ISCOMs/MPLA-Adjuvanted SDAD Protein Nanoparticles Induce Improved Mucosal Immune Responses and Cross-Protection in Mice

The epidemics caused by the influenza virus are a serious threat to public health and the economy. Adding appropriate adjuvants to improve immunogenicity and finding effective mucosal vaccines to combat respiratory infection at the portal of virus entry are important strategies to boost protection. In this study, a novel type of core/shell protein nanoparticle consisting of influenza nucleoprotein (NP) as the core and NA1-M2e or NA2-M2e fusion proteins as the coating antigens by SDAD hetero-bifunctional crosslinking is exploited. Immune-stimulating complexes (ISCOMs)/monophosphoryl lipid A (MPLA) adjuvants further boost the NP/NA-M2e SDAD protein nanoparticle-induced immune responses when administered intramuscularly. The ISCOMs/MPLA-adjuvanted protein nanoparticles are delivered through the intranasal route to validate the application as mucosal vaccines. ISCOMs/MPLA-adjuvanted nanoparticles induce significantly strengthened antigen-specific antibody responses, cytokine-secreting splenocytes in the systemic compartment, and higher levels of antigen-specific IgA and IgG in the local mucosa. Meanwhile, significantly expanded lung resident memory (RM) T and B cells (T_RM/B_RM) and alveolar macrophages population are observed in ISCOMs/MPLA-adjuvanted nanoparticle-immunized mice with a 100% survival rate after homogeneous and heterogeneous H3N2 viral challenges. Taken together, ISCOMs/MPLA-adjuvanted protein nanoparticles could improve strong systemic and mucosal immune responses conferring protection in different immunization routes.     

Programmed Nanoparticle‐Loaded Nanoparticles for Deep‐Penetrating 3D Cancer Therapy

Tumors are 3D, composed of cellular agglomerations and blood vessels. Therapies involving nanoparticles utilize specific accumulations due to the leaky vascular structures. However, systemically injected nanoparticles are mostly uptaken by cells located on the surfaces of cancer tissues, lacking deep penetration into the core cancer regions. Herein, an unprecedented strategy, described as injecting “nanoparticle‐loaded nanoparticles” to address the long‐lasting problem is reported for effective surface‐to‐core drug delivery in entire 3D tumors. The “nanoparticle‐loaded nanoparticle” is a silica nanoparticle (≈150 nm) with well‐developed, interconnected channels (diameter of ≈30 nm), in which small gold nanoparticles (AuNPs) (≈15 nm) with programmable DNA are located. The nanoparticle (AuNPs)‐loaded nanoparticles (silica): (1) can accumulate in tumors through leaky vascular structures by protecting the inner therapeutic AuNPs during blood circulation, and then (2) allow diffusion of the AuNPs for penetration into the entire surface‐to‐core tumor tissues, and finally (3) release a drug triggered by cancer‐characteristic pH gradients. The hierarchical “nanoparticle‐loaded nanoparticle” can be a rational design for cancer therapies because the outer large nanoparticles are effective in blood circulation and in protection of the therapeutic nanoparticles inside, allowing the loaded small nanoparticles to penetrate deeply into 3D tumors with anticancer drugs.     

“Dual‐Template” Synthesis of One‐Dimensional Conductive Nanoparticle Superstructures from Coordination Metal–Peptide Polymer Crystals

Bottom‐up fabrication of self‐assembled structures made of nanoparticles may lead to new materials, arrays and devices with great promise for myriad applications. Here a new class of metal–peptide scaffolds is reported: coordination polymer Ag(I)‐DLL belt‐like crystals, which enable the dual‐template synthesis of more sophisticated nanoparticle superstructures. In these biorelated scaffolds, the self‐assembly and recognition capacities of peptides and the selective reduction of Ag(I) ions to Ag are simultaneously exploited to control the growth and assembly of inorganic nanoparticles: first on their surfaces, and then inside the structures themselves. The templated internal Ag nanoparticles are well confined and closely packed, conditions that favour electrical conductivity in the superstructures. It is anticipated that these Ag(I)‐DLL belts could be applied to create long (>100 μm) conductive Ag@Ag nanoparticle superstructures and polymetallic, multifunctional Fe₃O₄@Ag nanoparticle composites that marry the magnetic and conductive properties of the two nanoparticle types.     

Patterning corrosion‐susceptible metallic alloys for digital image correlation in a scanning electron microscope

We investigate the self‐assembly of gold nanoparticles on the surface of magnesium functionalized with 3‐(aminopropyl)trimethoxysilane or 3‐(mercaptopropyl)trimethoxysilane. These nanoparticles served as a speckle pattern for high magnification deformation tracking via digital image correlation combined with scanning electron microscopy. Controlling the pH of the gold nanoparticle suspension to a specific basicity passivated corrosion in magnesium and in three of its alloys to enable proper nanoparticle bonding and self‐assembly. Magnesium was used as a model material as it is particularly difficult to modify for self‐assembly because of its propensity to quickly form a thick oxide, hydroxide, and carbonate layer in the presence of oxygen, water, and carbon dioxide, respectively. Moreover, it corrodes in acidic and slightly basic solutions, further complicating the self‐assembly process. Due to these difficulties, the successful self‐assembly of nanoparticles on magnesium has not previously been reported, to the best of the authors' knowledge. This technique is potentially amendable to other corrosion‐susceptible materials. Gold nanoparticles were self‐assembled in a uniformly dispersed random distribution on pure cast magnesium, cast AM60 (Mg‐6Al‐0.5Mn), rolled WE43 (Mg‐4Y‐3Nd/Gd), and extruded ZE20 (Mg‐2Zn‐0.2Ce).     

Cancer Immunotherapy of TLR4 Agonist–Antigen Constructs Enhanced with Pathogen‐Mimicking Magnetite Nanoparticles and Checkpoint Blockade of PD‐L1

Despite the tremendous potential of Toll‐like receptor 4 (TLR4) agonists in vaccines, their efficacy as monotherapy to treat cancer has been limited. Only some lipopolysaccharides (LPS) isolated from particular bacterial strains or structures like monophosphoryl lipid A (MPLA) derived from lipooligosaccharide (LOS), avoid toxic overactivation of innate immune responses while retaining adequate immunogenicity to act as adjuvants. Here, different LOS structures are incorporated into nanoparticle‐filled phospholipid micelles for efficient vaccine delivery and more potent cancer immunotherapy. The structurally unique LOS of the plant pathogen Xcc is incorporated into phospholipid micelles encapsulating iron oxide nanoparticles, producing stable pathogen‐mimicking nanostructures suitable for targeting antigen presenting cells in the lymph nodes. The antigen is conjugated via a hydrazone bond, enabling rapid, easy‐to‐monitor and high‐yield antigen ligation at low concentrations. The protective effect of these constructs is investigated against a highly aggressive model for tumor immunotherapy. The results show that the nanovaccines lead to a higher‐level antigen‐specific cytotoxic T lymphocyte (CTL) effector and memory responses, which when combined with abrogation of the immunosuppressive programmed death‐ligand 1 (PD‐L1), provide 100% long‐term protection against repeated tumor challenge. This nanovaccine platform in combination with checkpoint inhibition of PD‐L1 represents a promising approach to improve the cancer immunotherapy of TLR4 agonists.     

Precisely Size‐Tunable Monodisperse Hairy Plasmonic Nanoparticles via Amphiphilic Star‐Like Block Copolymers

In situ precision synthesis of monodisperse hairy plasmonic nanoparticles with tailored dimensions and compositions by capitalizing on amphiphilic star‐like diblock copolymers as nanoreactors are reported. Such hairy plasmonic nanoparticles comprise uniform noble metal nanoparticles intimately and perpetually capped by hydrophobic polymer chains (i.e., “hairs”) with even length. Interestingly, amphiphilic star‐like diblock copolymer nanoreactors retain the spherical shape under reaction conditions, and the diameter of the resulting plasmonic nanoparticles and the thickness of polymer chains situated on the surface of the nanoparticle can be readily and precisely tailored. These hairy nanoparticles can be regarded as hard/soft core/shell nanoparticles. Notably, the polymer “hairs” are directly and permanently tethered to the noble metal nanoparticle surface, thereby preventing the aggregation of nanoparticles and rendering their dissolution in nonpolar solvents and the homogeneous distribution in polymer matrices with long‐term stability. This amphiphilic star‐like block copolymer nanoreactor‐based strategy is viable and robust and conceptually enables the design and synthesis of a rich variety of hairy functional nanoparticles with new horizons for fundamental research on self‐assembly and technological applications in plasmonics, catalysis, energy conversion and storage, bioimaging, and biosensors.     

Immune Cell‐Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery

Although tremendous efforts have been made on targeted drug delivery systems, current therapy outcomes still suffer from low circulating time and limited targeting efficiency. The integration of cell‐mediated drug delivery and theranostic nanomedicine can potentially improve cancer management in both therapeutic and diagnostic applications. By taking advantage of innate immune cell's ability to target tumor cells, the authors develop a novel drug delivery system by using macrophages as both nanoparticle (NP) carriers and navigators to achieve cancer‐specific drug delivery. Theranostic NPs are fabricated from a unique polymer, biodegradable photoluminescent poly (lactic acid) (BPLP‐PLA), which possesses strong fluorescence, biodegradability, and cytocompatibility. In order to minimize the toxicity of cancer drugs to immune cells and other healthy cells, an anti‐BRAF V600E mutant melanoma specific drug (PLX4032) is loaded into BPLP‐PLA nanoparticles. Muramyl tripeptide is also conjugated onto the nanoparticles to improve the nanoparticle loading efficiency. The resulting nanoparticles are internalized within macrophages, which are tracked via the intrinsic fluorescence of BPLP‐PLA. Macrophages carrying nanoparticles deliver drugs to melanoma cells via cell–cell binding. Pharmacological studies also indicate that the PLX4032 loaded nanoparticles effectively kill melanoma cells. The “self‐powered” immune cell‐mediated drug delivery system demonstrates a potentially significant advancement in targeted theranostic cancer nanotechnologies.     

Glycocalyx‐Mimicking Nanoparticles for Stimulation and Polarization of Macrophages via Specific Interactions

Malignant tumors develop multiple mechanisms to impair and escape from antitumor immune responses, of which tumor‐associated macrophages that often show immunosuppressive phenotype (M2), play a critical role in tumor‐induced immunosuppression. Therefore, strategies that can reverse M2 phenotype and even enhance immune‐stimulation function of macrophage would benefit tumor immunotherapy. In this paper, self‐assembled glyco‐nanoparticles (glyco‐NPs), as artificial glycocalyx, have been found to be able to successfully induce the polarization of mouse primary peritoneal macrophages from M2 to inflammatory type (M1). The polarization change was evidenced by the decreased expression of cell surface signaling molecules CD206 and CD23, and the increased expression of CD86. Meanwhile, secretion of cytokines supported this polarization change as well. More importantly, this phenomenon is observed not only in vitro, but also in vivo. As far as we known, this is the first report about macrophage polarization being induced by synthetic nanomaterials. Moreover, preparation, characterization of these glyco‐NPs and their interaction with the macrophages are also demonstrated.     

Shedding Light on the Trehalose‐Enabled Mucopermeation of Nanoparticles with Label‐Free Raman Spectroscopy

Nanoparticle‐based drug delivery systems have attracted significant interest owing to their promise as tunable platforms that offer improved intracellular release of cargo therapeutics. However, significant challenges remain in maintaining the physiological stability of the mucosal matrix due to the nanoparticle‐induced reduction in the matrix diffusivity and promotion of mucin aggregation. Such aggregation also adversely impacts the permeability of the nanoparticles, and thus, diminishes the efficacy of nanoparticle‐based formulations. Here, an entirely complementary approach is proposed to the existing nanoparticle functionalization methods to address these challenges by using trehalose, a naturally occurring disaccharide that offers exceptional protein stabilization. Plasmon‐enhanced Raman spectroscopy and far‐red fluorescence emission of the plasmonic silver nanoparticulate clusters are harnessed to create a unique dual‐functional, aggregating, and imaging agent that obviates the need of an additional reporter to investigate mucus–nanoparticle interactions. These spectroscopy‐based density mapping tools uncover the mechanism of mucus–nanoparticle interactions and establish the protective role of trehalose microenvironment in minimizing the nanoparticle aggregation. Thus, in contrast to the prevailing belief, these results demonstrate that nonfunctionalized nanoparticles may rapidly penetrate through mucus barriers, and by leveraging the bioprotectant attributes of trehalose, an in vivo milieu for efficient mucosal drug delivery can be generated.     

Nanoparticle‐Based Manipulation of Antigen‐Presenting Cells for Cancer Immunotherapy

Immunotherapeutic approaches for treating cancer overall have been receiving a considerable amount of interest due to the recent approval of several clinical formulations. Among the different modalities, anticancer vaccination acts by training the body to endogenously generate a response against tumor cells. However, despite the large amount of work that has gone into the development of such vaccines, the near absence of clinically approved formulations highlights the many challenges facing those working in the field. The generation of potent endogenous anticancer responses poses unique challenges due to the similarity between cancer cells and normal, healthy cells. As researchers continue to tackle the limited efficacy of vaccine formulations, fresh and novel approaches are being sought after to address many of the underlying problems. Here the application of nanoparticle technology towards the development of anticancer vaccines is discussed. Specifically, there is a focus on the benefits of using such strategies to manipulate antigen presenting cells (APCs), which are essential to the vaccination process, and how nanoparticle‐based platforms can be rationally engineered to elicit appropriate downstream immune responses.     

Nanoparticle Interactions Guided by Shape‐Dependent Hydrophobic Forces

Self‐assembly of solvated nanoparticles (NPs) is governed by numerous competing interactions. However, relatively little is known about the time‐dependent mechanisms through which these interactions enable and guide the nanoparticle self‐assembly process. Here, using in situ transmission electron microscopy imaging combined with atomistic modeling, it is shown that the forces governing the self‐assembly of hydrophobic nanoparticles change with the nanoparticle shapes. By comparing how gold nanospheres, nanocubes, nanorods, and nanobipyramids assemble, it is shown that the strength of the hydrophobic interactions depends on the overlap of the hydrophobic regions of the interacting nanoparticle surfaces determined by the nanoparticle shapes. Specifically, this study reveals that, in contrast to spherical nanoparticles, where van der Waals forces play an important role, hydrophobic interactions can be more relevant for nanocubes with flat side faces, where an oriented attachment between the nanocubes is promoted by these interactions. The attachment of nanocubes is observed to proceed in two distinct pathways: nanocubes either: (i) prealign their faces before the attachment, or (ii) first connect through a misaligned (edge‐to‐edge) attachment, followed by a postattachment alignment of their faces. These results have important implications for understanding the interaction dynamics of NPs and provide the framework for the design of future self‐assembled nanomaterials.     

Real‐Time Tracking of Superparamagnetic Nanoparticle Self‐Assembly

The spontaneous self‐assembly process of superparamagnetic nanoparticles in a fast‐drying colloidal drop is observed in real time. The grazing‐incidence small‐angle X‐ray scattering (GISAXS) technique is employed for an in situ tracking of the reciprocal space, with a 3 ms delay time between subsequent frames delivered by a new generation of X‐ray cameras. A focused synchrotron beam and sophisticated sample oscillations make it possible to relate the dynamic reciprocal to direct space features and to localize the self‐assembly. In particular, no nanoparticle ordering is found inside the evaporating drop and near‐surface region down to a drop thickness of 90 µm. Scanning through the shrinking drop‐contact line indicates the start of self‐assembly near the drop three‐phase interface, in accord with theoretical predictions. The results obtained have direct implications for establishing the self‐assembly process as a routine technological step in the preparation of new nanostructures.     

A Modular System for the Design of Stimuli‐Responsive Multifunctional Nanoparticle Aggregates by Use of Host–Guest Chemistry

A self‐assembly approach for the design of multifunctional nanomaterials consisting of different nanoparticles (gold, iron oxide, and lanthanide‐doped LiYF₄) is developed. This modular system takes advantage of the light‐responsive supramolecular host–guest chemistry of β‐cyclodextrin and arylazopyrazole, which enables the dynamic and reversible self‐assembly of particles to spherical nanoparticle aggregates in aqueous solution. Due to the magnetic iron oxide nanoparticles, the aggregates can be manipulated by an external magnetic field leading to the formation of linear structures. As a result of the integration of upconversion nanoparticles, the aggregates are additionally responsive to near‐infrared light and can be redispersed by use of the upconversion effect. By varying the nanoparticle and linker concentrations the composition, size, shape, and properties of the multifunctional nanoparticle aggregates can be fine‐tuned.     

Recent Advances in Chemical Synthesis,Self‐Assembly,and Applications of FePt Nanoparticles

This paper reviews recent advances in chemical synthesis, self‐assembly, and potential applications of monodisperse binary FePt nanoparticles. After a brief introduction to nanomagnetism and conventional processes of fabricating FePt nanoparticles, the paper focuses on recent developments in solution‐phase syntheses of monodisperse FePt nanoparticles and their self‐assembly into nanoparticle superlattices. The paper further outlines the surface, structural, and magnetic properties of the FePt nanoparticles and gives examples of three potential applications in data storage, permanent magnetic nanocomposites, and biomedicine.     

Reversible Size‐Tuning of Self‐Assembled Silver Nanoparticles in Phospholipid Membranes via Humidity Control

A monolayer of 5‐nm‐sized Ag nanoparticles embedded in a liquid‐crystalline lipid membrane undergoes a reversible morphological change during hydration and dehydration of the lipid membrane. High mobility of the encapsulating lipid molecules, chemically bound to the Ag atoms, induces redistribution of metal particles to produce significant and optically detectable changes in nanoparticle morphology. The morphological change occurs on a time scale that enables the Ag‐nanoparticle‐embedded membrane to be used as a convenient visual sensor for moisture and other organic solvents, as well as for biosensing by virtue of the biocompatibility of the lipid molecules. The mechanism demonstrated here can also be extended to construct guided nanostructures based on self‐assembled nanoparticles.     

Mesoporous Silica as a Versatile Platform for Cancer Immunotherapy

Immunotherapy has been recognized for decades as a promising therapeutic method for cancer treatment. To enhance host immune responses against cancer, antigen‐presenting cells (APCs; e.g., dendritic cells) or T cells are educated using immunomodulatory agents including tumor‐associated antigens and adjuvants, and manipulated to induce a cascading adaptive immune response targeting tumor cells. Mesoporous silica materials are promising candidates to improve cancer immunotherapy based on their attractive properties that include high porosity, high biocompatibility, facile surface modification, and self‐adjuvanticity. Here, the recent progress on mesoporous‐silica‐based immunotherapies based on two material forms is summarized: 1) mesoporous silica nanoparticles (MSNs), which can be internalized into APCs, and 2) micrometer‐sized mesoporous silica rods (MSRs) that can form a 3D space to recruit APCs. Subcutaneously injected MSN‐based cancer vaccines can be taken up by peripheral APCs or by APCs in lymphoid organs to educate the immune system against cancer cells. MSR cancer vaccines can recruit immune cells into the MSR scaffold to induce cancer‐specific immunity. Both vaccine systems successfully stimulate the adaptive immune response to eradicate cancer in vivo. Thus, mesoporous silica has potential value as a material platform for the treatment of cancer or infectious diseases.     

Mesoporous Silica Nanoparticles Act as a Self‐Adjuvant for Ovalbumin Model Antigen in Mice

Immunization to the model protein antigen ovalbumin (OVA) is investigated using MCM‐41 mesoporous silica nanoparticles as a novel vaccine delivery vehicle and adjuvant system in mice. The effects of amino surface functionalization and adsorption time on OVA adsorption to nanoparticles are assessed. Amino‐functionalized MCM‐41 (AM‐41) shows an effect on the amount of OVA binding, with 2.5‐fold increase in binding capacity (72 mg OVA/g AM‐41) compared to nonfunctionalized MCM‐41 (29 mg OVA/g MCM‐41). Immunization studies in mice with a 10 μg dose of OVA adsorbed to AM‐41 elicits both antibody and cell‐mediated immune responses following three subcutaneous injections. Immunizations at a lower 2 μg dose of OVA adsorbed to AM‐41 particles results in an antibody response but not cell‐mediated immunity. The level of antibody responses following immunization with nanoformulations containing either 2 μg or 10 μg of OVA are only slightly lower than that in mice which receive 50 μg OVA adjuvanted with QuilA, a crude mixture of saponins extracted from the bark of the Quillaja saponaria Molina tree. This is a significant result, since it demonstrates that AM‐41 nanoparticles are self‐adjuvanting and elicit immune responses at reduced antigen doses in vivo compared to a conventional delivery system. Importantly, there are no local or systemic negative effects in animals injected with AM‐41. Histopathological studies of a range of tissue organs show no changes in histopathology of the animals receiving nanoparticles over a six week period. These results establish the biocompatible MCM‐41 silica nanoparticles as a new method for vaccine delivery which incorporates a self‐adjuvant effect.     

A Novel Self‐Assembled Mitochondria‐Targeting Protein Nanoparticle Acting as Theranostic Platform for Cancer

Self‐assembled protein nanoparticles have attracted much attention in biomedicine because of their biocompatibility and biodegradability. Protein nanoparticles have become widely utilized as diagnostic or therapeutic agents for various cancers. However, there are no reports that protein nanoparticles can specifically target mitochondria. This targeting is desirable, since mitochondria are critical in the development of cancer cells. In this study, the discovery of a novel self‐assembled metal protein nanoparticle, designated GST‐MT‐3, is reported, which targets the mitochondria of cancer cells within 30 min in vitro and rapidly accumulates in tumors within 1 h in vivo. The nanoparticles chelate cobalt ions [GST‐MT‐3(Co²⁺)], which induces reactive oxygen species (ROS) production and reduces the mitochondrial membrane potential. These effects lead to antitumor activity in vivo. GST‐MT‐3(Co²⁺) with covalently conjugated paclitaxel synergistically suppress tumors and prolong survival. Importantly, the effective dosage of paclitaxel is 50‐fold lower than that utilized in standard chemotherapy (0.2 vs 10 mg kg^?1). To the best of the authors' knowledge, GST‐MT‐3 is the first reported protein nanoparticle that targets mitochondria. It has the potential to be an excellent platform for combination therapies.     

Spray‐Dried Nanoparticle‐in‐Microparticle Delivery Systems (NiMDS) for Gene Delivery,Comprising Polyethylenimine (PEI)‐Based Nanoparticles in a Poly(Vinyl Alcohol) Matrix

Nucleic acid‐based therapies rely on efficient formulations for nucleic acid protection and delivery. As nonviral strategies, polymeric and lipid‐based nanoparticles have been introduced; however, biological efficacy and biocompatibility as well as poor storage properties due to colloidal instability and their unavailability as ready‐to‐use systems are still major issues. Polyethylenimine is the most widely explored and promising candidate for gene delivery. Polyethylenimine‐based polyplexes and their combination with liposomes, lipopolyplexes, are efficient for DNA or siRNA delivery in vitro and in vivo. In this study, a highly potent spray‐dried nanoparticle‐in‐microparticle delivery system is presented for the encapsulation of polyethylenimine‐based polyplexes and lipopolyplexes into poly(vinyl alcohol) microparticles, without requiring additional stabilizing agents. This easy‐to‐handle gene delivery device allows prolonged nanoparticle storage and protection at ambient temperature. Biological analyses reveal further advantages regarding profoundly reduced cytotoxicity and enhanced transfection efficacies of polyethylenimine‐based nanoparticles from the nanoparticle‐in‐microparticle delivery system over their freshly prepared counterparts, as determined in various cell lines. Importantly, this nanoparticle‐in‐microparticle delivery system is demonstrated as ready‐to‐use dry powder to be an efficient device for the inhalative delivery of polyethylenimine‐based lipopolyplexes in vivo, as shown by transgene expression in mice after only one administration.     

Programmable Negative Differential Resistance Effects Based on Self‐Assembled Au@PPy Core–Shell Nanoparticle Arrays

The negative differential resistance (NDR) effect observed in conducting polymer/Au nanoparticle composite devices is not yet fully clarified due to the random and disordered incorporation of Au nanoparticles into conducting polymers. It remains a formidable challenge to achieve the sequential arrangement of various components in an optimal manner during the fabrication of Au nanoparticle/conducting polymer composite devices. Here, a novel strategy for fabricating Au nanoparticle/conducting polymer composite devices based on self‐assembled Au@PPy core–shell nanoparticle arrays is demonstrated. The interval between the two Au nanoparticles can be precisely programmed by modulating the thickness of the shell and the size of the core. Programmable NDR is achieved by regulating the spacer between two Au nanoparticles. In addition, the Au/conducting polymer composite device exhibits a reproducible memory effect with read–write–erase characteristics. The sequentially controllable assembly of Au@PPy core–shell nanoparticle arrays between two microelectrodes will simplify nanodevice fabrication and will provide a profound impact on the development of new approaches for Au/conducting polymer composite devices.