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Realizing the immense clinical potential of mRNA-based drugs will require continued development of methods to safely deliver the bioactive agents with high efficiency and without triggering side effects. In this regard, lipid nanoparticles have been successfully utilized to improve mRNA delivery and protect the cargo from extracellular degradation. Encapsulation in lipid nanoparticles was an essential factor in the successful clinical application of mRNA vaccines, which conclusively demonstrated the technology's potential to yield approved medicines. In this review, we begin by describing current advances in mRNA modifications, design of novel lipids and development of lipid nanoparticle components for mRNA-based drugs. Then, we summarize key points pertaining to preclinical and clinical development of mRNA therapeutics. Finally, we cover topics related to targeted delivery systems, including endosomal escape and targeting of immune cells, tumors and organs for use with mRNA vaccines and new treatment modalities for human diseases., (© 2024. The Author(s).)

The cellular uptake of nanoparticles (NPs) by biological cells is an important and fundamental process in drug delivery. Previous studies reveal that the physicochemical properties of nanoparticles as well as those of functionalized ligands can both critically affect the uptake behaviors. However, the effect of the conjugation strategy (i.e., the "bond" between the ligand and the NP) on the cellular uptake is overlooked and remains largely elusive. Here, by taking the broadly employed gold nanoparticle as an example, we comprehensively assessed the relationship between the conjugation strategy and uptake behaviors by introducing three ligands with the same functional terminal but different anchoring sites. As revealed by in vitro cell experiments and multiscale molecular simulations, the uptake efficiency of gold NPs was positively correlated with the strength of the "bond" and more specifically the ligand mobility on the NP surface. Moreover, we validated the results presented above by proposing a thermodynamic theory for the wrapping of NPs with mobile ligands. Further, we also showed that the endocytic pathway of NPs was highly dependent on ligand mobility. Overall, this study uncovered a vital role of conjugation strategy in the cellular uptake and may provide useful guidelines for tailoring the biobehaviors of nanoparticles.

Neutral nanomaterials functionalized with PEG or similar molecules have been popularly employed as nanomedicines. Compared to positive counterparts that are capable of harnessing the well-known proton sponge effect to facilitate their escape from lysosomes, it is yet unclear how neutral substances got their entry into the cytosol. In this study, by taking PEGylated, neutral Au nanospheres as an example, we systematically investigated their time-dependent translocation postuptake. Specifically, we harnessed dissipative particle dynamics simulations to uncover how nanospheres bypass lysosomal entrapment, wherein a mechanism termed as "squeezing-out" mode was discovered. We next conducted a comprehensive investigation on how nanomaterials implicate lysosomes in terms of integrity and functionality. By using single-molecule imaging, specific preservation of PEG-terminated with targeting moieties in lysosomes supports the "squeezing-out" mode as the mechanism underlying the lysosomal escape of nanomaterials. All evidence points out that such a process is benign to lysosomes, wherein the escape of nanomaterials proceeds at the expense of targeting moieties loss. Furthermore, we proved that by fine-tuning of the efficacy of nanomaterials escaping from lysosomes, modulation of distinct pathways and metabolic machinery can be achieved readily, thereby offering us a simple and robust tool to implicate cells.

The fluorinated decorations have recently been widely used in many biomedical applications. However, the potential mechanism of the fluorination effect on the cellular delivery of nanoparticles (NPs) still remains elusive. In this work, we systemically explore the penetration of a perfluoro-octanethiol-coated gold NP (PF-Au NP) and, for comparison, an octanethiol-coated gold NP (OT-Au NP) across lipid bilayers. We also investigated the effect of these two types of NPs on the properties of lipid bilayers. Our findings indicate that the lipid type and the surface tension of the lipid bilayer significantly impact the penetration capabilities of the fluorinated gold NP. By examining the distribution of ligands on the surface of the two types of NPs in water and during the penetration process, we unveil their distinct penetration characteristics. Specifically, the PF-Au NP exhibits amphiphobic behavior (both hydrophobic and lipophobic), while the OT-Au NP exhibits solely hydrophobic characteristics. Finally, we observe that the penetration capabilities can be increased by adjusting the degree of fluorination of the ligands on the NP surface. Overall, this study provides useful physical insights into the unique properties of the fluorinated decorations in NP permeation.

mRNA-based drugs have tremendous potential as clinical treatments, however, a major challenge in realizing this drug class will promise to develop methods for safely delivering the bioactive agents with high efficiency and without activating the immune system. With regard to mRNA vaccines, researchers have modified the mRNA structure to enhance its stability and promote systemic tolerance of antigenic presentation in non-inflammatory contexts. Still, delivery of naked modified mRNAs is inefficient and results in low levels of antigen protein production. As such, lipid nanoparticles have been utilized to improve delivery and protect the mRNA cargo from extracellular degradation. This advance was a major milestone in the development of mRNA vaccines and dispelled skepticism about the potential of this technology to yield clinically approved medicines. Following the resounding success of mRNA vaccines for COVID-19, many other mRNA-based drugs have been proposed for the treatment of a variety of diseases. This review begins with a discussion of mRNA modifications and delivery vehicles, as well as the factors that influence administration routes. Then, we summarize the potential applications of mRNA-based drugs and discuss further key points pertaining to preclinical and clinical development of mRNA drugs targeting a wide range of diseases. Finally, we discuss the latest market trends and future applications of mRNA-based drugs., (© 2023. National Science Council of the Republic of China (Taiwan).)

Alzheimer's disease (AD) is the most common neurodegenerative disease, which is associated with extracellular deposition of amyloid- β proteins (A β ). It has been reported that triptolide (TP), an immunosuppressive and anti-inflammatory agent extracted from a Chinese herb Tripterygium wilfordii , shows potential neuroprotective effects pertinent to AD. However, the clinical use of TP for AD could be hampered due to its high toxicity, instability, poor water solubility, and nonspecific biodistribution after administration. In this paper, we reported a kind of multiple-coated PLGA nanoparticle with the entrapment of TP and surface coated by chitosan hydrochloride, Tween-80, PEG20000, and borneol/mentholum eutectic mixture (MC-PLGA-TP-NP) as a novel nasal brain targeting preparation for the first time. The obtained MC-PLGA-TP-NP was 147.5 ± 20.7 nm with PDI of 0.263 ± 0.075, zeta potential of 14.62 ± 2.47 mV, and the entrapment efficiency and loading efficiency of 93.14% ± 4.75% and 1.17 ± 0.08%, respectively. In comparison of TP, MC-PLGA-TP-NP showed sustained-release profile and better transcellular permeability to Caco-2 cells in vitro. In addition, our data showed that MC-PLGA-TP-NP remarkably reduced the cytotoxicity, attenuated the oxidative stress, and inhibited the increase of the intracellular Ca 2+ influx in differentiated PC12 cells induced by A β 1-42 . Therefore, it can be concluded that MC-PLGA-TP-NP is a promising preparation of TP, which exerts a better neuroprotective activity in the AD cellular model., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2021 Lu Jia et al.)

Natural organic matter (NOM) that forms coronas on the surface of engineered nanoparticles (NPs) affects their stability, bio-uptake, and toxicity. After corona formation, a large amount of unbound NOM remains in the environment and their effects on organismal uptake of NPs remain unknown. Here, the effects of unbound NOM on the uptake of polyacrylate-coated hematite NPs (HemNPs) by the protozoan Tetrahymena thermophila were examined. HemNPs were well-dispersed without any detectable NOM adsorption. Kinetics experiments showed that unbound NOM decreased the uptake of HemNPs with greater inhibition at lower concentrations of the particles in the presence of NOM of higher molecular weight. The unbound NOM suppressed clathrin-mediated endocytosis but not the phagocytosis of HemNPs. Confirmation of these events was obtained using label-free hyperspectral stimulated Raman spectroscopy imaging and dissipative particle dynamics simulation. Overall, the present study demonstrates that unbound NOM can compete with HemNPs for internalization receptors on the surface of T. thermophila and inhibit particle uptake, highlighting the need to consider the direct effects of unbound NOM in bioapplication studies and in safety evaluations of NPs.

It is important to maintain the balance between therapeutic efficiency and cytotoxicity when using nanomaterials for biomedical applications. Here, we propose a new method (i.e., non-covalent coating of protected copolymers onto the nanoparticle surface) to enhance the active targeting of nanoparticles to the cancer cells by combining the dissipative particle dynamics simulation and in vitro experiments. When coating the protected copolymer onto the nanoparticle surface, the uptake efficiency could be greatly altered due to the competition between the copolymer-ligand interaction and the receptor-ligand interaction-the non-covalent coating is more efficient than the covalent coating. Furthermore, the effect of the physicochemical properties of the protected copolymer on the targeting ability of nanoparticles was also investigated. This study offers useful insight into the optimal design of nanocarriers in biomedicine.

Control over the protein corona of nanomaterials allows them to function better. Here, by taking graphene/gold as examples, we comprehensively assessed the association of surface properties with the protein corona. As revealed by in vitro measurements and computations, the interaction between graphene/gold and HSA/IgE was inversely correlated with the hydroxyl group availability, whereas the interaction between that and ApoE was comparatively less relevant. Molecular simulations revealed that the number and the distribution of surface hydroxyl groups could regulate the manner in which nanomaterials interact with proteins. Moreover, we validated that ApoE pre-adsorption before injection enhances the blood circulation of nanomaterials relative to their pristine and IgE-coated counterparts. This benefit can be attributed to the invulnerability of the complementary system provided by ApoE, whose encasement does not increase cytotoxicity. Overall, this study offers a robust yet simple way to create protein corona enriched in dysopsonins to realize better delivery efficacy.

The well control over the cell-nanoparticle interaction can be of great importance and necessity for different biomedical applications. In this work, we propose a new and simple way (i.e., polymeric tether) to tuning the interaction between nanoparticles and cell membranes by dissipative particle dynamics simulations. It is found that the linked nanoparticles (via polymeric tether) can show some cooperation during the cellular uptake and thereby have a higher wrapping degree than the single nanoparticle. The effect of the property of the polymer on the wrapping is also investigated, and it is found that the length, rigidity, and hydrophobicity of the polymer play an important role. More interestingly, the uptake of linked nanoparticles could be adjusted to the firm adhesion via two rigid polymeric tethers. The present study may provide some useful guidelines for novel design of functional nanomaterials in the experiments.

Efficient and accurate detection of cancer cells (from normal cells) is of great importance in cancer diagnosis and prognosis. In this work, we design a new type of polymeric substrate containing nanoparticles for detecting cancers by the dissipative particle dynamics (DPD) simulation. It is found that the cancer cells and the normal cells can be indeed distinguished since the uptake number of nanoparticles from the substrate is different. The competition between the nanoparticle-cell specific interaction and nanoparticle-polymer non-specific interaction is the main factor for different uptake behaviors. Moreover, the dynamics of the nanoparticle diffusion in the polymer layer also plays an important role in the detection. To improve the detection accuracy, we further investigate the effect of the polymer type and density as well as the ligand type on the detection, and find that there may exist an optimal parameter to maximize the difference between cancer cells and normal cells. The present study may provide useful insights into the design of functionalized substrate-based nanodevices in biomedicine.

Background: The aim of this study was to explore the feasibility of delivering tumor antigens and enhancing the antigen cross-presentation of dendritic cells (DCs) by aluminum hydroxide nanoparticle with polyethyleneimine (PEI) modification (LV@HPA/PEI)., Materials and Methods: The LV@HPA nanoparticles were modified by PEI first, then the influence of LV@HPA/PEI on DCs was examined. The distinct expression of ovalbumin (OVA) protein transported into DCs by LV@HPA/PEI was observed by flow cytometry and Western blot. The biocompatibility of LV@HPA/PEI, maturity and antigen cross-presentation of DCs was observed in vitro. Tumor derived autophagosomes (DRibbles) combined with LV@HPA/PEI were loaded into DCs, and DC vaccines were used to immunize mice. The percentage of CD3 + CD8 + IFN-γ + T cells in immunized mice was determined by flow cytometry. Additionally, the functional properties of the LV@HPA/PEI-DRibble-DCs vaccine were examined in vivo in PancO2 tumor-bearing mice., Results: In our study, we described how LV@HPA/PEI can be a functionalized antigen delivery system with notable antigen transport effect and negligible cytotoxicity. It was found that LV@HPA/PEI could be easily internalized into DCs to assist antigen release into the cytoplasm. In addition, DCs matured gradually after loading with LV@HPA/PEI-OVA, which increased significantly the cytokine IL-12 secretion and expression of surface molecules CD80 and CD86. Interestingly, DCs loaded with LV@HPA/PEI-DRibbles could promote the activation of tumor-specific T cells both in murine and in human T cells. In the following in vivo experiments, the vaccine of LV@HPA/PEI-DRibble-DCs significantly inhibited tumor growth and improved the survival rate of the PancO2 tumor-bearing mice., Conclusion: We established a high-performance anti-tumor vaccine of DCs loaded with LV@ HPA/PEI nanoparticles and tumor-associated antigens in autophagosomes (DRibbles), which could serve as a therapeutic strategy in cancer immunotherapy., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

A facile and sensitive method for the quantitative detection of telomerase and in situ imaging of intracellular telomerase is developed by using a graphene oxide (GO)-based fluorescent nanosensor. The nanosensor consists of a fluorescent DNA (P1) adsorbed on the GO surface. Here, GO serves not only as a fluorescence quencher but also as a carrier to successfully transport P1 into cancer cells as a signal reporter. P1 is a dye-labeled single-stranded DNA complementary to the telomeric repeated sequence, and initially the combination of P1 and GO exhibits minimal background fluorescence. When telomerase extends its repeat units of TTAGGG on the 3'-end of the primer-DNA, the fluorescence of P1 is subsequently recovered because the telomeric repeated sequence can hybridize with P1 and liberate it from the GO surface. This method enables the determination of telomerase activity down to 10 cells. For the in situ detection of telomerase, upon endocytosis of the P1/GO combinatorial probe into living cancer cells, the intracellular telomerase extends its primer to produce the telomeric repeated sequence and then turns on the fluorescence of P1, which can be directly monitored by confocal laser scanning microscopy. The feasibility of the assay is further investigated by treating with telomerase-related drugs, and the results demonstrate its potential in antitumor drug screening and cancer therapy evaluation.

A simple and effective strategy was developed to enrich ubiquitinated proteins (UPs) from cancer cell lysate using the α-Al 2 O 3 nanoparticles covalently linked with ubiquitin binding protein (Vx3) (denoted as α-Al 2 O 3 -Vx3) via a chemical linker. The functionalized α-Al 2 O 3 -Vx3 showed long-term stability and high efficiency for the enrichment of UPs from cancer cell lysates. Flow cytometry analysis results indicated dendritic cells (DCs) could more effectively phagocytize the covalently linked α-Al 2 O 3 -Vx3-UPs than the physical mixture of α-Al 2 O 3 and Vx3-UPs (α-Al 2 O 3 /Vx3-UPs). Laser confocal microscopy images revealed that α-Al 2 O 3 -Vx3-UPs localized within the autophagosome of DCs, which then cross-presented α-Al 2 O 3 -Vx3-UPs to CD8 + T cells in an autophagosome-related cross-presentation pathway. Furthermore, α-Al 2 O 3 -Vx3-UPs enhanced more potent antitumor immune response and antitumor efficacy than α-Al 2 O 3 /cell lysate or α-Al 2 O 3 /Vx3-UPs. This work highlights the potential of using the Vx3 covalently linked α-Al 2 O 3 as a simple and effective platform to enrich UPs from cancer cells for the development of highly efficient therapeutic cancer vaccines.

Dual ligand targeting to different types of over-expressed receptors on cell surfaces is a promising strategy in nanomedicine. Here, by using dissipative particle dynamics simulations, the effect of the surface distribution and physicochemical properties of dual ligands on the cellular uptake of nanoparticles is systematically studied. It is found that the spontaneous rearrangement of dual ligands (from random to patterned distribution) on the nanoparticle surface can enhance the cellular uptake of nanoparticles. While the short length of ligands may restrict the ligand rearrangement, nanoparticles coated with short dual ligands cannot be fully wrapped by cell membranes unless the dual ligands are initially separated on the nanoparticle surface. Besides, when there exists a length mismatch or non-specific interaction between the dual ligands, dual-ligand targeting cannot enhance the uptake efficiency, either. Further, we also provide the design guidelines for surface decoration, and find that the Janus nanoparticle can make the most of dual-ligand targeting. These results can help understand how to better use dual ligands to achieve efficient cellular uptake, which may provide significant insights into the optimal design of future nanomaterials in drug delivery.

Understanding the role of surface decoration of nanoparticles in protein adsorption and cellular uptake is of great importance in biomedicine. Here, by using dissipative particle dynamics simulations, we take two typical coating polymers (i.e., hydrophilic and zwitterionic polymers) as an example, and systematically investigate their effect on cellular delivery of hydrophobic and charged nanoparticles (in the presence of serum protein). Our results show that though two types of polymers are charge-neutral and can both reduce the protein adsorption, there exist some differences between their ability of protein resistance, especially in the case of positively charged nanoparticles. Besides, it is found that the coating polymers may also greatly decrease the cellular uptake efficiency of nanoparticles. Nevertheless, and importantly, since the zwitterionic polymers may become positively charged under low pH environments, the nanoparticle can attach onto cell membrane more firmly than that coated with hydrophilic polymers, which can further enhance the active targeting of nanoparticles. Finally, we also provide the design maps for surface decoration to achieve efficient cellular delivery. These results can help better understand how to keep the balance between protein resistance and cell targeting, which may give some useful guidelines on optimal design of future nanomaterials in drug delivery.

With the rapid development of nanotechnology, nanoparticles have been widely used in many applications such as phototherapy, cell imaging, and drug/gene delivery. A better understanding of how nanoparticles interact with bio-system (especially cells) is of great importance for their potential biomedical applications. In this review, the current status and perspective of theoretical and computational investigations is presented on the nanoparticle-biomembrane interactions in cellular delivery. In particular, the determining parameters (including the properties of nanoparticles, cell membranes and environments) that govern the cellular uptake of nanoparticles (direct penetration and endocytosis) are discussed. Further, some special attention is paid to their interactions beyond the translocation of nanoparticles across membranes (e.g., nanoparticles escaping from endosome and entering into nucleus). Finally, a summary is given, and the challenging problems of this field in the future are identified., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Understanding the role of serum protein in the process of nanoparticle delivery is of great importance in biomedicine. Here, by using dissipative particle dynamics simulations, we systematically investigate the interactions between the nanoparticle-protein corona complex and cell membranes of different types. It is found that the human serum albumin (HSA) will just adsorb onto charged (especially for positively charged) and hydrophobic nanoparticle surface. More importantly, we also provide specific insights into the effect of HSA adsorption on the in vivo transportation of nanoparticle (i.e., immune response and targeted cellular uptake). Our results show that the protein corona can change the interaction modes of hydrophobic nanoparticles and enhance the interaction of charged nanoparticles with macrophage cell membranes, while it may also cause the failure of insertion of hydrophobic nanoparticles and the loss of targeting specificity of charged nanoparticles with cancer cell membranes. These results can help better understand the biological significance of protein corona and may give some useful suggestions on better design of future nanoparticles in drug delivery., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The major challenge in cancer therapy is to efficiently translocate drug molecules into cancer tumors without doing any damage to healthy tissues. Since there exist pH gradients between tumor and normal tissues, pH-sensitive materials may have great potential to overcome such challenge. Here, we report one new type of pH-responsive drug delivery system where pH-sensitive polymers are introduced to control the cellular uptake of nanoparticles under different pH environments through dissipative particle dynamics simulations. Interestingly, the behavior of cellular uptake of nanoparticles here exhibits "smart" pH-responsive properties: for lower and higher pH, the nanoparticles can be taken up by cell membranes, while for pH in middle range, the endocytosis is blocked. Further, it is found that receptor-ligand interactions as well as surface charge property of nanoparticles and membranes can also have important impacts on the endocytosis. The present study may give some significant insights into future stimulus-responsive medical materials design.

A fundamental understanding of the receptor-mediated endocytosis is of great importance in biomedicine. In this paper, we systematically investigate the effect of the properties of coating ligands on the cellular uptake of nanoparticles by using dissipative particle dynamics, and find that the strength of the receptor-ligand interaction, the ligand density and length as well as its rigidity can strongly affect the final equilibrium in the receptor-mediated endocytosis. Interestingly, it is found that the particle decorated with longer ligands is more likely to attach to the membrane, while it is harder to be totally engulfed. Increasing the ligand density and rigidity which enhances the uniform distribution of ligands on the particle may lead to the total engulfment. Further, we also show that the particle can be totally engulfed if one can reasonably design the hydrophobic/lipophobic properties of ligands. The present study shows that not only the chemical but also the physical parameters of ligands can govern the nanoparticle-cell interaction, which may give some significant insights into future nanoparticle design in drug delivery., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Nanoparticle penetration into cells is an important process in drug/gene delivery. Here, we successfully design one type of novel nanoparticles with ligands decorating its surface by dynamic bonds and find that the nanoparticle can spontaneously penetrate through membranes by using dissipative particle dynamics simulations. Moreover, the physical parameters of both ligands (for example, ligand type and density) and nanoparticles (such as size and shape) have significant effects on penetration efficiency and translocation time. Especially for nanoparticles with anisotropic shapes or asymmetric surface decoration, the penetration efficiency may reach about 80%. We also provide insights into the interaction between nanoparticles and asymmetric membranes and find that the membrane asymmetry can even increase the penetration efficiency to above 90%. The present study suggests a potential way to translocate novel nanoparticles through membranes, which may provide new ideas for future experimental nanoparticle design and drug delivery.

Therapeutic cancer vaccination is an attractive strategy because it induces T cells of the immune system to recognize and kill tumour cells in cancer patients. However, it remains difficult to generate large numbers of T cells that can recognize the antigens on cancer cells using conventional vaccine carrier systems. Here we show that α-Al(2)O(3) nanoparticles can act as an antigen carrier to reduce the amount of antigen required to activate T cells in vitro and in vivo. We found that α-Al(2)O(3) nanoparticles delivered antigens to autophagosomes in dendritic cells, which then presented the antigens to T cells through autophagy. Immunization of mice with α-Al(2)O(3) nanoparticles that are conjugated to either a model tumour antigen or autophagosomes derived from tumour cells resulted in tumour regression. These results suggest that α-Al(2)O(3) nanoparticles may be a promising adjuvant in the development of therapeutic cancer vaccines.

Aim: To investigate the influence of particle size and methoxypolyethyleneglycol (MePEG) molecular weight on the in vitro macrophage uptake and in vivo long circulating of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha)-loaded stealth nanoparticles in rats., Methods: Three sizes (approximately 80, 70 and 240 nm) of poly (methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles loading rHuTNF-alpha were prepared at different MePEG molecular weights (Mr 2,000, 5,000, 10,000) using the double emulsion method. The in vitro macrophage uptake and in vivo long circulating properties in rats were examined and compared., Results: The uptake by macrophages decreased and the half-life of rHuTNF-alpha in rat increased with the increase of MePEG molecular weight or the decrease of particle size. The linear-ships between particle size and MePEG molecular weight and the in vitro macrophage uptake and in vivo long circulating properties were fairly good. Having the highest MePEG surface density (1.32 nm(-2)) , the shortest average distance between neighboring MePEG chain (0.87 nm) and the thicker fixed aqueous layer thickness (FALT, 5.16 nm), PEG5,000-PHDCA nanoparticles (80.0 nm) earned the strongest potency of decreasing uptake by macrophages and prolonging the half-life of rHuTNF-alpha in rat., Conclusion: Within the experimental limits, particle size and MePEG molecular weight had dramatic influence on in vitro macrophage uptake and in vivo long circulating properties of rHuTNF-alpha-loaded stealth nanoparticles.

Abstract: It has been reported that a Pt‐based concave‐convex structure offers good electrocatalytic activity toward the oxygen reduction reaction (ORR). Herein, we synthesize ternary PtPdCu multicubes with a hierarchical trepanning concave‐convex structure by a facile solvothermal co‐reduction method. By tailoring the elementary composition, the optimal Pt45Pd30Cu25/C catalyst results in a 2.35‐fold increase in ORR mass activity compared to commercial Pt/C and an excellent long‐term stability. Investigation reveals that the performance enhancement mechanism is mainly caused by the Pd and Cu jointly modified electronic structure of Pt, which facilitates the charge transfer rate as well as the increased number of active sites and improved mass transport by the unique porous multicube concave‐convex structure. Both experiment and theoretical calculations reveal that the three‐elements alloy catalyst and the unique structures play a critical role in high catalytic performance, thus offering guidance to design high‐performance electrocatalysts not only toward the ORR for practical applications in low‐temperature fuel cells, but also for other energy conversion systems rendering a universal significance. [ABSTRACT FROM AUTHOR]

Vaterite calcium carbonate hierarchical structures with a flowerlike appearance have been successfully synthesized by means of a nanoparticle-mediated self-organization process in an ethanol/water mixed solution system under mild conditions without using any organic additives. A mechanism for the formation of vaterite crystal aggregates with flowerlike structures made of decussate 'cigars' is presented. There are two points that play important roles in the regular organization of the terminal products: one is the concentration of carbonate, and the other is the volume ratio of ethanol/double-distilled water. In view of the results, a nanoparticle-mediated self-organization process is helpful in controlling the aggregation-driven formation of complex higher-order-structured materials and will provide new insights into biomineralization mechanisms. This study could provide an additional tool for designing advanced materials and could be used for the synthesis of more complex crystalline three-dimensional structures. [ABSTRACT FROM AUTHOR]

The major challenge in cancer therapy is to efficiently translocate drug molecules into cancer tumors without doing any damage to healthy tissues. Since there exist pH gradients between tumor and normal tissues, pH-sensitive materials may have great potential to overcome such challenge. Here, we report one new type of pH-responsive drug delivery system where pH-sensitive polymers are introduced to control the cellular uptake of nanoparticles under different pH environments through dissipative particle dynamics simulations. Interestingly, the behavior of cellular uptake of nanoparticles here exhibits "smart" pH-responsive properties: for lower and higher pH, the nanoparticles can be taken up by cell membranes, while for pH in middle range, the endocytosis is blocked. Further, it is found that receptor-ligand interactions as well as surface charge property of nanoparticles and membranes can also have important impacts on the endocytosis. The present study may give some significant insights into future stimulus-responsive medical materials design [ABSTRACT FROM AUTHOR]

Design and fabrication of hybrid plasmonic structures by laser means are investigated to extend flexible tuning of optical properties of metallic micro/nano-structures for high-sensitivity detection and enhancement of solar cell antireflection performance for high energy-conversion efficiency. It is shown that the identical micro/nano-structures in well-defined arrays fabricated by laser interference lithography can be used as a versatile platform to enhance fluorescence intensity of the molecules. Meanwhile, postprocessing of such structures via thermal annealing can result in ordered clusters of nanodots 50 nm in average size, which enhances Raman scattering intensity. A dramatic reduction in silicon surface reflectance is achieved via pulsed fiber laser texturing. The suppression of reflectance can be further improved by decorating the laser-textured Si surface with metallic nanoparticles by thermal annealing of metallic thin films deposited on the Si surfaces. This hybrid plasmonic structure scheme can achieve broadband (300–1000 nm) antireflection with a surface reflection as low as 5.5%. The improved broadband antireflection of the surfaces could have applications in solar energy, renewable energy, and electrooptical devices. [ABSTRACT FROM PUBLISHER]

To search for more efficient and inexpensive electrocatalysts is one of the main research directions for the electrocatalytic application of direct liquid fuel cells. Nanohybrid Pt/NiO/MWCNTs are synthesized by impregnation and polyol methods. Two different series denoted as Pt/[NiO/MWCNTs (1:4)] and NiO/[Pt/MWCNTs (1:4)] are prepared. The sizes of the nanoparticles are 3-7 nm and 10 nm for Pt and NiO, respectively. By observing the morphology images, NiO will aggregate more on Pt modified MWCNTs than those without Pt adding. The catalytic properties of these hybrid catalysts are characterized by methanol electro-oxidation. The addition of 20 wt% NiO, before or after Pt synthesis, can better enhance the catalysis ability of Pt and help Pt catalyst convert CO in lower temperature. This study indicates the 10 wt% Pt/[NiO/MWCNTs (1:4)] catalyst has the best performance in electrocatalytic activity for methanol. The NiO is a cheaper material than other commonly used oxides; the novel hybrid catalysts are a promised candidate for the electrocatalytic application in DMFCs. [ABSTRACT FROM AUTHOR]

Colloidal Ag nanoparticles were formed by X-ray irradiation in the presence of a polymer. This new synthesis method is simple, rapid and leads to a high production yield. Compared to the citrate-reduced Ag colloidal, polymer-protected Ag nanoparticles are smaller in size and more stable—and therefore suitable for biomedical application—as verified by TEM observation, XAFS measurement and optical characterization. Ag nanoparticles so produced were also visualized in solution and in real time by a visible light microscope based on dark field light scattering. The color-derived size and distribution of Ag nanoparticles correlates well with the hydrodynamic size data. [ABSTRACT FROM AUTHOR]

The remarkable enhancement of electron transfer on screen-printed carbon electrodes (SPCEs) with modification by iron nanoparticles (Fenano), coupled with Fe(CN)6 4−/3− redox species, was characterized with an increase of electroactive area ( A ea) at electrode surface together with a decrease of heterogeneous electron transfer rate constant ( k°) in the system. Hence, Fenano-Fe(CN)6 3− SPCEs with deposition of glucose oxidase (GOD) demonstrated a higher sensitivity to various glucose concentrations than Fe(CN)6 3−/GOD-deposited SPCEs. In addition, an inhibited diffusion current from cyclic voltammograms was also observed with an increase in redox concentration and complicated the estimation of A ea. Further analysis by the electrochemical impedance method, it was shown that this effect might be resulted from the electrode surface blocking by the products of activated complex decomposition. [ABSTRACT FROM AUTHOR]

This article presents the development of an innovative approach using the vacuum submerged arc machining with aid of enhanced ultrasonic vibration to manufacture nanoparticles. The Arc Spray Nanoparticle Synthesis System (ASNSS) previously designed by the NTUT’s Nano Laboratory has been successfully developed to generate nanoparticles. In this proposed process, a titanium bar, as the electrode, is melted and vaporized in distilled water, used as an insulating liquid. Meanwhile, the ultrasonic vibration is applied to the electrode to remove the vaporized metal powders rapidly from the melting zone. The vaporized metal particles are then rapidly quenched by the designed cooling system, thus nanocrystalline particles nucleated and formed. This study discusses the the influence of the ultrasonic amplitude and various process variables such as pulse duration, peak current, and dielectric liquid temperature on TiO2nanoparticles suspension. [ABSTRACT FROM AUTHOR]

This article presents the development of an innovative technology to manufacture TiO2 nanoparticles. Manufacturing nanoparticles is considered as a crucial step towards product and process innovation. In our proposed process, a titanium rod, as the electrode, is melted and vaporised in deionised water, which is used as an insulating liquid. The vaporised metal particles are then rapidly quenched by the designed cooling system, and thus nanocrystalline powders are nucleated and formed. By implementing the system, we have successfully developed the processing equipment of the arc spray nanoparticle synthesis system (ASNSS). The experimental results indicate that uniformly distributed and well-controlled TiO2 nanoparticle size can be manufactured by ASNSS. [ABSTRACT FROM AUTHOR]

Efficient delivery of nanoparticles into specific cell interiors is of great importance in biomedicine. Recently, the pH-responsive micelle has emerged as one potential nanocarrier to realize such purpose since there exist obvious pH differences between normal tissues and tumors. Herein, by using dissipative particle dynamics simulation, we investigate the interaction of the pH-sensitive triblock copolymer micelles composed of ligand (L), hydrophobic block (C) and polyelectrolyte block (P) with cell membrane. It is found that the structure rearrangement of the micelle can facilitate its penetration into the lower leaflet of the bilayer. However, when the ligand-receptor specific interaction is weak, the micelles may just fuse with the upper leaflet of the bilayer. Moreover, the ionization degree of polyelectrolyte block and the length of hydrophobic block also play a vital role in the penetration efficiency. Further, when the sequence of the L, P, C beads in the copolymers is changed, the translocation pathways of the micelles may change from direct penetration to Janus engulfment. The present study reveals the relationship between the molecular structure of the copolymer and the uptake of the pH-sensitive micelles, which may give some significant insights into the experimental design of responsive micellar nanocarriers for highly efficient cellular delivery. [ABSTRACT FROM AUTHOR]