Multimodal Magneto‐Plasmonic Nanoclusters for Biomedical Applications

Multimodal nanostructures can help solve many problems in the biomedical field including sensitive molecular imaging, highly specific therapy, and early cancer detection. However, the synthesis of densely packed, multicomponent nanostructures with multimodal functionality represents a significant challenge. Here, a new type of hybrid magneto‐plasmonic nanoparticles is developed using an oil‐in‐water microemulsion method. The nanostructures are synthetized by self‐assembly of primary 6 nm iron oxide core‐gold shell particles resulting into densely packed spherical nanoclusters. The dense packing of primary particles does not change their superparamagnetic behavior; however, the close proximity of the constituent particles in the nanocluster leads to strong near‐infrared (NIR) plasmon resonances. The synthesis is optimized to eliminate nanocluster cytotoxicity. Immunotargeted nanoclusters are also developed using directional conjugation chemistry through the Fc antibody moiety, leaving the Fab antigen recognizing region available for targeting. Cancer cells labeled with immunotargeted nanoclusters produce a strong photoacoustic signal in the NIR that is optimum for tissue imaging. Furthermore, the labeled cells can be efficiently captured using an external magnetic field. The biocompatible magneto‐plasmonic nanoparticles can make a significant impact in development of point‐of‐care assays for detection of circulating tumor cells, as well as in cell therapy with magnetic cell guidance and imaging monitoring.     

Metal‐Based Nanomaterials in Biomedical Applications: Antimicrobial Activity and Cytotoxicity Aspects

Microbial colonization on material surfaces is ubiquitous. Biofilms derived from surface‐colonized microbes pose serious problems to the society from both an economical perspective and a health concern. Incorporation of antimicrobial nanocompounds within or on the surface of materials, or by coatings, to prevent microbial adhesion or kill the microorganisms after their attachment to biofilms, represents an important strategy in an increasingly challenging field. Over the last decade, many studies have been devoted to preparing meta‐based nanomaterials that possess antibacterial, antiviral, and antifungal activities to combat pathogen‐related diseases. Herein, an overview on the state‐of‐the‐art antimicrobial nanosized metal‐based compounds is provided, including metal and metal oxide nanoparticles as well as transition metal nanosheets. The antimicrobial mechanism of these nanostructures and their biomedical applications such as catheters, implants, medical delivery systems, tissue engineering, and dentistry are discussed. Their properties as well as potential caveats such as cytotoxicity, diminishing efficacy, and induction of antimicrobial resistance of materials incorporating these nanostructures are reviewed to provide a backdrop for future research.     

Electrochromic Switch Devices Mixing Small‐ and Large‐Sized Upconverting Nanocrystals

The hasty progress in smart, portable, flexible, and transparent integrated electronics and optoelectronics is currently one of the driving forces in nanoscience and nanotechnology. A promising approach is the combination of transparent conducting electrode materials (e.g., silver nanowires, AgNWs) and upconverting nanoparticles (UCNPs). Here, electrochromic devices based on transparent nanocomposite films of poly(methyl methacrylate) and AgNWs covered by UCNPs of different sizes and compositions are developed. By combining the electrical control of the heat dissipation in AgNW networks with size‐dependent thermal properties of UCNPs, tunable electrochromic transparent devices covering a broad range of the chromatic diagrams are fabricated. As illustrative examples, devices mixing large‐sized (>70 nm) β‐NaYF₄:Yb,Ln and small‐sized (<15 nm) NaGdF₄:Yb,Ln@NaYF₄ core@shell UCNPs (Ln = Tm, Er, Ce/Ho) are presented, permitting to monitor the temperature‐dependent emission of the particles by the intensity ratio of the Er^{3+ 2}H_11/2 and ⁴S_3/2 → ⁴I_15/2 emission lines, while externally controlling the current flow in the AgNW network. Moreover, by defining a new thermometric parameter involving the intensity ratio of transitions of large‐ and small‐sized UCNPs, a relative thermal sensitivity of 5.88% K^?1 (at 339 K) is obtained, a sixfold improvement over the values reported so far.     

Antimicrobial Ionic Liquid-Based Materials for Biomedical Applications

Excessive and unwarranted administration of antibiotics has invigorated the evolution of multidrug-resistant microbes. There is, therefore, an urgent need for advanced active compounds. Ionic liquids with short-lived ion-pair structures are highly tunable and have diverse applications. Apart from their unique physicochemical features, the newly discovered biological activities of ionic liquids have fascinated biochemists, microbiologists, and medical scientists. In particular, their antimicrobial properties have opened new vistas in overcoming the current challenges associated with combating antibiotic-resistant pathogens. Discussions regarding ionic liquid derivatives in monomeric and polymeric forms with antimicrobial activities are presented here. The antimicrobial mechanism of ionic liquids and parameters that affect their antimicrobial activities, such as chain length, cation/anion type, cation density, and polymerization, are considered. The potential applications of ionic liquids in the biomedical arena, including regenerative medicine, biosensing, and drug/biomolecule delivery, are presented to stimulate the scientific community to further improve the antimicrobial efficacy of ionic liquids.     

Near‐Infrared Photoregulated Drug Release in Living Tumor Tissue via Yolk‐Shell Upconversion Nanocages

Phototrigger‐controlled drug‐release devices (PDDs) can be conveniently manipulated by light to obtain on‐demand release patterns, thereby affording an improved therapeutic efficacy. However, no example of the PDDs has been demonstrated beyond the cellular level to date. By loading 7‐amino‐coumarin derivative caged anticancer drug chlorambucil to yolk–shell structured nanocages possessing upconversion nanophosphors (UCNPs) as moveable core and silica as mesoporous shell, a near‐infrared (NIR)‐regulated PDD is successfully created. In vitro experiments demonstrate that drug release from the PDD could be triggered by continuous‐wave 980 nm light in a controlled pattern. The PDD could be taken up by cancer cells and release the drug to kill cancer cells upon NIR irradiation. Further in vivo studies demonstrate that the PDD can effectively response the NIR stimuli in living tissue. This is the first example of successful NIR‐regulated drug release in living animal model. Such achievement resolves the problem of low tissue penetration depth for traditional PDDs by adopting UCNPs as an NIR light switcher, which gives impetus to practical applications.     

Upconverting Nanoparticle Relays for Resonance Energy Transfer Networks

Networks of fluorophores arranged at the nanoscale can perform basic computation using resonance energy transfer (RET) to transport and manipulate information in the form of excitons. As excitons travel through RET circuits, they are red‐shifted due to vibrational energy loss at each transfer event. This loss prohibits RET circuits from being cascaded to form larger, more computationally complex systems. To address this issue, a nanoassembly capable of converting three or more low energy excitons into a single high energy exciton is designed and fabricated. Deemed the RET relay, this device uses upconverting nanoparticles to achieve anti‐Stokes energy transfer from near‐infrared excited fluorophores to visibly excited fluorophores. In this work, the relay is explored by first breaking it into its halves. Each fluorophore's ability to donate energy to or from the nanoparticle is characterized by a series of photoluminescence experiments. The adsorption of these fluorophores to the particle is modeled as a Langmuir process, revealing the fractional occupancy of each dye that optimizes energy transfer. A fully functional relay is then demonstrated by exciting the near‐infrared dye and extracting the visible dye's fluorescence. Lastly, the performance of the entire construct is optimized over a small sampling of assembly reaction coordinates.     

Magnetically Controllable Silver Nanocomposite with Multifunctional Phosphotriazine Matrix and High Antimicrobial Activity

A recently developed multi‐functional phosphotriazine‐based polymer is used as a matrix for embedding γ‐Fe₂O₃ nanoparticles as well as a suitable chemical template for surface modification with silver nanoparticles. For the primary magnetic modification, maghemite nanoparticles are surface modified with oleic acid in order to render them organophilic and to prevent the aggregation of the nanoparticles. This aggregation could occur as the polymer synthesis, based on reaction of phosphonitrilic chlorine and 1,4‐phenylenediamine, takes place in toluene. The surface active amine units of the polymer structure enable the reduction of silver cations to silver nanoparticles, which are well attached and finely dispersed on its surface. The developed nanocomposite represents one of the few magnetically controllable antibacterial agents based on silver nanoparticles. Magnetic measurements reveal the completely suppressed interactions among maghemite nanoparticles because of their perfect surface coating with an organic surfactant and fine dispersion inside the polymer matrix. This magnetic nanocomposite exhibits a high antibacterial and antifungal activity as proven by tests with nine bacterial strains and four candida (yeast genus) species. For the majority of the tested species, the minimum‐inhibition concentrations are below 100 mg L^?1, which is comparable to their equivalent minimum‐inhibition concentrations in colloidal silver systems.     

Bamboo-Like Nanozyme Based on Nitrogen-Doped Carbon Nanotubes Encapsulating Cobalt Nanoparticles for Wound Antibacterial Applications

In this paper, an artificial nanozyme with efficient oxidase-mimicking activity is developed to investigate antibacterial performance. The bamboo-like nitrogen-doped carbon nanotubes encapsulating cobalt nanoparticles (N-CNTs@Co) are synthesized by pyrolysis of cobalt cyanide cobalt at high temperature. It is found that the oxidase-mimicking activity of N-CNTs@Co is higher than that of iron-centered nanomaterials synthesized by pyrolysis of prussian blue under the same conditions, confirming that the oxidase-mimicking activity is not only related to the active center, but also closely related to its morphology. In addition, the oxidase-mimicking activity of N-CNTs@Co is 12.1 times higher than that of the most reported CeO₂. N-CNTs@Co can catalyze oxygen to produce a large number of reactive oxygen species (ROS) under acidic conditions, resulting in a favorable antibacterial effect against two representative bacteria, Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli). Because the bacterial membrane is damaged by the attack of ROS, the DNA is degraded, eventually causing the bacteria to die. Antibacterial experiments last for 20 days, nevertheless, S. aureus and E. coli do not develop resistance to N-CNTs@Co. The experiments of wound healing in vivo further confirm the high antibacterial efficiency of N-CNTs@Co.     

Aminoglycoside-Based Biomaterials: From Material Design to Antibacterial and Gene Delivery Applications

Aminoglycosides are a family of naturally isolated or chemically semi-synthesized antibiotics consisting of aminocyclitols with several amino and saccharide units. The unique molecule structures render aminoglycosides promising building blocks with high reactivity to perform various non-covalent and covalent reactions, and they are further employed to rationally fabricate versatile materials, such as hydrogels, amphiphiles, hyperbranched polymers, biointerfaces, and nanoparticles. Despite aminoglycosides are widely used in clinics to treat bacterial infections, almost all the efforts are focused on molecular modifications to reduce their toxicities and overcome antibiotic resistance, while their actions as building blocks to construct biomaterials are scarcely discussed. In this feature article, the current progress on the rational design, emergent properties, and promising biological applications of aminoglycoside-based biomaterials are summarized. It is believed that this paper may provide guidance to develop new biomaterials using natural functional molecules as building blocks, and start a new life of aminoglycosides from the view of materials science.     

Ag Nanoparticles Cluster with pH‐Triggered Reassembly in Targeting Antimicrobial Applications

Antibacterial efficiency can be effectively improved by applying targeting antibacterial materials and strategies. Herein, the successful synthesis of uniform pH‐responsive Ag nanoparticle clusters (AgNCs) is demonstrated, which can collapse and reassemble into nonuniform Ag NPs upon exposure to the acidic microenvironment of bacterial infections. This pH triggered reassembly contributes greatly to the improved antibacterial activities of AgNCs against both methicillin‐resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). The minimum inhibitory concentration and minimum bactericidal concentration against MRSA are as low as 4 and 32 µg mL^?1 (which are 8 and 32 µg mL^?1 for E. coli), respectively. In vivo skin wound healing experiments confirm AgNCs can serve as an effective wound dressing to accelerate the healing of MRSA infection. The development of responsive AgNCs offers new materials and strategies in targeting antibacterial applications.     

Synthesis,Structure, Properties,and Applications of Bimetallic Nanoparticles of Noble Metals

Bimetallic nanoparticles of noble metals are of high interest in imaging, biomedical devices, including nanomedicine, and heterogeneous catalysis. Synthesis, properties, characterization, biological properties, and practical applicability of nanoparticles on the basis of platinum group metals and the coin metals Ag and Au are discussed, also in comparison with the corresponding monometallic nanoparticles. In addition to the parameters that are required to characterize monometallic nanoparticles (mainly size, size distribution, shape, crystallographic nature, surface functionalization, charge), further information is required for a full characterization of bimetallic nanoparticles. This concerns the overall elemental composition of a bimetallic nanoparticle population (ratio of the two metals) and the internal distribution of the elements in individual nanoparticles (e.g., the presence of homogeneous alloys, core–shell systems, and possible intermediate stages). It is also important to ensure that all particles are identical in terms of elemental composition, that is, that the homogeneity of the particle population is given. Macroscopic properties like light absorption, antibacterial effects, and catalytic activity depend on these properties. The currently available methods for a full characterization of bimetallic nanoparticles are discussed, and future developments in this field are outlined.     

Multifunctional and Stimuli‐Responsive Polydopamine Nanoparticle‐Based Platform for Targeted Antimicrobial Applications

The rising threat of antimicrobial resistance is a crisis of a global scale. If not addressed, it can lead to health care system problems worldwide. This warrants alternative therapeutic approaches whose mechanism of action starkly differs from conventional antibiotic‐based therapies. Here, a multifunctional and stimuli‐responsive (NIR laser‐activated) antimicrobial platform is engineered by combining the intrinsic photothermal capability and excellent biocompatibility of polydopamine nanoparticles (PdNPs), with the membrane targeting and lytic activities of an antimicrobial peptide (AMP). The resulting PdNP‐AMP nanosystem can specifically target and destabilize the mechanical integrity of the outer membrane of Escherichia coli, as measured using the atomic force microscope. Furthermore, the laser‐induced nano‐localized heating of PdNP—in close proximity to the already compromised bacterial envelope—induces further membrane damage. This results in a more efficient, laser‐activated, bacterial killing action of PdNP‐AMP. The antimicrobial platform developed in this work is shown to be effective against a drug‐resistant E. coli. Overall, this work highlights the advantage and strength of combining multiple and coordinated biocidal mechanisms, into one nanomaterial‐based system and its promise in treating drug‐resistant pathogens.     

Dual Functional Titanium Hydride Particles for Anti-Ultraviolet and Anti-Oxidant Applications

TiO₂ is a typical anti-ultraviolet agent in sunscreen cream, but it suffers from a lack of anti-oxidant activity for scavenging reactive oxygen species. Other traditional sunscreen ingredients, such as C₆₀ and ferulic acid, have moderate antioxidant and UV protection capabilities, and the products do not provide further UV protection. Herein, titanium hydride (TiH_1.97) particles with dual functions of anti-oxidant and anti-ultraviolet are presented as an active material to remove the highly oxidizing and harmful hydroxide free radicals from the skin surface. Owing to the active hydrogen in TiH₂, it shows great potential to eliminate hydroxyl radicals, and the rate is roughly proportional to the exposed surface area (50% /20 min). Together with the biocompatibility of the in situ formed TiO₂, which has a strong ability to absorb ultraviolet light during OH radical scavenging. At the same time, adding titanium hydride to sunscreen also enhances sun protection. The SPF value of sunscreen containing 1% titanium hydride and 20% titanium dioxide can reach 31.8, which exceeds the 20% titanium dioxide (15) by more than twofold. Therefore, titanium hydride with anti-ultraviolet and antioxidant functions can be regarded as a promising and safe ingredient for sunscreen cream.     

Luminescent Ions in Advanced Composite Materials for Multifunctional Applications

Luminescent ions doped materials have been widely applied in many areas, both scientific research and practical fields. Recently, incorporating luminescent ions and advanced materials into versatile and multifunctional systems seems to be a tendency, motivated by the stimulating desires of fundamental studies and technological applications. This feature article provides a general overview of the myriad of luminescent ions‐based advanced composite materials recently investigated. It is demonstrated that the improved or additional properties may be achieved via implementing a strategy of incorporating luminescent ions (lanthanide, transition and main group metal ions) into various types of materials, such as flexible polymers, two‐dimensional atomically thin layers, porous materials, and so on. We outline the design principles, synthesis and processing of various systems joined by luminescent ions doped phosphors. A number of recent works indicate that those novel composite materials allow one to conceive and develop multifunctional applications in a broad area, including optoelectronics, photonics, clean energy, biomedicine, and new types of sensors. Lastly, some challenging issues are discussed and potential directions are suggested for further developing advanced composite materials incorporated with luminescent ions.     

Upconversion Nanoparticles Hybridized Cyanobacterial Cells for Near-Infrared Mediated Photosynthesis and Enhanced Photodynamic Therapy

The hypoxic hallmark of tumor has aroused substantial burdens on a variety of therapeutic modalities including photodynamic therapy (PDT). Recently, biological oxygen evolution enabled by photosynthetic cyanobacterial cells has emerged as one of the most advanced and promising tissue oxygenation strategies, which is particularly beneficial for in situ tumor-PDT. Herein, a near infrared-driven PDT platform based on the photosynthetic cyanobacterial cells hybridized with photosensitizer rose bengal (RB)-loaded upconversion nanoparticles, named as UR-Cyan cells, is reported. Upon the irradiation of 980 nm laser and its upconversions to shorter wavelengths, the formulated UR-Cyan cells are both photosynthetically active for oxygen production and photosensitive for the subsequent singlet oxygen generation by the photosensitizer, resulting in enhanced and sustainable PDT efficacy against tumor cells/tissues. The present design offers a practical approach to conquer the hypoxic burden of PDT operations against a wide range of pathological lesions with excellent biocompatibility and clinical promises.     

Visible and NIR Upconverting Er3+–Yb3+ Luminescent Nanorattles and Other Hybrid PMO‐Inorganic Structures for In Vivo Nanothermometry

Lanthanide‐doped luminescent nanoparticles are an appealing system for nanothermometry with biomedical applications due to their sensitivity, reliability, and minimal invasive thermal sensing properties. Here, four unique hybrid organic–inorganic materials prepared by combining β‐NaGdF₄ and PMOs (periodic mesoporous organosilica) or mSiO₂ (mesoporous silica) are proposed. PMO/mSiO₂ materials are excellent candidates for biological/biomedical applications as they show high biocompatibility with the human body. On the other hand, the β‐NaGdF₄ matrix is an excellent host for doping lanthanide ions, even at very low concentrations with yet very efficient luminescence properties. A new type of Er³⁺–Yb³⁺ upconversion luminescence nanothermometers operating both in the visible and near infrared regime is proposed. Both spectral ranges permit promising thermometry performance even in aqueous environment. It is additionally confirmed that these hybrid materials are non‐toxic to cells, which makes them very promising candidates for real biomedical thermometry applications. In several of these materials, the presence of additional voids leaves space for future theranostic or combined thermometry and drug delivery applications in the hybrid nanostructures.     

Engineering Metal Nanoclusters for Targeted Therapeutics: From Targeting Strategies to Therapeutic Applications

Metal nanoclusters (NCs) have recently attracted great interest in biomedical applications due to their ultrasmall size, good biocompatibility, and unique molecule-like physical and chemical properties. Metal NCs can be rationally designed and integrated with various targeting moieties to achieve unique physicochemical properties and functions. For therapeutic applications, these multifunctional surface-modified NCs can provide distinctive advantages over native metal NCs, such as improved therapeutic effects and reduced side effects. In this review, the design principles of targeting strategies for metal NCs and their composites, including passive and active targeting, and physical and chemical targeting are first discussed. The authors then focus on the recent achievements in the application of metal NCs in targeted therapeutics, including chemotherapy, phototherapy, and radiotherapy. Finally, the authors’ perspectives on the challenges and opportunities of developing metal NCs in targeted therapeutics, further paving their way for potential clinical applications are provided.     

Disulfide‐Bridged Organosilica Frameworks: Designed,Synthesis, Redox‐Triggered Biodegradation,and Nanobiomedical Applications

Over the past few years, silica‐based nanotheranostics have demonstrated their great potential for nano/biomedical applications. However, the uncontrollable and difficult degradability of their pure silica framework and long‐time in vivo retention still cause severe and unpredictable toxicity risks. Therefore, it is highly desirable to design and synthesize materials with safer framework structures and compositions. To this aim, the introduction of disulfide bonds into the silica framework can not only maintain high stability in physiological conditions, but also achieve a stimuli‐responsive biodegradation triggered by intracellular reducing microenvironment in living cells, especially in cancer cells. Once nanotheranostics with disulfide (i.e., thioether)‐bridged silsesquioxane framework are taken up by tumor cells via passive or active targeting, the disulfide bonds in the hybrid silica matrix can be cleaved by a high concentration of intracellular glutathione, enabling redox‐triggered biodegradation of the nanosystems for both concomitant release of the loaded therapeutic cargo and in vivo clearance. It is envisioned that such hybrid materials comprised of disulfide‐bridged silsesquioxane frameworks can become promising responsive and biodegradable nanotheranostics. This review summarizes the recent advances in the synthesis of hybrid organosilicas with disulfide‐bridged silsesquioxane frameworks, and discuss their redox‐triggered biodegradation behaviors combined with their biocompatibility and nanobiomedical applications.     

Pegylated Composite Nanoparticles Containing Upconverting Phosphors and meso‐Tetraphenyl porphine (TPP) for Photodynamic Therapy

The utilization of upconverting nanophosphors (UCNP) for photodynamic therapy (PDT) has gained significant interests due to its ability to convert deep‐penetrating near‐infra red (NIR) light (i.e., 978 nm) to visible light. Previous attempts to co‐localize UCNPs with photosensitizers suffer from low photo­sensitizer loading and problems with nanoparticle aggregation. Here, the preparation of a novel composite nanoparticle formulation comprising 100 nm β?NaYF₄:Yb³⁺,Er³⁺ UCNPs, and meso‐tetraphenyl porphine (TPP) photo­sensitizer, stabilized by biocompatible poly(ethylene glycol‐block‐(dl )lactic acid) block copolymers (PEG‐b‐PLA) is presented. A photosensitizer loading of 10 wt% with respect to UCNP crystal was achieved via the Flash NanoPrecipitation (FNP) process. A sterically stabilizing PEG layer on the composite nanoparticle surface prevents nanoparticle aggregation and ensures nanoparticle stability in water, PBS buffer, and culture medium containing serum proteins, resulting in nanoparticle suitable for in vivo applications. Based on in vitro studies utilizing HeLa cervical cancer cell lines, the composite nanoparticles are shown to exhibit low dark toxicity and efficient cancer cell‐killing activity upon NIR excitation. Exposure with 134 W cm^?2 of 978 nm light for 45 min resulted in 75% HeLa cell death. This is the first quantification of the cell‐killing capabilities of the UCNP/TPP composite nanoparticles formulated for photodynamic therapy.