Subjects Science Chemistry Nonfiction. Named after the two-faced roman god, Janus particles have gained much attention due to their potential in a variety of applications, including drug delivery. This is the first book devoted to Janus particles and covers their methods of synthesis, how these particles self-assemble, and their possible uses.
By following the line of synthesis, self-assembly and applications, the book not only covers the fundamental and applied aspects, but it goes beyond a simple summary and offers a logistic way of selecting the proper synthetic route for Janus particles for certain applications. Written by pioneering experts in the field, the book introduces the Janus concept to those new to the topic and highlights the most recent research progress on the topic for those active in the field and catalyze new ideas.
Science Chemistry Nonfiction. More about Zhenzhong Yang. New here? Learn how to read digital books for free.
[Full text] Janus particles: recent advances in the biomedical applications | IJN
Required Cookies These cookies allow you to explore OverDrive services and use our core features. These non-lamellar lipid NPs have received increasing attraction as nanocarriers for drugs, 4 , 12 , 43 , 44 genes, 45 , 46 and imaging contrast agents 7 due to their unique self-assembled nanostructures, which control the drug release rate, encapsulation capacity of both hydrophobic and hydrophilic compounds, and cellular interactions. However, before the potential of these lipid Janus NPs can be unlocked, a formulation process to produce them consistently and in large quantity is needed.
Beside polymeric and organic-based Janus NPs, anisotropic particles containing two inorganic compartments have also received increasing level of attention. Among inorganic Janus NPs found in literature, the majority of them were developed based on the inherent therapeutic effects of heavy metals and heavy metal oxides. The Janus functionality not only preserves the original properties of each NP components but also provides new properties not present in single-component NPs due to the interfacial interaction originating from electron transfer across the nanoscale contact.
For a more detailed summary on the synthesis of inorganic Janus NPs, the readers are referred to a review article by Schick et al. An in vitro study then demonstrated the enhanced anticancer effect of the dual-loaded Janus NPs against HeLa cells. Furthermore, real-time release of 6MP was observed through the change of surface-enhanced Raman scattering of 6MP. Such dual-release and real-time monitoring of multiple drugs were believed to be possible due to the special structure of the Janus NPs, which allow for the combination of drastically different chemical or physical properties and directionalities within a single particle.
Intelligent Janus nanoparticles for intracellular real-time monitoring of dual drug release. This improved anti-tumor efficacy was attributed to the FA active targeting and the simultaneous release of both ICG and silver ions without mutual interference, a feature that was made possible due to the Janus structure. C Photographs of the excised tumors from mice from each group. This synthesis route was proven to be versatile as the same group replaced Ag with Fe 3 O 4 and created magnetic Janus NPs.
In these cases, the presence of the Fe 3 O 4 compartment contributes to tumor targeting mediated by the EPR effect and magnetic field-enhanced endocytosis. Ultimately, both in vitro and in vivo studies of subcutaneous and orthotropic liver tumor models in mice showed that the magnetic Janus NPs suppressed of the liver tumor growth and significantly reduced systemic toxicity.
It should be noted that prior to these studies core—shell type magnetic MS NPs had been reported. The Janus structure of the NP allows two drugs to be simultaneously loaded and their release independently controlled. Azobenzene, a UV-vis light-sensitive molecule, was used to control the release of DOX from this compartment. Finally, 1-tetradecanol phase change material was used as another switch to control the release of PTX. This design resulted in Janus NPs with dual-controlled release of two drugs with different solubility.
An in vitro study was performed by incubating the nanocomposites with HeLa cells to validate the feasibility of this drug delivery system. The results showed that the Janus NPs with and without drugs did not significantly affect cell viability in the absence of a stimuli source ie, heat or NIR light. This indicated the negligible amount of drugs released. Figure 6 A Synthetic procedure for dual compartment Janus mesoporous silica nanocomposites. B Schematic illustration for dual-control drug release systems by using the dual-compartment mesoporous Janus nanocomposites.
Anisotropic growth-induced synthesis of dual-compartment Janus mesoporous silica nanoparticles for bimodal triggered drugs delivery. J Am Chem Soc. In an attempt to encapsulate and rapidly deliver drug, a self-propelled Janus nanomotor system was developed by Xuan et al. In this case, platinum acted as an engine that decomposes hydrogen peroxide to generate oxygen as a driving force to propel the NP. As a proof-of-concept, the NPs were loaded with anticancer drug DOX and coated with phosphatidylcholine PC bilayers containing folic acid to enhance the adhesion of the NPs on the surface of cancer cells.
One key issue with this system was the toxicity of hydrogen peroxide to mammalian cellular functions, thereby limiting the concentration of hydrogen peroxide in cell culture medium and consequently the maximum speed of the nanomotors. A recent study from the same group showed that by replacing platinum catalysts enzymes, more powerful and efficient polymer-based motors can be achieved, requiring lower peroxide concentrations at physiological temperature. Inorganic-based Janus NPs have also been explored for non-viral delivery of genes and vaccines. Notable examples are the works involving gold-nickel Janus nanorods from the Leong group.
The nanorods were modified further by using molecular linkages to attach DNA molecules to the nickel segments and transferrin, a cell-targeting protein, to the gold segments. The results showed that the nanorods were uptaken by the cells and led to much higher transfection efficiency of both GFP and luciferase-encoded plasmids in human embryonic kidney cells HEK , especially in the case of transferrin-conjugated nanorods Figure 7B — D. Preliminary in vivo efficacy studies were performed in the skin and muscle tissues of mice showing vastly different transgene expressions over time. For example, luciferase activity in the skin by nanorods transfection peaked early times higher than background and decreased quickly to 80 times above background after 4 days.
In contrast, intramuscular delivery of the nanorods resulted in only 17 times higher luciferase expression than the background after 1 day, but it was more prolonged, with a luciferase level 85 times above background at day Although promising, further investigation on these nanorods is needed because nickel has toxicity concerns. B Rhodamine red nm identifies the subcellular location of the nanorods whilst GFP expression green nm provides confirmation of transfection. Orthogonal sections confirm that the nanorods are within the cell.
Janus Particle Synthesis and Assembly
C HEK cell stained with Lysotracker Green shows the location of the nanorods Rhodamine - red in relation to acidic organelles in both orthogonal sections. Multifunctional nanorods for gene delivery. Nat Mater. Since both polymeric and inorganic materials have their own advantages for therapeutic applications, the combination of polymer and inorganic compartments into a Janus composite NP is logical.
In contrast, when the solution was heated in the presence of the hydrophilic ligand alone, mainly AuNSs without a polymer shell were generated. Interestingly, the authors showed that the degree of coverage could be tuned by adjusting the solvent ratio and the ligand ratio. The polymer-free areas on the particle surfaces were further modified with single-stranded DNA. Due to the fine selective regional modification, the inter-particle binding potential was directional and selective, resulting in the potential for increasingly complex self-assembly.
Figure 8 Directional and programmable encapsulated NPs. Top row: colloidal metallic NPs with different sizes, shapes, and compositions, which can be converted into regioselective NPs rseNPs through polymer blocking and DNA modification. Second row: controllable polymer blocking will break the homogeneous surface chemistry of NPs, creating specific binding sites on it.
Third row: DNA modification on polymer-free surface region provides a specific binding force on the binding site. Bottom row: images of the corresponding rseNPs. Scale bars, 20 nm. Regioselective surface encoding of nanoparticles for programmable self-assembly. The multi-functionalities of the NPs were attributed to their Janus structure, which allowed the NPs more room to perform different functions for cancer therapy compared with the traditional core—shell NPs. The targeting of LA was proven to be effective by both in vitro cell uptake and in vivo biodistribution experiments in HepG2 cells and H tumor-bearing mice, respectively.
The synthesis concept reported in this work was modified to produce different types of Janus NPs. The dual drug-loaded Janus NPs demonstrated synergistic hydrophobic and hydrophilic chemotherapy and photothermal therapy in vitro and in vivo. D Representative photograph of excised H tumors from mice at 11 days post treatment. Tailored synthesis of octopus-type janus nanoparticles for synergistic actively-targeted and chemo-photothermal therapy. Angew Chem Int Ed. The synthesis of these Janus NPs appeared to be fairly complicated with 4 main steps: 1 preparation of the core particle, 2 the hydrophilic part, 3 the hydrophobic part, and 4 conjugating both sides on a NP Figure Finally, the hydrophobic side DOX-PCL-yne was conjugated to the core particles via alkyne-azide cycloaddition click reaction.
Cell uptake study showed that after 5 hrs of incubation with folate receptor expressed C6 glioma cells, the Janus NPs were internalized at a much higher level compared to the FA-free Janus NPs, indicating the effectiveness of the FA targeting functionality. Int J Pharm. Medical imaging plays important roles in disease detection, prognosis, and treatment planning. For many of these techniques, a contrast agent is needed to improve the image quality.
Additionally, due to each imaging method has its own benefits and limitations, there have been a strong interest in combining complement imaging modalities into a single platform. By incorporating small molecules, these NPs can find applications in nearly all imaging modalities. Due to their anisotropic structure, Janus NPs have the advantage of comprising two different faces, which not only enable two complementary imaging modalities but also offer two functional surfaces for the attachment of different kinds of molecules, making them especially attractive as multifunctional probes.
Figure 11 shows representative TEM images corresponding to NPs formed at different nanodumbbell seed concentrations and constant amount of gold precursor. Compared with core—shell NPs, the Janus morphology resulted highly beneficial in several aspects, offering high availability of the iron oxide surface, which consequently gives rise to high r 2 relaxivity values and Prussian blue staining ability. As the NP size decreases, the iron oxide part light grey can be distinguished from the gold domain dark grey or black.
Janus plasmonic—magnetic gold—iron oxide nanoparticles as contrast agents for multimodal imaging. Dumbbell-shaped inorganic Janus NPs have also attracted much attention as multifunctional probes for diagnostic and therapeutic applications. For example, Xu et al reported dumbbell gold-iron oxide NPs, which were coated with a layer of oleate and oleylamine. The dumbbell NPs were demonstrated to be capable of imaging the exact same tissue area through both MRI and an optical source without the fast signal loss observed in the common fluorescent labeling.
It was suggested that they could be used to achieve high sensitivity in diagnostic imaging applications. Au—Fe 3 O 4 dumbbell nanoparticles as dual-functional probes. This was attributed to the synergistic effect seen when both Au and Fe 3 O 4 were present within a single particle.
More importantly, the NPs demonstrated dual contrast capability in vivo when intravenously injected into hepatoma-bearing mice. The scale bar in the TEM image indicates 20 nm. In a study by Schick et al, the Au-MnO Janus NPs were prepared by a seed-mediated nucleation and growth method, which allowed precise control over domain sizes, surface functionalization, and dye labeling Figure 14A and B.
Time-resolved fluorescence spectroscopy in combination with confocal laser scanning microscopy CLSM revealed the Janus NPs to be highly two-photon active due to the presence of the Au domain. However, the study did not explicitly show the magnetic property and MRI contrast capability of the synthesized Janus NPs. Multifunctional two-photon active silica-coated Au MnO Janus particles for selective dual functionalization and imaging. So far, most Janus NPs for theranostics have been either inorganic—inorganic or polymer—inorganic composite. Although dose-dependent toxicity profiles were observed in all tested cell lines, the DOX-loaded Ag-MS Janus NPs displayed significantly lower damage to normal cells compared to cancer cells.
The selective toxicity of these NPs was attributed to the pH-sensitively drug release behavior, as well as the higher endocytosis capacity of the NPs in tumor cells. Another strategy to achieve theranostics is by combining the property of magnetic NPs as a contrast agent for MRI with photothermal or photodynamic therapy. Additionally, a chemotherapeutic agent maybe incorporated to further improve the efficacy of the system. The authors demonstrated a synergistic anticancer therapy in vitro and in vivo in HepG2 cells and H hepatocarcinoma tumor bearing mice, respectively Figure 15B — F. Selective growth synthesis of ternary Janus nanoparticles for imaging-guided synergistic chemo- and photothermal therapy in the second NIRwindow.
Several polymeric-inorganic composite Janus NPs for theranostics have been reported by the Li and Wang groups. The combined treatment resulted in an impressive Chem Sci. The Janus structure of the NPs allowed them to express multiple functions simultaneously and interpedently.
In vitro, the Janus NPs showed a significant photothermal effect with a Additionally, the heating of the NPs and tumor locally was monitored by thermal IR imaging. Monodisperse Au—Fe 2 C Janus nanoparticles: an attractive multifunctional material for triple-modal imaging-guided tumor photothermal therapy. ACS Nano. In addition to applications in therapeutics and in vivo imaging, Janus particles have also been developed as biosensors.
The existing literature can be classified into two categories. One category involves utilizing the compartmentalization within Janus particles into different domains, which serve as independent biological recognition and signal transduction modalities. Compared to the second category of moving biosensors, the first type of Janus particles can be regarded as static. Isotropic NPs have been studied widely as biosensors.
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The surfaces of these NPs are often functionalized with large biomolecules such as proteins or DNAs to provide binding sites for analytes. However, the presence of these biomolecules on particle surfaces can sometimes interfere with the sensing functions and reduce their efficacy. Janus particles with two separated faces and properties may provide elegant alternatives to decouple binding and sensing functions for these biosensors.
Han et al developed retroreflective Janus microparticles RJPs as a novel optical immunosensing probe for use in a nonspectroscopic retroreflection-based immunoassay.
Janus particles: synthesis, self-assembly, physical properties, and applications.
The gold outer layer was used to functionalize reacting antibodies on to particle surfaces. Once the antibodies bind to a substrate, the RJPs were able to provide bright retroreflection signals which were easily detected using polychromatic white light-emitting diode LED irradiation Figure 18B and C. The same group demonstrated the tunability of these Janus particles by conjugating streptavidin instead of antibodies to the gold surface of the RJPs Figure 18D.
When the mercury ions are absent, the assistant DNA probe does not hybridize with the stem-loop probe due to their thymine-thymine T-T mismatch. The surface-immobilized stem-loop DNA probe, therefore, remains a closed hairpin structure. Streptavidin-modified RJPs are used as the optical signaling label to recognize the exposed biotin. Figure 18 A Schematic diagram for the strategy of the proposed retroreflective cardiac troponin I cTnI sandwich immunoassay using RJP as an optical immunosensing probe.
B Retroreflective road signs at night time. C Schematic illustrations and figures of retroreflective immunosensing surface before left and after right the white LED illumination.
Retroreflective Janus microparticle as a nonspectroscopic optical immunosensing probe. Biosens Bioelectron. These Janus particles with one hydrophilic and one hydrophobic side were developed as an electrochemical sensor for the determination of ractopamine RAC. For this sensor, the hydrophobic part of the Janus particle was immobilized onto the surface of electrode. The electrochemical sensor fabrication process is shown in Figure When RAC was present, the interaction of RAC with the aptamer resulted in the hinder of the electron transition from the electrode surface.
The detection limit of this electrochemical sensor was 3. The proposed electrochemical sensor can be successfully applied to the determination of RAC in spiked human urine samples with good stability and reproducibility. Figure 19 Schematic illustration of the electrochemical sensor fabrication process for the detection of ractopamine RAC. The detection relies on the change in peak current of the sensor in the absence A and the presence B of RAC. Sens Actuat B Chem.
Biji and Patnaik studied Janus gold nanoclusters for sensing dopamine, an important neurotransmitter in the mammalian central nervous system.
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The subphase L-tryptophan acted as the reductant and capping agent at the lower hemisphere. The Janus scheme for the in situ formed clusters is illustrated in Figure 20A. The sensitivity of dopamine detection depended on the 2D phase state, assembly, and organization of the Janus monolayer cluster. These also controlled the electronic communication between the clusters as a function of the intercluster distance, size, and orientation, ultimately influencing the electrocatalytic oxidation of the bio-analyte with improved sensitivity and detection limit.
The study suggested that the non-covalent nature of the ligands on the core metal clusters facilitated the overall electro-catalytic oxidation of dopamine, as shown in Figure 20B. It was found that directed Brownian motion of the spherically charged clusters dictated by the 2D interfacial surface pressure was the driving force for the characteristic Janus cluster assembly into 1D Janus chains with varied dopamine detection efficiency.
Figure 20 A Janus structure of the gold nanoclusters formed at the air—water interface. The blue arrows represent the redox reaction of dopamine at the gold nanocluster surface. The white arrow shows the electronic communication between the Janus cluster mediators to the glassy carbon electrode. Reprinted with permission from Biji P, Patnaik A. Interfacial Janus gold nanoclusters as excellent phase- and orientation-specific dopamine sensors.
Miniaturizing biosensors have attracted much attention from the research community due to the potential to improve their sensitivity and portability, while reducing cost and material requirements. Shan Jiang received his B. He subsequently became a postdoctoral fellow at Massachusetts Institute of Technology, working on drug delivery and biomedication.
With more than refereed publications to his name, he has long-standing research interests in tribology as well as in the dynamics of polymers, complex fluids, colloids, and phospholipid membranes. Jump to main content. Jump to site search. Journals Books Databases. Search Advanced. Current Journals.
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