Compartmentalized Thin Films with Customized Functionality via Interfacial Cross‐linking of Protein Cages

Hybrid thin films with a high loading and homogeneous dispersion of functional nanoparticles (and/or molecules) find applications in (bio)‐sensors and electronic devices. The fabrication of such hybrid thin films, however, suffers from the complex and diverse surface and physicochemical properties of individual nanoparticles. To address this challenge, a facile and general strategy toward compartmentalized thin films through the interfacial cross‐linking of viral protein cages is reported. Employing these protein cages, gold nanoparticles, as well as enzyme horseradish peroxidase, are encapsulated into virus‐like particles and then cross‐linked into thin films with a thickness varying from monolayer to submicron dimensions. These compartmentalized thin films not only ensure that the cargo is homogeneously dispersed, but also display good catalytic activity. This strategy is, in principle, applicable for a wide range of (bio)‐organic nanocontainers, enabling the versatile fabrication of 2D thin films with extensive application prospects.     

Peptide‐Enhanced Selective Surface Deposition of Polymer‐Based Fragrance Delivery Systems

Surface deposition is a critical step in the application of fragrance‐containing products. This contribution presents a novel strategy to enhance the deposition of polymer‐based fragrance delivery systems onto cotton substrates from the application medium using phage display identified peptides. Following the identification of cotton binding peptide ligands under fabric softening conditions via phage display, the strongest binding peptide ligand is incorporated into two model polymer‐based fragrance delivery systems, viz., polymer profragrances and polymer nanoparticles. The model polymer profragrance used is a linear, water soluble poly(N‐(2‐hydroxypropyl)methacrylamide) conjugate, while poly(styrene‐co‐acrylic acid) (PS‐co‐PAA) nanoparticles prepared via miniemulsion polymerization are chosen as the second model system. The incorporation of the cotton binding peptide ligand into these fragrance delivery systems enhances their surface deposition two‐ to three‐fold, as evidenced by fluorescence intensity measurements. In the case of the fragrance‐containing PS‐co‐PAA nanoparticles, the enhanced surface deposition also translates into an increased fragrance release from the cotton surface according to dynamic headspace sampling measurements.     

Facile Nondestructive Assembly of Tyrosine‐Rich Peptide Nanofibers as a Biological Glue for Multicomponent‐Based Nanoelectrode Applications

Achieving the nondestructive assembly of carbon nanoelectrodes with multiple components in a scalable manner enables effective electrical interfaces among nanomaterials. Here, a facile nondestructive multiscale assembly of multicomponent nanomaterials using self‐assembled tyrosine‐rich peptide nanofibers (TPFs) as a biological glue is reported. The versatile functionalities of the rationally devised tyrosine‐rich short peptide allow for (1) self‐assembly of the peptide into nanofibers using noncovalent interactions, followed by (2) immobilization of spatially distributed metal nanoparticles on the nanofiber surface, and (3) subsequent assembly with graphitic nanomaterials into a percolated network‐structure. This percolated network‐structure of silver nanoparticle (AgNP)‐decorated peptide nanofibers with imbedded single‐walled carbon nanotubes (SWNTs) proves to be a versatile nanoelectrode platform with excellent processability. The SWNT–TPF–AgNP assembly, when utilized as a flexible and transparent multicomponent electronic film, was quite effective for enhancing direct electron transfer (DET) as verified for a third‐generation glucose sensor composed of this film. The simple solution process used to produce the functional nanomaterials could provide a new platform for scalable manufacturing of novel nanoelectrode materials forming effective electrical contacts with molecules from diverse biological systems.     

Efficient Synthesis of Carbon Nanotube–Nanoparticle Hybrids

A simple and versatile approach has been developed to synthesize different carbon nanotube (CNT)–nanoparticle hybrid materials. The strategy is based on the nondestructive (noncovalent) functionalization of pristine CNTs and the subsequent in situ synthesis of a variety of different nanoparticles, including metal, semiconductor, and insulator particles, on the modified CNTs. This strategy has been demonstrated here with Pt, CdS, and silica nanoparticles. It is believe that this technique will provide a simple and convenient route to efficiently assemble a wide variety of nanoscale particles/clusters on the surfaces of CNTs, and will enable the construction of nanoscale heterostructures with novel functionalities in nanotechnology.     

Single‐Shot Mesoporous Silica Rods Scaffold for Induction of Humoral Responses Against Small Antigens

Vaccines have shown significant promise in eliciting protective and therapeutic responses. However, most effective vaccines require several booster shots, and it is challenging to generate responses against synthetic molecules and peptides often used to increase target specificity and improve vaccine stability. As continuous antigen uptake and processing by antigen‐presenting cells and persistent toll‐like receptor priming can amplify humoral immunity, it is explored whether a single injection of a mesoporous silica micro‐rod (MSR) vaccine containing synthetic molecules and peptides can generate potent and durable humoral immunity. A single injection of the vaccine targeting a gonadotropin‐releasing hormone (GnRH) decapeptide elicits high anti‐GnRH titer for over 12 months and generated higher titers than bolus or alum formulations. Targeting a Her2/neu peptide within the Trastuzumab binding domain causes immunoreactivity to Her2 on tumor cells and, MSR vaccines against nicotine generated long‐term anti‐nicotine antibodies. A single MSR injection induced germinal center (GC) activity for more than 3 weeks, generated memory B cells, and 7 days of immunostimulation by the vaccine is required to generate effective antibody responses. The MSR vaccine represents a promising technology to bypass the need for multiple immunizations and enhance long‐term antibody production in the context of reproductive biology, cancer, and chronic addiction.     

Poly(2‐(dimethylamino)ethyl methacrylate) Brushes with Incorporated Nanoparticles as a SERS Active Sensing Layer

A simple, fast, and versatile approach to the fabrication of outstanding surface enhanced Raman spectroscopy (SERS) substrates by exploiting the optical properties of the Ag nanoparticles and functional as well as organizational characteristics of the polymer brushes is reported. First, poly(2‐(dimethylamino)ethyl methacrylate) brushes are synthesized directly on glassy carbon by self‐initiated photografting and photopolymerization and thoroughly characterized in terms of their thickness, wettability, morphology, and chemical structure by means of ellipsometry, contact angle, AFM, and XPS, respectively. Second, Ag nanoparticles are homogeneously immobilized into the brush layer, resulting in a sensor platform for the detection of organic molecules by SERS. The surface enhancement factor (SEF) as determined by the detection of Rhodamine 6G is calculated as 6 × 10⁶.     

Hybrid Vesicular Drug Delivery Systems for Cancer Therapeutics

Nanoscale vesicles have provided a versatile platform for the transportation of various types of anticancer and diagnostic agents. Vesicular carriers comprised of liposomes, polymersomes, and peptide‐based vesicles have exhibited potential characteristics for nanomedicine developments. However, the represented systems and current therapeutic approaches to cancers are confronted with serious limitations that hinder their clinical translation. The aforementioned limitations could be minimized by implementing combinatorial hybrid systems. With this method, hybrid vesicular systems can integrate the advantages of several carriers into one structure thereby resulting in an increased therapeutic index and better clinical outcome. The current study has reviewed recently introduced types of hybrid vesicles made of polymer–lipids, polymer–peptides, and lipid–peptides, and its main focus is on multiple metallic‐based nanoparticles incorporated into vesicular carriers to provide theranostic platforms and to boost the efficient cytotoxic effects of the delivered agents.     

Cancer‐Targeted Monodisperse Mesoporous Silica Nanoparticles as Carrier of Ruthenium Polypyridyl Complexes to Enhance Theranostic Effects

Mesoporous silica nanoparticles (MSNs) have been well‐demonstrated as excellent carriers for anticancer drug delivery. Presented here is a cancer‐targeted MSNs drug delivery system that allows the direct fluorescence monitoring of the cellular uptake and localization of theranostic agents in cancer cells. Specifically, the anticancer action mechanisms of RGD peptide‐functionalized MSNs carrying ruthenium polypyridyl complexes (RuPOP@MSNs) are elucidated in detail. RGD peptide surface decoration significantly enhances the cellular uptake of the nanoparticles through receptor‐mediated endocytosis, and increases the selectivity between cancer and normal cells. RuPOP@MSNs exhibits unprecedented enhanced cytotoxicity toward cancer cells overexpressing integrin receptor, which is significantly higher than that of free RuPOP, through induction of apoptosis. The important contribution of extrinsic pathway to cell apoptosis is confirmed by increase in expression levels of death receptors, activation of caspase‐8 and truncation of Bid. The internalized nanoparticles release free RuPOP into the cytoplasm, where they modulate the phosphorylation of p53, AKT, and MAPKs pathways to promote cell apoptosis. Moreover, the strong autofluorescence of RuPOP permits the direct monitoring of drug delivery, and extends the power of theranostics to subcellular level. Taken together, this study provides an effective strategy for the design and development of cancer‐targeted theranostic agents.     

In Situ Enzyme-Induced Self-Assembly of Antimicrobial-Antioxidative Peptides to Promote Wound Healing

Antimicrobial peptides (AMPs) with dual intrinsic antibacterial and antioxidative functions have emerged as promising choice to cure infected wound. However, the most widely applied approach to endow AMPs with antioxidative function is to combine with antioxidative moieties, which may affect the spatial structure and physiological stability of AMPs. Herein, a new type of AMPs with inherent desired stability, antibacterial activity, and reactive oxygen species (ROS) scavenging is developed to effectively heal the infected wound. This formulation is in situ formed at wound site by tyrosinase-triggered oxidation and self-assembly of lyophilized antimicrobial peptide Trp-Arg-Trp-Arg-Trp-Tyr, providing enhanced stability and a fourfold and sevenfold increasement in antibacterial efficiency against E. coli and S. aureus compared to peptide monomers. The antimicrobial peptide is first oxidized and then assembled into nanoparticles. The melanin-like structure has been demonstrated with efficient antioxidant properties, and the experimental data show that peptide nanoparticles to scavenge superoxide radicals, hydroxyl radicals, and H₂O₂. In vivo experiments confirmed that peptide nanoparticles effectively heal infected wounds and obviously reduce ROS. Overall, the research provides a new approach to formulating antimicrobial peptides to treat wound with high healing efficiency.     

A General and Efficient Route to Fabricate Carbon Nanotube‐Metal Nanoparticles and Carbon Nanotube‐Inorganic Oxides Hybrids

Novel pyrenyl‐moieties‐decorated hyperbranched polyglycidol (pHBP) is synthesized and utilized for the functionalization of carbon nanotubes (CNTs) via a non‐covalent (non‐destructive) process. Mediated by a pHBP layer on the CNT sidewall, Au, Ag and Pt nanoparticles and uniform SiO₂, GeO₂ and TiO₂ coatings are generated in situ and deposited onto the as‐prepared CNT/pHBP hybrids, forming versatile homogeneous CNT‐based nanohybrid sols. The coverage of metal nanoparticles and oxide coatings is controllable simply by changing the employed amount of precursors. This easy synthetic strategy provides a general and convenient route to efficiently assemble a wide range of metal nanoparticles and inorganic oxide components on the sidewalls of CNTs, and enables the construction of heterogeneous nanostructures with novel functionalities. As a means of demonstrating the versatility of the fabricated hybrid materials, the catalytic function of CNT/pHBP/Pt hybrids towards the reduction of 4‐nitrophenol and the incorporation of dye molecules into the CNT/pHBP/SiO₂ matrix resulting in fluorescent nanofibers are investigated.     

Strategies for Integrating Metal Nanoparticles with Two-Photon Polymerization Process: Toward High Resolution Functional Additive Manufacturing

This study reports the successful fabrication of complex 3D metal nanoparticle–polymer nanocomposites using two-photon polymerization (2PP). Three complementary strategies are detailed: in situ formation of metal nanoparticles (MeNPs) through a single-step photoreduction process, integration of pre-formed MeNPs into 2PP resin, and site-selective MeNPs decoration of 3D 2PP structures. In the in situ formation strategy, a phase-transfer method is applied to transfer silver and copper ions from an aqueous phase into a toluene solvent to disperse them in photoreactive monomers.The addition of a photosensitive dye, coumarin 30, facilitated the reduction of silver ions and improved the distribution of silver nanoparticles (AgNPs). This strategy is successfully used to produce other MeNPs, such as Cu and Au. The integration of pre-formed MeNPs enabled highly controlled NP size distribution within the 2PP 3D structures with high-fidelity To enable selective decoration of 2PP 3D surfaces with MeNPs, a multimaterial strategy is developed, with one of the resins designed for thiol-ene reaction, which demonstrated selective binding to AuNPs. The successful development of complementary strategies for integration of MeNPs into 2PP resins offers exciting opportunities for fabrication of MeNP composites with sub-micron resolution for applications from photonics to metamaterials and drug delivery.     

Rationally Designed Self‐Assembling Nanoparticles to Overcome Mucus and Epithelium Transport Barriers for Oral Vaccines against Helicobacter pylori

Helicobacter pylori infection is strongly associated with chronic gastritis, peptic ulcers, and gastric cancer. Antibiotic resistance in H. pylori is an increasingly serious threat to global public health. Although oral vaccination is considered to be a promising strategy for protection against H. pylori infection, the poor efficacy of oral vaccines remains a major challenge due to their poor ability to penetrate mucus and cross transepithelial absorption barriers. This study reports the development of a well‐designed nanoparticle that is electrostatically self‐assembled with antigen and cell‐penetrating peptide (CPP), and then coated with a “mucus‐inert” PEG derivative. The nanoparticles have hydrophilic and slightly negative surface properties, which confers excellent mucus‐penetrating ability. Studies demonstrate that the self‐assembled PEG derivatives gradually dissociate from the nanoparticles in mucus, exposing the CPP‐rich cores that are efficiently transepithelial transported via intracellular and paracellular pathways. Nanoparticles containing recombination urease subunit B, a candidate vaccine against H. pylori, significantly enhance systemic and mucosal antibody levels in mice, and these immune responses protect the animals from H. pylori challenge. These results suggest that the CPP‐rich PEGylated nanoparticles may be a powerful platform for building an oral vaccine to protect against gastrointestinal infection by recalcitrant H. pylori or/and other pathogenic microorganisms.     

A Simple and Versatile Pathway for the Synthesis of Visible Light Photoreactive Nanoparticles

This work pioneers the design of visible (415 nm) and UV‐B light (300 nm) reactive nanoparticles via radical polymerization in aqueous heterogeneous media based on methyl methacrylate (MMA) and unique acrylates bearing tetrazole functionalities in a simple and straightforward two step reaction. Stable colloidal nanoparticles with an average diameter of 150 nm and inherent tetrazole functionality (varying from 2.5 to 10 wt% relative to MMA) are prepared via one‐pot miniemulsion polymerization. In a subsequent step, fluorescent pyrazoline moieties serving as linkage points are generated on the nanoparticles by either photoinduced nitrile imine‐mediated tetrazole‐ene cycloaddition (NITEC) or nitrile imine carboxylic acid ligation (NICAL) in water, thus enabling the particles as fluorescent tracers. Through in‐depth molecular surface analysis, it is demonstrated that the photoreactive nanoparticles undergo ligation to a variety of substrates bearing functionalities including maleimides, acrylates, or carboxylic acids, illustrating the versatility of the particle modification process. Critically, the unique ability of the photoreactive nanoparticles to be activated with visible light allows for their decoration with UV light–sensitive molecules. Herein, the ligation of folic acid—a vitamin prone to degradation under UV light—to the photoreactive nanoparticles using visible light is exemplified, demonstrating the synthetic power of our photoreactive fluorescent nanoparticle platform technology.     

Pushing the Functionality of Diamond Nanoparticles to New Horizons: Orthogonally Functionalized Nanodiamond Using Click Chemistry

Click chemistry is one of the most versatile means for the efficient grafting of larger units such as fluorescence labels or biomolecules onto the surface of nanoparticles. Here, a first study on the applicability of different strategies for the copper‐catalyzed azide–alkyne coupling of diamond nanoparticles and organic moieties is reported. Both thermally annealed nanodiamond and mechanically pretreated diamond nanoparticles of different origin can be modified with moieties carrying either azide or alkyne groups. Several organic units have been efficiently “clicked” onto these particles. The method is then applied for the bifunctional surface modification of nanodiamond leading to a material exhibiting carboxylic and alkyne groups at the same time. These can be addressed by orthogonal coupling linkers. A model material carrying two distinct fluorescent dyes is produced this way and shows the characteristic luminescence of both dyes. The findings open the way for the application of nanodiamond as multifunctional labels, drug delivery vehicles, and targeting agents in biomedical applications.     

Carbon Nanoparticles as Versatile Auxiliary Components of Perovskite-Based Optoelectronic Devices

Metal halide perovskite-based optoelectronics has experienced an unprecedented development in the last decade, while further improvements of efficiency, stability, and economic gains of such devices require novel engineering concepts. The use of carbon nanoparticles as versatile auxiliary components of perovskite-based optoelectronic devices is one strategy that offers several advantages in this respect. In this review, first, a brief introduction is offered on metal halide perovskites and on the major performance characteristics of related optoelectronic devices. Then, the versatility and merits of different kinds of carbon nanoparticles, such as graphene quantum dots and carbon dots, are discussed. The tunability of their electronic properties is focused upon, their interactions with perovskite components are analyzed, and different strategies of their implementation in optoelectronic devices are introduced, which include solar cells, light-emitting diodes, luminescent solar concentrators, and photodetectors. It is shown how carbon nanoparticles influence charge carriers extraction and transport, promote perovskite crystallization, allow for efficient passivation, block ion migration, suppress hysteresis, enhance their environmental stability, and thus improve the performance of perovskite-based optoelectronic devices.     

金纳米微粒的光学性质及其在生物成像和光热疗法中的应用

作为生物探针,纳米微粒以其独特的光学性质,易控的表面化学能力,在基于生物成像和诊断的分子生物学和医学领域中引起越来越广泛的关注.贵金属,尤其是金纳米微粒,由于其表面等离子体共振(SPR)等强吸收和发光特性,在生物组织成像,癌症的诊断和治疗中存在着巨大的应用前景.结合配体的金纳米微粒能够特异性地标记癌症细胞上的受体,并提供特定分子的特有信息,进行生物成像和癌症检测.另外,金纳米微粒能够有效地吸收光能量进行局部加热,导致蛋白质变性,并致细胞死亡.主要回顾各种不同尺寸和形状的金纳米微粒的光学特性,以及选择性标记的金纳米微粒在生物成像,癌症诊断和光热疗法中的研究进展.     

Peptide‐Passivated Lead Halide Perovskite Nanocrystals Based on Synergistic Effect between Amino and Carboxylic Functional Groups

A new strategy has been developed using peptides with amino and carboxylic functional groups as passivating ligands to produce methyl ammonium lead bromide (CH₃NH₃PbBr₃) perovskite nanocrystals (PNCs) with excellent optical properties. The well‐passivated PNCs can only be obtained when both amino and carboxylic groups are involved, and this is attributed to the protonation reaction between ? NH₂ and ? COOH that is essential for successful passivation of the PNCs. To better understand this synergistic effect, peptides with different lengths have been studied and compared. Due to the polar nature of peptides, peptide‐passivated PNCs (denoted as PNCs_peptide) aggregate and precipitate from nonpolar toluene solvent, resulting in a high product yield (≈44%). Furthermore, the size of PNCs_peptide can be varied from ≈3.9 to 8.6 nm by adjusting the concentration of the peptide, resulting in tunable optical properties due to the quantum confinement effect. In addition, CsPbBr₃ PNCs are also synthesized with peptides as capping ligands, further demonstrating the generality and versatility of this strategy, which is important for generating high quality PNCs for photonics applications including light‐emitting diodes, optical sensing, and imaging.     

Thiolation and Cell‐Penetrating Peptide Surface Functionalization of Porous Silicon Nanoparticles for Oral Delivery of Insulin

During the last decades, advanced oral delivery systems to enhance the intestinal absorption of widely applicable proteins and peptides, particularly insulin, have been developed. Here, chitosan‐conjugated undecylenic acid‐modified thermally hydrocarbonized porous silicon nanoparticles (CSUn NPs) are used, which promote the mucoadhesion and cellular interactions, thus boosting the intestinal permeability of insulin. Then, to further potentiate the mucoadhesion and permeability enhancement of chitosan‐modified NPs, the surface of the NPs is further modified with either l ‐cysteine (CYS‐CSUn NPs) or a cell‐penetrating peptide (CPP‐CSUn NPs). CYS‐CSUn and CPP‐CSUn NPs show 17‐ and 12‐fold increase in the apparent permeability of insulin across cellular intestinal cells, respectively, with significant enhancement in the cellular interactions. The insulin uptake mechanism pathways in intestinal cells from the developed NPs are also unraveled, which demonstrates major involvement of active transport process and electrostatic interactions, along with adsorptive and clathrin‐mediated endocytic pathways. Moreover, after oral administration in diabetic rats, CYS‐CSUn NPs show 1.86‐ and 2.03‐fold increase in the relative bioavailability of insulin, as compared to empty NPs and oral insulin solution, respectively. In conclusion, this study presents l ‐cysteine modified CSUn NPs as a promising strategy with the ability to overcome the multiple barriers for oral delivery of insulin.     

Printing Patterned Fine 3D Structures by Manipulating the Three Phase Contact Line

The preparation of fine 3D microstructures is an attractive issue; however, it is limited at large‐area fabrication process and fineness morphology manipulation. Here, we propose a strategy to fabricate controllable 3D structures and morphologies from one single droplet via ink‐jet printing. Based on the surface energy difference between the hydrophilic patterns and hydrophobic surface, the three phase contact line of a droplet contained nanoparticles is forced to pin on the patterned hydrophilic points and asymmetrically dewets on the hydrophobic surface, which leads to various morphologies. Through the regulation of pinning patterns and solution properties, the 3D morphology can be well manipulated. This strategy to control the 3D morphology of nanoparticle assembly based on hydrophilic patterns would be of great importance for fabricating controllable 3D structures.     

Calcium Phosphate Mineralized Black Phosphorous with Enhanced Functionality and Anticancer Bioactivity

Biodegradable inorganic nanomaterials have opened new perspectives for cancer therapy due to their inherent anticancer activity. Black phosphorus nanosheets (BPs) with their unique bioactivity have recently been identified as promising cancer therapeutic agents but their application is hampered by the difficulty in surface functionalization. Herein, an in situ calcium phosphate (CaP) mineralization strategy is described to enhance the anticancer activity of BPs. By using BPs as the phosphate sources and growth templates, the synthesized CaP‐mineralized BPs (CaBPs) retain the intrinsic properties of BPs and at the same time have high loading capacities for various fluorophores to enable effective bioimaging and tracing. Compared to BPs, CaBPs exhibit enhanced and selective anticancer bioactivity due to the improved pH‐responsive degradation behavior and intracellular Ca²⁺ overloading in cancer cells. Furthermore, CaBPs specifically target mitochondria and cause structural damage, thus leading to mitochondria‐mediated apoptosis in cancer cells. After intravenous injection, CaBPs target orthotopic breast cancer cells to inhibit tumor growth without giving rise to adverse effects or toxicity. The results demonstrate the great potential of CaBPs as targeted anticancer agents and the CaP mineralization approach provides a versatile surface functionalization strategy for nanotherapeutic agents.