditions, a Pickering emulsion prepared with a ZNPs:SNCs ratio of 1:1, a particle concentration of 2 wt% and a water:oil ratio of 1:1 provided the highest menthol encapsulation rate of the emulsions tested (83%) with good storage stability within 30 days. We examined the bilayer interface structure of the emulsion by optical microscopy, scanning electron microscopy, and confocal laser scanning microscopy. The results of simulated digestion experiments showed that the release rate of free fatty acid was 75.06 ± 1.23%, which ensured bioavailability. At the same time, the emulsions facilitated the slow release of menthol. Bacteriostatic studies revealed that the Pickering emulsion had a protective effect on menthol, with the most significant inhibitory effects on Escherichia coli and Staphylococcus aureus under the same conditions. Overall, this study proposes a novel approach for the application and development of l-menthol by combining it with Pickering emulsion., Competing Interests: 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 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Atherosclerosis (AS), a pathological cause of cardiovascular disease, results from endothelial injury, local progressive inflammation, and excessive lipid accumulation. AS plaques rich in foam cells are prone to rupture and form thrombus, which can cause life-threatening complications. Therefore, the assessment of atherosclerotic plaque vulnerability and early intervention are crucial in reducing the mortality rates associated with cardiovascular disease. In this work, A fluorescent probe FC-TPA was synthesized, which switches the fluorescence state between protonated and non-protonated, reducing background fluorescence and enhancing imaging signal-to-noise ratio. On this basis, FC-TPA is loaded into cyclodextrin (CD) modified with phosphatidylserine targeting peptide (PTP) and coated with hyaluronic acid (HA) to construct the intelligent responsive diagnostic nanoplatform (HA@PCFT). HA@PCFT effectively targets atherosclerotic plaques, utilizing dual targeting mechanisms. HA binds strongly to CD44, while PTP binds to phosphatidylserine, enabling nanoparticle aggregation at the lesion site. ROS acts as a smart release switch for probes. Both in vitro and in vivo evaluations confirm impressive lipid-specific fluorescence imaging capabilities of HA@PCFT nanoparticles (NPs). The detection of lipid load in atherosclerotic plaque by fluorescence imaging will aid in assessing the vulnerability of atherosclerotic plaque. STATEMENT OF SIGNIFICANCE: Currently, numerous fluorescent probes have been developed for lipid imaging. However, some challenges including inadequate water solubility, nonspecific distribution patterns, and fluorescence background interference, have greatly limited their further applications in vivo. To overcome these limitations, a fluorescent molecule has been designed and synthesized, thoroughly investigating its photophysical properties through both theoretical and experimental approaches. Interestingly, this fluorescent molecule exhibits the reversible fluorescence switching capabilities, mediated by hydrogen bonds, which effectively mitigate background fluorescence interference. Additionally, the fluorescent molecules has been successfully loaded into nanocarriers functionalized with the active targeting abilities, which has significantly improved the solubility of the fluorescent molecules and reduced their nonspecific distribution in vivo for an efficient target imaging in atherosclerosis. This study provides a valuable reference for evaluating the performance of such fluorescent dyes, and offers a promising perspective on the design of the target delivery systems for atherosclerosis., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19 F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H 6 ) to form H 6 -PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H 6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19 F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis., (© 2024. The Author(s).)

Although our understanding of lung cancer has significantly improved in the past decade, it is still a disease with a high incidence and mortality rate. The key reason is that the efficacy of the therapeutic drugs is limited, mainly due to insufficient doses of drugs delivered to the lungs. To achieve precise lung cancer diagnosis and treatment, nano-particles (NPs) pulmonary delivery techniques have attracted much attention and facilitate the exploration of the potential of those in inhalable NPs targeting tumor lesions. Since the therapeutic research focusing on pulmonary delivery NPs has rapidly developed and evolved substantially, this review will mainly discuss the current developments of pulmonary delivery NPs for precision lung cancer diagnosis and therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging., (© 2023 Wiley Periodicals LLC.)

Most existing vaccines, delivered by intramuscular injection (IM), are typically associated with stringent storage requirements under cold-chain distribution and professional administration by medical personnel and often result in the induction of weak mucosal immunity. In this context, we reported a microneedle (MN) patch to deliver chitosan oligosaccharide (COS)-encapsulated DNA vaccines (DNA@COS) encoding spike and nucleocapsid proteins of SARS-CoV-2 as a vaccination technology. Compared with IM immunization, intradermal administration via the MN-mediated DNA vaccine effectively induces a comparable level of neutralizing antibody against SARS-CoV-2 variants. Surprisingly, we found that MN-mediated intradermal immunization elicited superior systemic and mucosal T cell immunity with enhanced magnitude, polyfunctionality, and persistence. Importantly, the DNA@COS nanoparticle vaccine loaded in an MN patch can be stored at room temperature for at least 1 month without a significant decrease of its immunogenicity. Mechanically, our strategy enhanced dendritic cell maturation and antiviral immunity by activating the cGAS-STING-mediated IFN signaling pathway. In conclusion, this work provides valuable insights for the rapid development of an easy-to-administer and thermostable technology for mucosal vaccines.

Herbs containing aristolochic acids (AAs) have already been proven to be highly carcinogenic and nephrotoxic. In this study, a novel surface-enhanced Raman scattering (SERS) identification method was developed. Ag-APS nanoparticles with a particle size of 3.53 ± 0.92 nm were produced by combining silver nitrate and 3-aminopropylsilatrane. The reaction between the carboxylic acid group of aristolochic acid I (AAI) and amine group of Ag-APS NPs was used to form amide bonds, and thus, concentrate AAI, rendering it easy to detect via SERS and amplified to obtain the best SERS enhancement effect. Detection limit was calculated to be approximately 40 nM. Using the SERS method, AAI was successfully detected in the samples of four Chinese herbal medicines containing AAI. Therefore, this method has a high potential to be applied in the future development of AAI analysis and rapid qualitative and quantitative analysis of AAI in dietary supplements and edible herbs., 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.)

In this study, soy protein isolate (SPI) was modified by a pulsed electric field (PEF) combined with pH shifting treatment (10 kV/cm, pH 11) to prepare SPI nanoparticles (PSPI11) for efficient loading of lutein. The results showed that when the mass ratio of SPI to lutein was 25:1, the encapsulation efficiency of lutein in PSPI11 increased from 54% to 77%, and the loading capacity increased by 41% compared to the original SPI. The formed SPI-lutein composite nanoparticles (PSPI11-LUTNPs) had smaller, more homogeneous sizes and larger negative charges than SPI7-LUTNPs. The combined treatment favored the unfolding of the SPI structure and could expose its interior hydrophobic groups to bind with lutein. Nanocomplexation with SPIs significantly improved the solubility and stability of lutein, with PSPI11 showing the greatest improvement. As a result, PEF combined with pH shifting pretreatment is an effective method for developing SPI nanoparticles loaded and protected with lutein., 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 Ltd. All rights reserved.)

Background: The introduction of magnetic resonance (MR)-guided radiation treatment planning has opened a new space for theranostic nanoparticles to reduce acute toxicity while improving local control. In this work, second-generation AGuIX ® nanoparticles (AGuIX-Bi) are synthesized and validated. AGuIX-Bi are shown to maintain MR positive contrast while further amplifying the radiation dose by the replacement of some Gd 3+ cations with higher Z Bi 3+ . These next-generation nanoparticles are based on the AGuIX ® platform, which is currently being evaluated in multiple Phase II clinical trials in combination with radiotherapy. Methods: In this clinically scalable methodology, AGuIX ® is used as an initial chelation platform to exchange Gd 3+ for Bi 3+ . AGuIX-Bi nanoparticles are synthesized with three ratios of Gd/Bi, each maintaining MR contrast while further amplifying radiation dose relative to Bi 3+ . Safety, efficacy, and theranostic potential of the nanoparticles were evaluated in vitro and in vivo in a human non-small cell lung cancer model. Results: We demonstrated that increasing Bi 3+ in the nanoparticles is associated with more DNA damage and improves in vivo efficacy with a statistically significant delay in tumor growth and 33% complete regression for the largest Bi/Gd ratio tested. The addition of Bi 3+ by our synthetic method leads to nanoparticles that present slightly altered pharmacokinetics and lengthening of the period of high tumor accumulation with no observed evidence of toxicity. Conclusions: We confirmed the safety and enhanced efficacy of AGuIX-Bi with radiation therapy at the selected ratio of 30Gd/70Bi. These results provide crucial evidence towards patient translation., Competing Interests: Competing Interests: François Lux and Olivier Tillement have to disclose the patent WO2011/135101. François Lux, Olivier Tillement, and Ross Berbeco have to disclose the patent US62431607. Paul Rocchi, Léna Carmès Tristan Doussineau, and Sandrine Dufort are employees of NH TherAguix which develops AGuIX® nanoparticles. François Lux, Olivier Tillement, Tristan Doussineau, and Sandrine Dufort possess shares in the company, NH TherAguix., (© The author(s).)

Cerium oxide (CeO 2 ) nanoparticles are one of the most important engineered nanomaterials with demonstrated applications in industry. Although numerous studies have reported the plant uptake of CeO 2 , its fate and transformation pathways and mechanisms in plant-related conditions are still not well understood. This study investigated the stability of CeO 2 in the presence of organic ligands (maleic and citric acid) and light irradiation. For the first time, we found that organic ligands and visible light had a synergistic effect on the reductive dissolution of CeO 2 with up to 30% Ce releases after 3 days, which is the highest release reported so far under environmental conditions. Moreover, the photoinduced dissolution of CeO 2 in the presence of citrate was much higher than that in maleate, which are adsorbed on the surface of CeO 2 through inner-sphere and outer-sphere complexation, respectively. A novel ligand-dependent photodissolution mechanism was proposed and highlighted: upon electron-hole separation under light irradiation, the inner-sphere complexed citrate is more capable of consuming the hole, prolonging the life of electrons for the reduction of Ce(IV) to Ce(III). Finally, reoxidation of Ce(III) by oxygen was observed and discussed. This comprehensive work advances our knowledge of the fate and transformation of CeO 2 in plant surroundings.

Gene therapy for autosomal dominant retinitis pigmentosa (adRP) is challenged by the dominant inheritance of the mutant genes, which would seemingly require a combination of mutant suppression and wild-type replacement of the appropriate gene. We explore the possibility that delivery of a nanoparticle (NP)-mediated full-length mouse genomic rhodopsin (gRho) or human genomic rhodopsin (gRHO) locus can overcome the dominant negative effects of the mutant rhodopsin in the clinically relevant P23H +/- -knock-in heterozygous mouse model. Our results demonstrate that mice in both gRho and gRHO NP-treated groups exhibit significant structural and functional recovery of the rod photoreceptors, which lasted for 3 months post-injection, indicating a promising reduction in photoreceptor degeneration. We performed miRNA transcriptome analysis using next generation sequencing and detected differentially expressed miRNAs as a first step towards identifying miRNAs that could potentially be used as rhodopsin gene expression enhancers or suppressors for sustained photoreceptor rescue. Our results indicate that delivering an intact genomic locus as a transgene has a greater chance of success compared to the use of the cDNA for treatment of this model of adRP, emphasizing the importance of gene augmentation using a gDNA that includes regulatory elements., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Compared with traditional medical methods, gene therapy and photodynamic therapy are the new fields of cancer treatment, and they more accurately and effectively obtain preferable therapeutic effects. In this study, a chemotherapy drug-free nanotherapeutic system based on ZIF-90 encapsulated with Ce6-G3139 and Ce6-DNAzyme for gene and photodynamic therapies was constructed. Once entering the cancer cell, the therapy system will decompose and release Zn 2+ , Ce6-G3139, and Ce6-DNAzyme in the acidic environment. On the one hand, G3139 binds to the antiapoptotic gene BCL-2 in tumor cells and downregulates related proteins to inhibit tumor proliferation. On the other hand, Zn 2+ produced by the decomposition of ZIF-90 can be used as a cofactor to activate the cleavage activity of DNAzyme to initiate gene therapy. Proliferation and metastasis of tumors were further inhibited by DNAzyme, targeting and cutting the gene of human early growth factor-1 (EGR-1). In addition, the photosensitizer Ce6 carried by the nucleic acid will produce cytotoxic ROS to kill cancer cells after irradiation. The results of this study demonstrated that the designed nanoplatform, which synergistically combines gene and photodynamic therapies, has shown great potential for cancer treatment.

Foliar application of nanoparticles (NPs) as a means for ameliorating abiotic stress is increasingly employed in crop production. In this study, the potential of CeO 2 -NPs as stress suppressants for cadmium (Cd)-stressed okra (Abelmoschus esculentus) plants was investigated, using two cycles of foliar application of CeO 2 -NPs at 200, 400, and 600 mg/l. Compared to untreated stressed plants, Cd-stressed plants treated with CeO 2 -NPs presented higher pigments (chlorophyll a and carotenoids). In contrast, foliar applications did not alter Cd root uptake and leaf bioaccumulation. Foliar CeO 2 -NPs application modulated stress enzymes (APX, SOD, and GPx) in both roots and leaves of Cd-stressed plants, and led to decreases in Cd toxicity in plant's tissues. In addition, foliar application of CeO 2 -NPs in Cd-stressed okra plants decreased fruit Cd contents, and improved fruit mineral elements and bioactive compounds. The infrared spectroscopic analysis of fruit tissues showed that foliar-applied CeO 2 -NPs treatments did not induce chemical changes but induced conformational changes in fruit macromolecules. Additionally, CeO 2 -NPs applications did not alter the eating quality indicator (Mg/K ratio) of okra fruits. Conclusively, the present study demonstrated that foliar application of CeO 2 -NPs has the potential to ameliorate Cd toxicity in tissues and improve fruits of okra plants., 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 © 2022 Elsevier B.V. All rights reserved.)

Green iron tea nanoparticles (GT-Fe NPs) were used as persulfate(PS) activators to oxidize rhodamine B (RhB) in this study. Optimized oxidative degradation condition was 0.033 mM Fe, 5 mM PS at pH 3.0 and 298 K with an initial RhB content of 50 mg/L. After 120 min of RhB degradation utilizing GT-Fe NPs activated PS, 99% of RhB reduction was achieved, while 98% RhB reduction with PS activated by citric acid-Fe 2+ (CA-Fe) with the same amount of Fe 2+ . This RhB reduction was due to the delayed release of Fe(II) in the GT-Fe NPs. The addition of GT-Fe NPs enhanced the synthesis of OH· and SO 4 - · while inhibiting the formation of O 2 - ·. A possible RhB degradation pathway was the chromophore destruction and ring-opening processes using GT-Fe NPs/PS, which produced a range of low molecular weight carboxylic acids (oxalic acid, lactic acid, acetic acid, and formic acid). GT-Fe NPs seem to be a promising persulfate activator in comparison to common activators such as CA-Fe.

In recent years, laser-mediated photodynamic therapy and photothermal therapy have attracted widespread attention due to their minimally invasive, easy to operate characteristics and high specificity. However, the traditional photodynamic or photothermal therapy exist several shortcomings such as the hypoxic microenvironment, intracellular heat shock proteins or complex operation. In this study, covalent organic framework (COF) was used as the drug carrier to equip with the photosensitizer indocyanine green (ICG) and the hypoxia-activating prodrug AQ4N. The hyaluronic acid (HA) was modified on the surface of COF to obtain the HA-COF@ICG/AQ4N drug delivery system. HA-modified COF delivery systems can target tumor cells through recognize CD44 which is overexpressed in the surface of tumor cells membrane. Under the irradiation of single NIR laser, ICG that can excite the nanoplatform simultaneously produces a combined effect of photodynamic and photothermal. At the same time, photodynamic therapy through depleting intracellular oxygen exacerbates the hypoxic state of the tumor microenvironment, which in turn enhances AQ4N reduced to chemotherapeutic drug AQ4, producing a synergistic cascade antitumor effect. The results of our study by tumor cell and tumor spheroids indicated that the hypoxia-activated multi-functional nanoplatform could effectively inhibit the growth and metastasis of triple-negative breast cancer., 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 © 2022 Elsevier B.V. All rights reserved.)

The aggregation-redispersion behavior of nanomaterials determines their transport, transformation, and toxicity, which could be largely influenced by the ubiquitous natural organic matter (NOM). Nonetheless, the interaction mechanisms of two-dimensional (2D) MoS 2 and NOM and the subsequent influences on the redispersion behavior are not well understood. Herein, we investigated the redispersion of single-layer MoS 2 (SL-MoS 2 ) nanosheets as influenced by Suwannee River NOM (SRNOM). It was found that SRNOM played a decisive role on the redispersion of MoS 2 2D nanosheets that varied distinctly from the 3D nanoparticles. Compared to the poor redispersion of MoS 2 aggregates in the absence or post-addition of SRNOM to the aggregates, co-occurrence of SRNOM in the dispersion could largely enhance the redispersion and mobility of MoS 2 by intercalating into the nanosheets. Upon adsorption to SL-MoS 2 , SRNOM enhanced the hydration force and weakened the van der Waals forces between nanosheets, leading to the redispersion of the aggregates. The SRNOM fractions with higher molecular mass imparted better dispersity due to the preferable sorption of the large molecules onto SL-MoS 2 surfaces. This comprehensive study advances current understanding on the transport and fate of nanomaterials in the water system and provides fresh insights into the interaction mechanisms between NOM and 2D nanomaterials.

Curcumin, a polyphenol derived from turmeric, has multiple biological functions, such as anti-inflammatory, antioxidant, antibacterial and, above all, antitumor activity. Colorectal cancer is a common malignancy of the gastrointestinal tract with an extremely high mortality rate. However, the low bioavailability and poor targeting properties of curcumin generally limit its clinical application. In the present study, we designed a fusion protein GE11-HGFI as a nanodrug delivery system. The protein was connected by flexible linkers, inheriting the self-assembly properties of hydrophobin HGFI and the targeting ability of GE11. The data show that the encapsulation of curcumin by fusion protein GE11-HGFI can form uniform and stable nanoparticles with a size of only 80 nm. In addition, the nanocarrier had high encapsulation efficiency for curcumin and made it to release sustainably. Notably, the drug-loaded nanosystem selectively targeted colorectal cancer cells with high epidermal growth factor receptor expression, resulting in high aggregated concentrations of curcumin at tumor sites, thus showing a significant anticancer effect. These results suggest that the nanocarrier fusion protein has the potential to be a novel strategy for enhancing molecular bioactivity and drug targeting in cancer therapy.

Oxidative stress and mitochondrial damage are the main mechanisms of ischemia-reperfusion injury in ischemic stroke. Herein, cerium oxide nanoparticles with powerful free radical scavenging ability were used as carriers to load dl-3-n-butylphthalide (NBP-CeO 2 NPs) for the combined treatment of ischemic stroke. NBP-CeO 2 NPs could eliminate reactive oxygen species (ROS) in mouse brain microvascular endothelial cells and hippocampal neurons after oxygen-glucose deprivation/reoxygenation (OGD/R), and also save mitochondrial membrane potential, morphology, and function, thus alleviating the in vitro blood brain barrier (BBB) disruption and neuronal apoptosis. In the middle cerebral artery embolization/recanalization (MCAO/R) mouse model, the NBP-CeO 2 NPs also possessed superior ROS scavenging ability, protected mitochondria, and preserved BBB integrity, thereby reducing cerebral infarction and cerebral edema and inhibiting neuroinflammation and neuronal apoptosis. The long-term neurobehavioral tests indicated that the NBP-CeO 2 NPs significantly improved sensorimotor function and spatial learning ability by promoting angiogenesis after ischemic stroke. Therefore, the NBP-CeO 2 NPs provided a novel therapeutic approach for ischemic stroke by combining antioxidant and neurovascular repair abilities, highlighting its wide application in ischemia-reperfusion injury., 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 © 2022 Elsevier Ltd. All rights reserved.)

Melanin is a natural pigment that is widely distributed in many parts of the human body, such as the skin and retinal pigment epithelium (RPE) in eyes. In contrast to skin melanin, which is being constantly synthesized by the epidermal melanocytes, melanin in the RPE does not regenerate. Melanin is known to function as a potential radical scavenger and photoprotective agent. However, the protective effects of melanin against oxidative stress decline with increasing age. This phenomenon has been correlated with the pathogenesis of age-related macular degeneration (AMD). To increase the potential antioxidant and photoprotective characteristics of melanin, we designed a therapeutic strategy for replenishment of melanin using PEGylated synthetic melanin-like nanoparticles (MNPs) in the RPE for the treatment of AMD. We performed experiments using AMD-like cellular and mouse models and demonstrated that MNPs are biocompatible and selectively target reactive oxygen species (ROS) with powerful antioxidant properties. MNPs can traffic and accumulate in the RPE and are exclusively located in cytosol, but not the nucleus and mitochondria of the cells, for at least 3 months after a single-dose intravitreal injection. Our findings demonstrate that MNPs are able to substitute for natural melanin in the RPE and suggest the potential efficacy of MNPs as a natural radical scavenger against oxidative stress in ROS-related diseases, such as AMD.

The present study was to evaluate the potential effectiveness of low-molecular-weight chitosan-coated baicalin methoxy poly(ethylene glycol)-poly(d,l-lactic- co -glycolic acid) (mPEG-PLGA) nanoparticles (BA LCH NPs) for the treatment of cataract. mPEG-PLGA NPs were optimized by the Box-Behnken design and the central composite design based on the encapsulation efficiency and drug loading. Then, the BA LCH NPs were characterized based on morphology, particle size, and zeta potentials. The analytical data of differential scanning calorimetry, X-ray diffraction, and transmission electron microscopy depicted the drug excipient compatibility. In vitro, we evaluated cell viability, cellular uptake, potential ocular irritation, transcorneal permeability, and the precorneal retention of BA LCH NPs. In vivo, the chronic selenium cataract model was selected to assess the therapeutic effect of BA LCH NPs. The size of BA LCH NPs was within the range from 148 to 219 nm and the zeta potential was 19-25 mV. Cellular uptake results showed that the fluorescence intensity of the preparations in each group increased with time, and the fluorescence intensity of the LCH NP group was significantly higher than that of the solution group. The optimized BA LCH NPs improved precorneal residence time without causing eye irritation and also showed a sustained release of BA through the cornea for effective management of cataract. Also, fluorescence tracking on the rabbit cornea showed increased corneal retention of the LCH NPs. In addition, the results of therapeutic efficacy demonstrated that BA LCH NPs can significantly reduce the content of malondialdehyde and enhanced the activities of catalase, superoxide dismutase, and glutathione peroxidase, which was comparable to positive control and better than the BA solution group. Thus, it can be inferred that the BA LCH NPs are a promising drug delivery system for enhancing the ophthalmic administration of BA to the posterior segment of the eye and improving cataract symptoms.

A novel near-infrared (NIR) light-triggered smart nanoplatform has been developed for cancer targeting and imaging-guided combined photothermal-chemo treatment. Notably, Ag 2 S has a dual function of photothermal therapy and fluorescence imaging, which greatly simplifies the structure of the system. It can emit fluorescence at 820 nm under an excitation wavelength of 560 nm. The phase-change molecule of 1-tetradecanol (TD) is introduced as a temperature-sensitive gatekeeper to provide the nanocarrier with controlled release capability of doxorubicin (DOX). The nanocarrier (HAg 2 S@mSiO 2 -TD/DOX) shows a high drug loading capacity of 26.3% and exhibits an apparent NIR-responsive DOX release property. Under NIR irradiation, the photothermal effect of HAg 2 S nanocores facilitated the release of DOX through the melting of TD. The cytotoxicity test shows that the nanocarriers have good biocompatibility. As the same time, the synergistic combination leads to a better cancer inhibition effect than individual therapy alone in vitro. Cell uptake tests indicate that the carriers have excellent fluorescence imaging ability and high cellular uptake for HepG2 cells. This work provides a new strategy for the fabrication of smart nanocarriers with simple structures for fluorescence-mediated combination cancer therapy. Fabrication of a smart drug delivery system based on hollow Ag 2 S@mSiO 2 nanoparticles for fluorescence-guided synergistic photothermal chemotherapy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Effective targeting of nanomedicine is still an intricacy since unsatisfactory clinical trial feedback demonstrated their inadequate concentration at the desired area. However, the regulatory effect of ligand-modification patterns on the targeting effect has not been surveyed yet. Based on the superior spatial addressability of DNA frame structures, herein DNA tetrahedrons were used as templates for site-specific modification of targeting ligands. In this work, nanovectors with homogeneous ligand-modification patterns, including various valence of ligands and the precisely controlled distance between ligands at the nanoscale, were established for the first time. In vitro and in vivo targeting performance studies found that merely relying on the augment of the ligand quantity exhibited a confined promotion effect on the targeting efficiency. Notably, the space distance between ligands displayed a more important role in reforming the targeting effect, and the largest ligand distance (approximately 156.55 Å) pattern exhibited an optimal targeting effect and prominently cytostatic activity toward tumor cells. Generally, the survey of ligand-modification patterns on nanovectors provided a valid guidance to direct the optimization of nanomedicine.

Survival after severe traumatic brain injury (TBI) depends on minimizing or avoiding secondary insults to the brain. Overproduction of reactive oxygen species (ROS) and Ca 2+ influx at the damaged site are the key factors that cause secondary injury upon TBI. Herein, a TBI-targeted lipid covered radical scavenger nanoparticle is developed to deliver nimodipine (Np) (CL-PPS/Np), in order to inhibit Ca 2+ influx in neurons by Np and to scavenge ROS in the brain trauma microenvironment by poly(propylene sulfide) 60 (PPS 60 ) and thus prevent TBI-associated secondary injury. In post-TBI models, CL-PPS/Np effectively accumulates into the wound cavity and prolongs the time of systemic circulation of Np. CL-PPS/Np can markedly protect the integrity of blood-brain barrier, prevent brain edema, reduce cell death and inflammatory responses, and promote functional recovery after TBI. These findings may provide a new therapy for TBI to prevent the spread of the secondary injury., (© 2022 Wiley-VCH GmbH.)

Superior catalytic performance for selective 1,3-butadiene (1,3-BD) hydrogenation can usually be achieved with supported bimetallic catalysts. In this work, Pt-Co nanoparticles and Pt nanoparticles supported on metal-organic framework MIL-100(Fe) catalysts (MIL=Materials of Institut Lavoisier, PtCo/MIL-100(Fe) and Pt/MIL-100(Fe)) were synthesized via a simple impregnation reduction method, and their catalytic performance was investigated for the hydrogenation of 1,3-BD. Pt1Co1/MIL-100(Fe) presented better catalytic performance than Pt/MIL-100(Fe), with significantly enhanced total butene selectivity. Moreover, the secondary hydrogenation of butenes was effectively inhibited after doping with Co. The Pt1Co1/MIL-100(Fe) catalyst displayed good stability in the 1,3-BD hydrogenation reaction. No significant catalyst deactivation was observed during 9 h of hydrogenation, but its catalytic activity gradually reduces for the next 17 h. Carbon deposition on Pt1Co1/MIL-100(Fe) is the reason for its deactivation in 1,3-BD hydrogenation reaction. The spent Pt1Co1/MIL-100(Fe) catalyst could be regenerated at 200 °C, and regenerated catalysts displayed the similar 1,3-BD conversion and butene selectivity with fresh catalysts. Moreover, the rate-determining step of this reaction was hydrogen dissociation. The outstanding activity and total butene selectivity of the Pt1Co1/MIL-100(Fe) catalyst illustrate that Pt-Co bimetallic catalysts are an ideal alternative for replacing mono-noble-metal-based catalysts in selective 1,3-BD hydrogenation reactions., (© 2022 The Authors. Published by Wiley-VCH GmbH.)

Tumor theranostics hold great potential for personalized medicine in the future, and transcatheter arterial embolization (TAE) is an important clinical treatment for unresectable or hypervascular tumors. In order to break the limitation, simplify the procedure of TAE, and achieve ideal combinatorial theranostic capability, here, a kind of triblock-polypeptide-coated perfluoropentane-loaded mesoporous Fe 3 O 4 nanocomposites (PFP- m -Fe 3 O 4 @PGTTCs) were prepared for non-interventional target-embolization, magnetic hyperthermia, and multimodal imaging combination theranostics of solid tumors. The results of systematic animal experiments by H22-tumor-bearing mice and VX2-tumor-bearing rabbits in vivo indicated that PFP- m -Fe 3 O 4 @PGTTC-6.3 has specific tumor accumulation and embolization effects. The tumors' growth has been inhibited and the tumors disappeared 4 weeks and ≤15 days post-injection with embolization and magnetic hyperthermia combination therapy, respectively. The results also showed an excellent effect of magnetic resonance/ultrasound/SPECT multimodal imaging. This pH-responsive non-interventional embolization combinatorial theranostics system provides a novel embolization and multifunctional theranostic candidate for solid tumors.

Background: As cancer is one of the main leading causes of mortality, a series of monotherapies such as chemotherapy, gene therapy and radiotherapy have been developed to overcome this thorny problem. However, a single treatment approach could not achieve satisfactory effect in many experimental explorations., Results: In this study, we report the fabrication of cyclic RGD peptide (cRGD) modified Au 4 -iron oxide nanoparticle (Au 4 -IO NP-cRGD) based on aggregation-induced emission (AIE) as a multifunctional theranostic system. Besides Au 4 cluster-based fluorescence imaging and enhanced radiotherapy, iron oxide (IO) nanocluster could realize magnetic resonance (MR) imaging and Fenton reaction-based chemotherapy. Abundant toxic reactive oxygen species generated from X-ray irradiation and in situ tumor-specific Fenton reaction under acidic microenvironment leads to the apoptotic and necrotic death of cancer cells. In vivo studies demonstrated good biocompatibility of Au 4 -IO NP-cRGD and a high tumor suppression rate of 81.1% in the synergistic therapy group., Conclusions: The successful dual-modal imaging and combined tumor therapy demonstrated AIE as a promising strategy for constructing multifunctional cancer theranostic platform., (© 2021. The Author(s).)

Iodine has shown promise in enhancing radiotherapy. However, conventional iodine compounds show fast clearance and low retention inside cancer cells, limiting their application as a radiosensitizer. Herein, we synthesize poly(maleic anhydride- alt -1-octadecene) coated KI nanoparticles (PMAO-KI NPs) and evaluate their potential for enhancing radiotherapy. Owing to the polymer coating, the KI core of PMAO-KI NPs is not instantly dissolved in aqueous solutions but slowly degraded, allowing for controlled release of iodide (I - ). I - is transported into cells via the sodium iodide symporter (NIS), which is upregulated in breast cancer cells. Our results show that PMAO-KI NPs can enhance radiation-induced production of reactive oxygen species such as hydroxyl radicals. When tested in vitro with MCF-7 cells, PMAO-KI NPs promote radiation-induced DNA double-strand breaks and lipid peroxidation, causing a drop in cancer cell viability and reproductivity. When tested in MCF-7 bearing mice, PMAO-KI NPs show significant radiosensitizing effects, leading to complete tumor eradication in 80% of the treated animals without inducing additional toxicity. Overall, our strategy exploits electrolyte nanoparticles to deliver iodide into cancer cells through NIS, thus promoting radiotherapy against breast cancer.

With the progress made in the widespread application of interventional radiology procedures, there has been an increasing number of patients who suffer from cardiovascular diseases and go through imaging and interventional treatment with iodine contrast medium (ICM) year by year. In turn, there has been an increasing amount of concern over acute kidney injury (AKI) brought about by ICM. As evidenced by numerous studies, the initiation of inflammatory response plays a critical role in the development of ICM-induced AKI. Correspondingly, the strategy of targeting renal inflammatory response and cytokine release could provide an effective solution to mitigating the ICM-induced AKI. Moreover, Ginsenoside Rb1 (GRb1) constitutes one of the major active components of ginseng and features a wide range of vital biological functions. Judging from the research findings, GRb1 could impose antioxidant and anti-inflammatory effects on cardiovascular diseases, in addition to lung, liver and kidney diseases. However, reports on whether GRb1 could impose a protective effect against contrast-induced nephropathy (CIN) are absent. In this study, we have examined the therapeutic effects imposed by GRb1 as well as the potential molecular mechanism by establishing an in vivo and in vitro model of CIN. In addition, we have set up a mouse model of CIN through sequential intravenous injection of indomethacin, N(ω)-nitro-Larginine methyl ester (L-NAME), and iopromide. To further enhance the bioavailability of GRb1, we have encapsulated GRb1 with polyethylene glycol (PEG)/poly lactic-co-glycolic acid (PLGA) nanocarriers to generate GRb1 nanoparticles (NPs) conducting the in vivo experiments. During the in vitro experiments, we have adopted GRb1 to treat NRK-52E cells or cells transfected with the high mobility group box 1 gene (HMGB1) overexpression plasmid. As shown by the in vivo experimental results, GRb1 NPs could evidently improve the renal dysfunction in CIN, diminish the extent of apoptosis of tubular epithelial cells, and reduce the expression of high mobility group box 1 (HMGB1) and cytokines (tumor necrosis factor (TNF-α), interleukin (IL) 6 and IL-1β). In addition, GRb1 NPs are found to be capable of preventing the activation of Toll-like receptor 4 (TLR4)/NF-κB signaling pathway triggered by contrast medium. The in vitro experimental results have exactly confirmed the findings of the in vivo experiments. In the meantime, through the observation of the in vitro assays, overexpression of HMGB1 can partially counteract the beneficial effects imposed by GRb1. Judging from our research data, GRb1 could impose a protective effect against CIN by inhibiting inflammatory response via HMGB1/TLR4/NF-κB pathway, whereas HMGB1 constitutes a critical molecular target of GRb1.

Vitrification can dramatically increase the storage of viable biomaterials in the cryogenic state for years. Unfortunately, vitrified systems ≥3 mL like large tissues and organs, cannot currently be rewarmed sufficiently rapidly or uniformly by convective approaches to avoid ice crystallization or cracking failures. A new volumetric rewarming technology entitled "nanowarming" addresses this problem by using radiofrequency excited iron oxide nanoparticles to rewarm vitrified systems rapidly and uniformly. Here, for the first time, successful recovery of a rat kidney from the vitrified state using nanowarming, is shown. First, kidneys are perfused via the renal artery with a cryoprotective cocktail (CPA) and silica-coated iron oxide nanoparticles (sIONPs). After cooling at -40 °C min -1 in a controlled rate freezer, microcomputed tomography (µCT) imaging is used to verify the distribution of the sIONPs and the vitrified state of the kidneys. By applying a radiofrequency field to excite the distributed sIONPs, the vitrified kidneys are nanowarmed at a mean rate of 63.7 °C min -1 . Experiments and modeling show the avoidance of both ice crystallization and cracking during these processes. Histology and confocal imaging show that nanowarmed kidneys are dramatically better than convective rewarming controls. This work suggests that kidney nanowarming holds tremendous promise for transplantation., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

We herein develop a concentration gradient generator (CGG) on a microfluidic chip for diluting different nanoparticles. Specifically designed compact disk (CD)-shaped microchannels in the CGG module could thoroughly mix the flowing solutions and generate a linear concentration gradient of nanoparticles without aggregation. We combine the CGG with a single-cell trapper array (SCA) on microfluidics to evaluate the concentration-dependent bioeffects of the nanoparticles. The precise control of the spatiotemporal generation of nanoparticle concentration on the CGG module and the single-cell-level monitoring of the cell behaviors on the SCA module by a high-content system in real time, render the CGG-SCA system a highly precise platform, which can exclude the average effect of cell population and reflect the response of individual cells to the gradient concentrations accurately. In addition, the CGG-SCA system provides an automated platform for high-throughput screening of nanomedicines with high precision and low sample consumption., (© 2021 Wiley-VCH GmbH.)

Bacterial/fungal biofilm-mediated persistent endodontic infections (PEIs) are one of the most frequent clinical lesions in the oral cavity, resulting in apical periodontitis and tooth damage caused by loss of minerals. The conventional root canal disinfectants are poorly bio-safe and harmful to teeth and tissues, making them ineffective in treating PEIs. The development of nanomaterials is emerging as a promising strategy to eradicate disease-related bacteria/fungi. Herein, glucose oxidase (GOx)-modified magnetic nanoparticles (MNPs) were synthesized via a facile and versatile route for investigating their effects on removing PEI-related bacterial/fungal biofilms. It is found that GOx was successfully immobilized on the MNPs by detecting the changes in the diameter, chemical functional group, charge, and magnetic response. Further, we demonstrate that GOx-modified MNPs (GMNPs) exhibit highly effective antibacterial activity against Enterococcus faecalis and Candida albicans . Moreover, the antibacterial/fungal activity of GMNPs is greatly dependent on their concentrations. Importantly, when placed in contact with bacterial/fungal biofilms, the dense biofilm matrix is destructed due to the movement of GMNPs induced by the magnetic field, the formation of reactive oxygen species, and nutrient starvation induced by GOx. Also, the in vitro experiment shows that the as-prepared GMNPs have excellent cytocompatibility and blood compatibility. Thus, GMNPs offer a novel strategy to treat bacteria/fungi-associated PEIs for potential clinical applications.

Mounting evidence shows the great promise of nanoparticle drug delivery systems (nano-DDSs) to improve delivery efficiency and reduce off-target adverse effects. By tracking drug delivery and distribution, monitoring nanoparticle degradation and drug release, aiding and optimizing treatment planning, and directing the design of more robust nano-DDSs, image guidance has become a vital component of nanomedicine. Recently, chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has emerged as an attempting imaging method for achieving image-guided drug delivery. One of the unbeatable advantages of CEST MRI is its ability to detect diamagnetic compounds that cannot be detected using conventional MRI methods, making a broad spectrum of bioorganic agents, natural compounds, even nano-carriers directly MRI detectable in a high-spatial-resolution manner. To date, CEST MRI has become a versatile and powerful imaging technology for non-invasive in vivo tracking of nanoparticles and their loaded drugs. In this review, we will provide a concise overview of different forms of recently developed, CEST MRI trackable nano-DDSs, including liposomes, polymeric nanoparticles, self-assembled drug-based nanoparticles, and carbon dots. The potential applications and future perspectives will also be discussed.

Using the DNA origami technique, we constructed a DNA nanodevice functionalized with small interfering RNA (siRNA) within its inner cavity and the chemotherapeutic drug doxorubicin (DOX), intercalated in the DNA duplexes. The incorporation of disulfide bonds allows the triggered mechanical opening and release of siRNA in response to intracellular glutathione (GSH) in tumors to knockdown genes key to cancer progression. Combining RNA interference and chemotherapy, the nanodevice induced potent cytotoxicity and tumor growth inhibition, without observable systematic toxicity. Given its autonomous behavior, exceptional designability, potent antitumor activity and marked biocompatibility, this DNA nanodevice represents a promising strategy for precise drug design for cancer therapy., (© 2020 Wiley-VCH GmbH.)

Quantum dots (QDs) are nanocrystals with bright fluorescence and long-term photostability, attributes particularly beneficial for single-molecule imaging and molecular counting in the life sciences. The size of a QD nanocrystal determines its physicochemical and photophysical properties, both of which dictate the success of imaging applications. Larger nanocrystals typically have better optical properties, with higher brightness, red-shifted emission, reduced blinking, and greater stability. However, larger nanocrystals introduce molecular-labeling biases due to steric hindrance and nonspecific binding. Here, we systematically analyze the impact of nanocrystal size on receptor labeling in live and fixed cells. We designed three (core)shell QDs with red emission (600-700 nm) and crystalline sizes of 3.2, 5.5, and 8.3 nm. After coating with the same multidentate polymer, hydrodynamic sizes were 9.2 nm (QD 9.2 ), 13.3 nm (QD 13.3 ), and 17.4 nm (QD 17.4 ), respectively. The QDs were conjugated to streptavidin and applied as probes for biotinylated neurotransmitter receptors. QD 9.2 exhibited the highest labeling specificity for receptors in the narrow synaptic cleft (∼20-30 nm) in living neurons. However, for dense receptor labeling for molecular counting in live and fixed HeLa cells, QD 13.3 yielded the highest counts. Nonspecific binding rose sharply for hydrodynamic sizes larger than 13.3 nm, with QD 17.4 exhibiting particularly diminished specificity. Our comparisons further highlight needs to continue engineering the smallest QDs to increase single-molecule intensity, suppress blinking frequency, and inhibit nonspecific labeling in fixed and permeabilized cells. These results lay a foundation for designing QD probes with further reduced sizes to achieve unbiased labeling for quantitative and single-molecule imaging.

Introduction: Temozolomide (TMZ) is the first-line chemotherapeutic option to treat glioma; however, its efficacy and clinical application are limited by its drug resistance properties. Polo-like kinase 1 (PLK1)-targeted therapy causes G2/M arrest and increases the sensitivity of glioma to TMZ. Therefore, to limit TMZ resistance in glioma, an angiopep-2 (A2)-modified polymeric micelle (A2PEC) embedded with TMZ and a small interfering RNA (siRNA) targeting PLK1 (siPLK1) was developed (TMZ-A2PEC/siPLK)., Materials and Methods: TMZ was encapsulated by A2-PEG-PEI-PCL (A2PEC) through the hydrophobic interaction, and siPLK1 was complexed with the TMZ-A2PEC through electrostatic interaction. Then, an angiopep-2 (A2) modified polymeric micelle (A2PEC) embedding TMZ and siRNA targeting polo-like kinase 1 (siPLK1) was developed (TMZ-A2PEC/siPLK)., Results: In vitro experiments indicated that TMZ-A2PEC/siPLK effectively enhanced the cellular uptake of TMZ and siPLK1 and resulted in significant cell apoptosis and cytotoxicity of glioma cells. In vivo experiments showed that glioma growth was inhibited, and the survival time of the animals was prolonged remarkably after TMZ-A2PEC/siPLK1 was injected via their tail vein., Discussion: The results demonstrate that the combination of TMZ and siPLK1 in A2PEC could enhance the efficacy of TMZ in treating glioma., Competing Interests: No conflicts of interest were disclosed., (© 2020 Shi et al.)

RNA interference (RNAi) has proven to be a very promising prospect for insect pest control. However, low RNAi efficacy limits further development of this biotechnology for use on lepidopteran insects, including the rice striped stem borer (SSB) (Chilo suppressalis), one of the major destructive rice pests. In this work, the application of various nanoparticles (NPs) by which double-stranded RNA (dsRNA) could be encapsulated was evaluated as an alternative delivery strategy to potentially increase the bioactivity of dsRNA. Three NPs, chitosan, carbon quantum dot (CQD), and lipofectamine2000, complexed with dsRNA (to target the glyceraldehyde-3-phosphate dehydrogenase gene (G3PDH)) were tested to examine their use in controlling SSB. Relative mRNA expressions were quantified using qPCR to evaluate knockdown efficiency of NP-dsRNA treated larvae, and the correlated dsRNA-mediated SSB larval mortality was tested. Thereafter, the content dynamics of hemolymph dsRNA after ingesting different NP-dsRNA were monitored in vivo; the hemolymph dsRNA content was in ratios of 5.67, 9.43, and 1 with chitosan, CQD, and lipofectamine2000 induced samples, respectively. The results demonstrated that all three tested NPs led to efficient feeding delivery by improving both dsRNA stability and cellular uptake equally. Furthermore, there was a strong correlation (r= 0.9854) between the hemolymph dsRNA contents and the average RNAi depletions in the non-gut tissues of SSB. Overall, our results strongly suggest that due to its strong endosomal escaping ability, CQD was the most efficient carrier for inducing systemic RNAi, and thereby causing effective gene silencing and mortality in SSB., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Herein, we evaluate the use of MRI as a tool for assessing iron oxide nanoparticle (IONP) distribution within IONP perfused organs and vascularized composite allografts (VCAs) (i.e., hindlimbs) prepared for cryopreservation., Methods: Magnetic resonance imaging was performed on room-temperature organs and VCAs perfused with IONPs and were assessed at 9.4 T. Quantitative T 1 mapping and T 2 ∗ -weighted images were acquired using sweep imaging with Fourier transformation and gradient-echo sequences, respectively. Verification of IONP localization was performed through histological assessment and microcomputer tomography., Results: Quantitative imaging was achieved for organs and VCAs perfused with up to 642 mM Fe (36 mg Fe /mL), which is above previous demonstrations of upper limit detection in agarose (35.7mM Fe [2 mg Fe /mL]). The stability of IONPs in the perfusate had an effect on the quality of distribution and imaging within organs or VCA. Finally, MRI provided more accurate IONP localization than Prussian blue histological staining in this system, wherein IONPs remain primarily in the vasculature., Conclusion: Using MRI, we were able to assess the distribution of IONPs throughout organs and VCAs varying in complexity. Additional studies are necessary to better understand this system and validate the calibration between T 1 measurements and IONP concentration., (© 2019 International Society for Magnetic Resonance in Medicine.)

Cardiac glycosides (CGs) have been used to treat cancer for hundreds of years. However, the narrow therapeutic window and system toxicity have hindered their wide clinical applications. Herein, the small molecule prodrug strategy and nanotechnology were integrated into one drug delivery system with enhanced therapeutic effect. Using periplocymarin (PPM) as a target agent, we designed a novel redox-responsive prodrug conjugated with linoleic acid (PPM-ss-LA), which was capable of self-assembling independent of exogenous excipients. This prodrug could co-assemble with DSPE 2k to form PEGylated prodrug nanoparticles (PPM-ss-LA/DSPE 2k -NPs) with enhanced colloidal stability and blood circulation. Compared with free PPM, PPM-ss-LA/DSPE 2k -NPs retained high anti-proliferative activity and showed increased cell uptake and therapeutic efficacy. Furthermore, the PPM-ss-LA/DSPE 2k -NPs acquired a greatly enhancement of 50% lethal dose (LD 50 ) in mice and reduced system toxicity compared with the free drug. Overall, the on-demand release of nanoprodrug delivery system could improve the therapeutic window and anticancer efficacy of CGs., 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 © 2019 Elsevier B.V. All rights reserved.)

The use of gene therapy may allow replacement of the defective gene. Minigenes, such as cDNAs, are often used. However, these may not express normal physiological genetic profiles due to lack of crucial endogenous regulatory elements. We constructed DNA nanoparticles (NPs) that contain either the mouse or human full-length rhodopsin genomic locus, including endogenous promoters, all introns, and flanking regulatory sequences of the 15-16 kb genomic rhodopsin DNA inserts. We transduced the NPs into primary retinal cell cultures from the rhodopsin knockout (RKO) mouse in vitro and into the RKO mouse in vivo and compared the effects on different functions to plasmid cDNA NP counterparts that were driven by ubiquitous promoters. Our results demonstrate that genomic DNA vectors resulted in long-term high levels of physiological transgene expression over a period of 5 months. In contrast, the cDNA counterparts exhibited low levels of expression with sensitivity to the endoplasmic reticulum (ER) stress mechanism using the same transgene copy number both in vitro and in vivo. This study demonstrates for the first time the transducing of the rhodopsin genomic locus using compacted DNA NPs., (Published by Elsevier Inc.)

Dark tea-iron nanoparticles (DT-Fe NPs) were prepared using extracts of dark tea leaves as a reducing agent, and further underwent thermal treatment in air. The H 2 S removal performances of thermal-treated DT-Fe NPs for biogas were further evaluated using a custom-designed fixed-bed reactor (reaction temperature of 250°C, H 2 S content of 1%). Significant morphology and chemical composition differences were observed when DT-Fe NPs were treated at different temperatures (300-800 o C). X-ray diffractometer analysis revealed that a phase transition from γ-Fe 2 O 3 to α-Fe 2 O 3 occurred under heat treatment. When the thermal treatment temperature was 300°C, only α-Fe 2 O 3 was detected. Both α-Fe 2 O 3 and γ-Fe 2 O 3 were present in the sample treated at 400°C. When the thermal treatment temperature was 500-800°C, γ-Fe 2 O 3 in the sample was completely converted to α-Fe 2 O 3 . The H 2 S removal capacity is 14.72 mg H 2 S/g for DT-Fe NPs without treatment. However, the value increased significantly to 408.30 mg H 2 S/g after 400°C thermal treatment, which can be explained by the formation of highly active γ-Fe 2 O 3 . The reaction product of thermal-treated DT-Fe NPs at 400°C and H 2 S were further characterized by X-ray diffractometer and X-ray photoelectron spectroscopy. The results showed that it is composed of FeS 2 and FeS, in which 72.6% of the sulphur existed as disulphide and 27.4% as monosulphide.

Bacterial nanocellulose (BNC) has many advantages over plant cellulose, which make it widely used in many fields, especially in the food industry. In this study, three strains including BCA263, BCC529, and P1 were selected for characteristics analysis of BNCs under static and agitated culture conditions. The BNCs produced under static culture condition were in the shape of uniform membrane, while BNCs produced under agitated culture were in form of small agglomerates and fragments. BCA263 and BCC529 strains were more suitable for static culture, while P1 strain was more suitable for agitated culture. BNCs produced under static culture condition exhibited higher crystallinity, stronger tensile strength, denser network structure, higher temperature resistance and good flame retardancy; while BNCs produced under agitated culture condition exhibited larger porous and lower crystallinity. Furthermore, BNCs produced under agitated culture condition were more suitable as a stabilizer of coffee milk beverage., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Dry eye (DE) disease is an uprising health epidemic that directly affects the surface of the eye. We developed a water soluble cerium oxide loaded glycol chitosan nanoparticle as a new type of eye drop, namely GCCNP (glycol chitosan cerium oxide nanoparticles). GCCNP is capable of scavenging cellular reactive oxygen species (ROS) for the treatment of DE disease. The antioxidative effects of GCCNP were assessed in mice primary corneal and conjunctival cells in vitro and in a DE murine model in vivo. GCCNP's effect on the DE models was assessed via histological evaluations, migration assays, cell viability assays, cellular uptake analyses, intracellular ROS scavenging assays, wound healing assays, mitochondrial membrane potential readings, corneal fluorescein staining, tear volume concentrations, tear film break up time analyses, and lastly, analytical/spectroscopic analyses of GCCNP eye drop formulations. Spectroscopic analysis showed that cerium oxide was entrapped into the glycol chitosan (GC). The solubility of cerium in GC (GCCNP) increased to 709.854±24.3μg/ml compared to its original solubility in cerium oxide, which was measured as 0.020±0.002μg/ml. GCCNP had no cytotoxic effect and showed improvements on dry eye disease models by stabilizing the tear film, scavenging ROS, up-regulating SOD, promoting and maintaining corneal and conjunctival cell growth and integrity. We provided convincing evidence that GCCNP is an effective treatment for DE and may represent a potential new class of drug for DE disease., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Cancer immunotherapy can enhance the antitumor effect of drugs through a combinatorial approach in a synergistic manner. However, the effective targeted delivery of various drugs remains a challenge. We generated a peptide assembling tumor-targeted nanodelivery system based on a breast cancer homing and penetrating peptide for the codelivery of a programmed cell death ligand 1 (PD-L1) small interfering RNA (siRNA) (siPD-L1) and an indoleamine 2,3-dioxygenase inhibitor as a dual blockade of an immune checkpoint. The vector is capable of specifically accumulating in the breast cancer tumor site in a way that allows the siRNA to escape from endosomal vesicles after being endocytosed by tumor cells. The drug within these cells then acts to block tryptophan metabolism. The results showed that locally released siPD-L1 and 1-methyl-dl-tryptophan favor the survival and activation of cytotoxic T lymphocytes, resulting in apoptosis of breast cancer cells. Therefore, this study provides a potential approach for treating breast cancer by blocking immunological checkpoints through the assembly of micelles with functional peptides.

The molecular response of animals to nanoplastic particles is still largely unclear. In this study, we employed a modified prolonged exposure system to investigate the molecular response of Caenorhabditis elegans to nanopolystyrene particles. Exposure to nanopolystyrene particles (1 μg/L) significantly decreased expressions of daf-2 encoding an insulin receptor, age-1 encoding a PI3K, and akt-1 encoding an Akt/PKB, and increased expression of daf-16 encoding a FOXO transcriptional factor in insulin signaling pathway. Among these genes, mutation of daf-2, age-1, or akt-1 induced a resistance to toxicity of nanopolystyrene particles, whereas mutation of daf-16 induced a susceptibility to the toxicity of nanopolystyrene particles. RNAi knockdown of daf-16 could further suppress the resistance of daf-2, age-1, or akt-1 mutant to the toxicity of nanopolystyrene particles. The insulin signaling pathway acted in intestinal cells to regulate the toxicity of nanopolystyrene particles. Moreover, sod-3 encoding a manganese superoxide dismutase, mtl-1 encoding a metallothionein, and gpd-2 encoding a glyceraldehyde-3-phosphate dehydrogenase were identified as downstream targeted genes for daf-16 in the regulation of toxicity of nanopolystyrene particles. Therefore, a signaling cascade of DAF-2-AGE-1-AKT-1-DAF-16-SOD-3/MTL-1/GPD-2 was identified in response to nanopolystyrene particles in nematodes. Additionally, this signaling cascade in the insulin signaling pathway may mediate a protective response for nematodes against the adverse effects from nanopolystyrene particles.

Programmable drug delivery systems hold great promise to enhance cancer treatment. Herein, a programmable drug delivery system using a chondroitin sulfate (CS)-based composite nanoparticle was developed for enhancing and sensitizing chemotherapy to drug-resistant cancer. The nanoparticle was composed of a cross-linked CS hydrogel shell and hydrophobic cores containing both free drugs and CS-linked prodrugs. Interestingly, the nanoparticle could mediate tumor-specific CD44 targeting. After specific cellular uptake, the payloads were suddenly released because of the decomposition of the CS shell, and the free drug molecules with synergistic effects induced tumor-specific cytotoxicity rapidly. Subsequently, the inner cores of the nanoparticles sustainedly release their cargos in drug-resistant tumor cells to keep the effective drug concentration against the drug efflux mediated by P-glycoprotein. CS dissociated from the outer shell and sensitized cancer cells to the antitumor drugs through downregulation of Bcl-XL, an antiapoptosis protein. Such a programmable drug delivery system with specific tumor-targeting and sensitized therapy is promising for rational drug delivery and provides more versatility for controlled release in biomedical applications.

This work demonstrated the design and synthesis of multiple dye-doped silica cross-linked micellar nanoparticles (MD-SCMNPs) by encapsulating three organic dyes (fluorescein derivative (FCD), coumarin derivative (HCE) and Rhodamine b (RhB)) in SCMNPs cores for colour-tuneable sensing of cysteine (Cys) in aqueous media and in living cells. In the presence of Cys, HCE exhibited blue emission, and RhB exhibited purple emission, while FCD reacted with Cys and exhibited green fluorescence "turn-on" in the core of MD-SCMNPs. This green-light-emitting sensing product may cause "step by step" fluorescent resonance energy transfer (FRET) from HCE to the sensing product and then to RhB. Based on the FRET process in the core, MD-SCMNPs can quantitatively detect Cys by a colour change with a low limit of detection (LOD) of 0.3 μM in living cells. Furthermore, MD-SCMNPs exhibited ultrasmall size (∼12 nm) and excellent dispersity and biocompatibility, which could potentially be used as a visualized Cys sensor for health monitoring and disease prediction in the human body., (Copyright © 2018. Published by Elsevier Inc.)

The rapid development and application of nanotechnology have led to increasing concern about the environmental implications of released nanomaterials and potential risks to public health and aquatic ecosystems. Information on the joint effect of nanomaterials and co-existing contaminants such as heavy metals is still inadequate. Our work investigated the effect of Al 2 O 3 nanoparticles (NPs; nano-Al 2 O 3 ) on the toxic effect of Pb in the unicellular marine phytoplankton Isochrysis galbana. Results showed that a dose-response effect of nano-Al 2 O 3 was found. Significant enhancement of fluorescence in cell cytoplasm rather than cell membrane occurred in the presence of nano-Al 2 O 3 , indicating that nano-Al 2 O 3 can penetrate cells and affect the fluorescence emitted from the chloropigments inside them. The presence of nano-Al 2 O 3 has no impact on the toxic effect of Pb at an NP concentration of 1 mg/L but increased that at NP concentrations of 10 mg/L and 100 mg/L. A synergistic effect was also found for the toxic effect of Pb in the presence of 10 mg/L nano-Al 2 O 3 . The presence of 100 mg/L nano-Al 2 O 3 significantly increased the bio-uptake of Pb in the range of 0.25 mg/L to 2.0 mg/L Pb, and the maximum accumulated Pb in algae can reach up to 18.22 ng/10 5 cells with 100 mg/L nano-Al 2 O 3 compared with Pb alone at 2.0 mg/L(12.53 ng/10 5 cells). Inside cells, Pb loaded onto nano-Al 2 O 3 can be more toxic than the same amount of free Pb species. The results of toxicity tests and accumulated Pb in algae imply that, in addition to the total Pb cell content, the bioavailability of Pb inside algae should be taken into consideration in evaluating the joint toxicity effect. Our work enhances understanding of the combined toxicity of NPs and co-existing heavy metals and is of practical significance in the natural environment., (Copyright © 2018 Elsevier Inc. All rights reserved.)