Recent Advances in Engineering Carriers for siRNA Delivery.

RNA interference (RNAi) technology has been a promising treatment strategy for combating intractable diseases. However, the applications of RNAi in clinical are hampered by extracellular and intracellular barriers. To overcome these barriers, various siRNA delivery systems have been developed in the past two decades. The first approved RNAi therapeutic, Patisiran (ONPATTRO) using lipids as the carrier, for the treatment of amyloidosis is one of the most important milestones. This has greatly encouraged researchers to work on creating new functional siRNA carriers. In this review, the recent advances in siRNA carriers consisting of lipids, polymers, and polymer-modified inorganic particles for cancer therapy are summarized. Representative examples are presented to show the structural design of the carriers in order to overcome the delivery hurdles associated with RNAi therapies. Finally, the existing challenges and future perspective for developing RNAi as a clinical modality will be discussed and proposed. It is believed that the addressed contributions in this review will promote the development of siRNA delivery systems for future clinical applications.

Creation of Chitosan-Based Nanocapsule-in-Nanofiber Structures for Hydrophobic/Hydrophilic Drug Co-Delivery and Their Dressing Applications in Diabetic Wounds.

Nanofiber meshes (NFMs) loaded with therapeutic agents are very often employed to treat hard-to-heal wounds such as diabetic wounds. However, most of the NFMs have limited capability to load multiple or hydrophilicity distinctive-therapeutic agents. The therapy strategy is therefore significantly hampered. To tackle the innate drawback associated with the drug loading versatility, a chitosan-based nanocapsule-in-nanofiber (NC-in-NF) structural NFM system is developed for simultaneous loading of hydrophobic and hydrophilic drugs. Oleic acid-modified chitosan is first converted into NCs by the developed mini-emulsion interfacial cross-linking procedure, followed by loading a hydrophobic anti-inflammatory agent Curcumin (Cur) into the NCs. Sequentially, the Cur-loaded NCs are successfully introduced into reductant-responsive maleoyl functional chitosan/polyvinyl alcohol NFMs containing a hydrophilic antibiotic Tetracycline hydrochloride. Having a co-loading capability for hydrophilicity distinctive agents, biocompatibility, and a controlled release property, the resulting NFMs have demonstrated the efficacy on promoting wound healing either in normal or diabetic rats.

NIR-Cleavable and pH-Responsive Polymeric Yolk-Shell Nanoparticles for Controlled Drug Release.

Responsive drug release and low toxicity of drug carriers are important for designing controlled release systems. Here, a double functional diffractive o-nitrobenzyl, containing multiple electron-donating groups as a crosslinker and methacrylic acid (MAA) as a monomer, was used to decorate upconversion nanoparticles (UCNPs) to produce robust poly o-nitrobenzyl@UCNP nanocapsules using the distillation-precipitation polymerization and templating method. Poly o-nitrobenzyl@UCNP nanocapsules with a robust yolk-shell structure exhibited near-infrared (NIR) light-/pH-responsive properties. When the nanocapsules were exposed to 980 nm NIR irradiation, the loaded drug was efficiently released by altering the shell of the nanocapsules. The photodegradation kinetics of the poly o-nitrobenzyl@UCNP nanocapsules were studied. The anticancer drug, doxorubicin hydrochloride (DOX), was loaded at pH 8.0 with a loading efficiency of 13.2 wt %. The Baker-Lonsdale model was used to determine the diffusion coefficients under different release conditions to facilitate the design of dual-responsive drug release devices or systems. Additionally, cytotoxicity studies showed that the drug release of DOX could be efficiently triggered by NIR to kill cancer cells in a controlled manner.

A Simulation of the Effect of External and Internal Parameters on the Synthesis of a Carbyne with More than 6000 Atoms for Emerging Continuously Tunable Energy Barriers in CNT-Based Transistors.

Transistors made up of carbon nanotube CNT have demonstrated excellent current-voltage characteristics which outperform some high-grade silicon-based transistors. A continuously tunable energy barrier across semiconductor interfaces is desired to make the CNT-based transistors more robust. Despite that the direct band gap of the carbyne inside a CNT can be widely tuned by strain, the size of the carbyne cannot be controlled easily. The production of a monoatomic chain with more than 6000 carbon atoms is an enormous technological challenge. To predict the optimal chain length of a carbyne in different molecular environments, we have developed a Monte Carlo model in which a finite-length carbyne with a size of 4000-15,000 atoms is encapsulated by a CNT at finite temperatures. Our simulation shows that the stability of the carbyne@nanotube is strongly influenced by the nature and porosity of the CNT, the external pressure, the temperature, and the chain length. We have observed an initiation of the chain-breaking process in a compressed carbyne@nanotube. Our work provides much-needed input for optimizing the carbyne length to produce carbon chains much longer than 6000 atoms at ~300 K. Design rules are proposed for synthesizing ~1% strained carbyne@(6,5)CNT as a component in CNT-based transistors to tune the energy barriers continuously.

Highly biocompatible chlorin e6-poly(dopamine) core-shell nanoparticles for enhanced cancer phototherapy.

Cancer is a life-threatening disease worldwide. Although several approaches, such as surgery, chemotherapy, and radiotherapy, have been proven effective for many patients in clinics, they usually suffer from drug resistance, severe toxic-side effects, patient discomfort, and sometimes, unsatisfactory efficacies. In recent years, phototherapy, as a less invasive but effective therapeutic method, has brought hope for cancer treatment. However, most reported photo-therapeutic agents are constructed using complex components with non-negligible toxicity risk, thus retarding the start of their clinical trials. To address this issue, herein, biocompatible photothermal/photodynamic dual-mode therapeutic nanoparticles (CBP NPs) were successfully designed and constructed based on the Food and Drug Administration (FDA)-approved ingredients, chlorin e6 (Ce6) and poly(dopamine) (PDA). Upon light irradiation, hyperthermia was induced and reactive oxygen species (ROS) were generated simultaneously by CBP NPs, contributing to synergistic phototherapy toward cancer. The in vitro and in vivo experiments have demonstrated well the antitumor effect of CBP NPs. More importantly, CBP NPs are completely harmless and degradable in vivo. Together, the CBP NPs developed by us are an ideal candidate for the enhanced phototherapy of tumors, which holds great potential for future clinical translation.

Recent advances in nanotechnology approaches for non-viral gene therapy.

Gene therapy has shown great potential in the treatment of many diseases by downregulating the expression of certain genes. The development of gene vectors as a vehicle for gene therapy has greatly facilitated the widespread clinical application of nucleic acid materials (DNA, mRNA, siRNA, and miRNA). Currently, both viral and non-viral vectors are used as delivery systems of nucleic acid materials for gene therapy. However, viral vector-based gene therapy has several limitations, including immunogenicity and carcinogenesis caused by the exogenous viral vectors. To address these issues, non-viral nanocarrier-based gene therapy has been explored for superior performance with enhanced gene stability, high treatment efficiency, improved tumor-targeting, and better biocompatibility. In this review, we discuss various non-viral vector-mediated gene therapy approaches using multifunctional biodegradable or non-biodegradable nanocarriers, including polymer-based nanoparticles, lipid-based nanoparticles, carbon nanotubes, gold nanoparticles (AuNPs), quantum dots (QDs), silica nanoparticles, metal-based nanoparticles and two-dimensional nanocarriers. Various strategies to construct non-viral nanocarriers based on their delivery efficiency of targeted genes will be introduced. Subsequently, we discuss the cellular uptake pathways of non-viral nanocarriers. In addition, multifunctional gene therapy based on non-viral nanocarriers is summarized, in which the gene therapy can be combined with other treatments, such as photothermal therapy (PTT), photodynamic therapy (PDT), immunotherapy and chemotherapy. We also provide a comprehensive discussion of the biological toxicity and safety of non-viral vector-based gene therapy. Finally, the present limitations and challenges of non-viral nanocarriers for gene therapy in future clinical research are discussed, to promote wider clinical applications of non-viral vector-based gene therapy.

Exciton Luminescence and Optical Properties of Nanocrystalline Cubic Y2O3 Films Prepared by Reactive Magnetron Sputtering.

This paper presents a comprehensive study of the energy structure, optical characteristics, and spectral-kinetic parameters of elementary excitations in a high-purity nanocrystalline cubic Y2O3 film synthesized by reactive magnetron sputtering. The optical transparency gaps for direct and indirect interband transitions were determined and discussed. The dispersion of the refractive index was established based on the analysis of interference effects. It was found that the refractive index of the Y2O3 film synthesized in this study is higher in order of magnitude than that of the films obtained with the help of other technologies. The intrinsic emission of Y2O3 film has been discussed and associated with the triplet-singlet radiative relaxation of self-trapped and bound excitons. We also studied the temperature behavior of the exciton luminescence of Y2O3 for the first time and determined thermal activation barriers. The optical energy and kinetic parameters of cubic Y2O3 films were analyzed in comparison with those of the monoclinic films of yttrium oxide. The main difference between the optical properties of cubic and monoclinic Y2O3 films was established, which allowed for a supposition of their application prospects.

Deep-Brain Three-Photon Imaging Enabled by Aggregation-Induced Emission Luminogens with Near-Infrared-III Excitation.

Understanding the morphology and hemodynamics of cerebral vasculature at large penetration depths and microscale resolution is fundamentally important to decipher brain diseases. Among the various imaging technologies, three-photon (3P) microscopy is of significance by virtue of its deep-penetrating capability and submicron resolution, which especially benefits in vivo vascular imaging. Aggregation-induced emission luminogens (AIEgens) have been recognized to be extraordinarily powerful as 3P probes. However, systematic studies on the structure-performance relationship of 3P AIEgens have been seldom reported. Herein, a series of AIEgens has been designed and synthesized. By intentionally introducing benzene rings onto electron donors (D) and acceptors (A), the molecular distortion, conjugation strength, and the D-A relationship can be facilely manipulated. Upon encapsulation with DSPE-PEG2000, the optimized AIEgens are successfully applied for 3P microscopy with emission in the far-red/near-infrared-I (NIR-I, 700-950 nm) region under the near-infrared-III (NIR-III, 1600-1870 nm) excitation. Impressively, using mice with an opened skull, vasculature within 1700 µm and a microvessel with a diameter of 2.2 µm in deep mouse brain were clearly visualized. In addition, the hemodynamics of blood vessels were well-characterized. Thus, this work not only proposes a molecular design strategy of 3P AIEgens but also promotes the performance of 3P imaging in cerebral vasculature.

A biocompatible photosensitizer with a high intersystem crossing efficiency for precise two-photon photodynamic therapy.

Photodynamic efficiency is strongly dependent on the generation rate of reactive oxygen species (ROS) and the tissue penetration depth. Recent advances in materials science reveal that organic molecules with room-temperature phosphorescence (RTP) can potentially serve as efficient photosensitizers owing to their limited dark cytotoxicity and abundant triplet excitons upon light irradiation. In this study, we combine RTP materials with two-photon excitation to improve the ROS generation, therapeutic precision, and tissue penetration of photodynamic therapy. We successfully prepared a novel RTP-based photosensitizer (BF2DCz) with a high photoluminescence quantum yield of 47.7 ± 3% and a remarkable intersystem crossing efficiency of ∼90.3%. By encapsulation into the bovine serum albumin (BSA) matrix, BF2DCz-BSA exhibits excellent biocompatibility, negligible dark toxicity, and superior photostability. Excitation using a femtosecond laser causes BF2DCz-BSA to efficiently generate ROS and precisely exert cell damage at the desired location.

Organic/Inorganic Self-Assembled Hybrid Nano-Architectures for Cancer Therapy Applications.

Since the conceptualization of nanomedicine, numerous nanostructure-mediated drug formulations have progressed into clinical trials for treating cancer. However, recent clinical trial results indicate such kind of drug formulations has a limited improvement on the antitumor efficacy. This is due to the biological barriers associated with those formulations, for example, circulation stability, extravasation efficiency in tumor, tumor penetration ability, and developed multi-drug resistance. When employing for nanomedicine formulations, pristine organic-based and inorganic-based nanostructures have their own limitations. Accordingly, organic/inorganic (O/I) hybrids have been developed to integrate the merits of both, and to minimize their intrinsic drawbacks. In this context, the recent development in O/I hybrids resulting from a self-assembly strategy will be introduced. Through such a strategy, organic and inorganic building blocks can be self-assembled via either chemical covalent bonds or physical interactions. Based on the self-assemble procedure, the hybridization of four organic building blocks including liposomes, micelles, dendrimers, and polymeric nanocapsules with five functional inorganic nanoparticles comprising gold nanostructures, magnetic nanoparticles, carbon-based materials, quantum dots, and silica nanoparticles will be highlighted. The recent progress of these O/I hybrids in advanced modalities for combating cancer, such as, therapeutic agent delivery, photothermal therapy, photodynamic therapy, and immunotherapy will be systematically reviewed.

Development of poly(vinyl alcohol)/starch/ethyl lauroyl arginate blend films with enhanced antimicrobial and physical properties for active packaging.

Active packaging films have emerged as alternatives to replace petroleum-based packaging materials. In this work, poly(vinyl alcohol) (PVA)/starch/ethyl lauroyl arginate (LAE) films possessing enhanced properties were prepared. Scanning electron microscopy (SEM) showed that PVA and starch were compatible, the concentrations of LAE greatly affected the structural integrity. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction showed that the inclusion of LAE did not significantly affect the intermolecular interactions and crystal structures of the polymer matrix. With an increase of the LAE content, the tensile strength (TS) was slightly decreased due to the altered microstructures, the elongation at break (EB) significantly increased ascribed to the synergistic effect of acetic acid, glycerol and LAE. The values of TS and EB were 17.25 MPa and 586.08%, respectively when LAE was 10%. Active films showed good barrier properties from UV while retaining the transmittance in the visible light region. The films containing 1% of LAE exhibited antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), the inhibition zone of bacterial growth gradually expanded with increasing LAE content. This study demonstrates the potential of using LAE as the antibacterial agent for synthesizing natural-based polymeric films for active packaging applications.

Metal organic framework-coated gold nanorod as an on-demand drug delivery platform for chemo-photothermal cancer therapy.

Chemo-photothermal therapy based on nanoparticles has emerged as a promising strategy for cancer treatment. However, its therapeutic efficacy and application potential are largely subjected to the uncontrollability and biotoxicity of functional nanoplatforms. Herein, a novel biocompatible and biodegradable metal organic framework (MOF), which was constructed by growing crystalline zeolitic imidazolate framework-8 on gold nanoroad (Au@ZIF-8), was designed and fabricated for efficient drug loading and controlled release. Owing to the large surface area and guest-matching pore size of ZIF-8, doxorubicin (DOX) was successfully loaded into the Au@ZIF-8 with a high drug loading efficiency of ~ 37%. Under NIR light or weakly acidic environment, the ZIF-8 layer was quickly degraded, which resulted in an on-demand drug release in tumour site. More importantly, under the irradiation of near infrared (NIR) laser, highly efficient cancer treatment was achieved in both in vitro cell experiment and in vivo tumour-bearing nude mice experiment due to the synergistic effect of photothermal (PTT) therapy and chemotherapy. In addition, the in vivo study revealed the good biocompatibility of Au@ZIF-8. This work robustly suggested that Au@ZIF-8 could be further explored as a drug delivery system for chemo-photothermal synergistic therapy.

Seawater Desalination by Interfacial Solar Vapor Generation Method Using Plasmonic Heating Nanocomposites.

With the ever-growing demand in fresh water supply, great efforts have been devoted to developing sustainable systems which could generate fresh water continuously. Solar vapor generation is one of the promising strategies which comprise an unlimited energy source and efficient solar-to-heat generators for overcoming fresh water scarcity. However, current solar vapor generation systems suffer either from inefficient utilization of solar energy or an expensive fabrication process. In this paper, we introduced a nano-plasmonic approach, i.e., a floatable nanocompoiste where copper sulfide nanorods (Cu2-xS NRs) are embedded in a polyvinyl alcohol (PVA) matrix, for solar-to-vapor generation. A high solar vapor generation efficiency of ~87% and water evaporation rate of 1.270 kg m-2 h-1 were achieved under simulated solar irradiation of 1 sun. With the illumination of natural daylight, seawater was purified using Cu2-xS NRs-PVA gel, with high purity, as distilled drinking water. The plasmonic nanocomposites demonstrated here are easy to fabricate and highly efficient for solar vapor generation, illustrating a potential solution for future seawater desalination.

Biodegradable Polymers for Gene-Delivery Applications.

Gene-based therapies have emerged as a new modality for combating a myriad of currently incurable diseases. However, the fragile nature of gene therapeutics has significantly hampered their biomedical applications. Correspondingly, the development of gene-delivery vectors is of critical importance for gene-based therapies. To date, a variety of gene-delivery vectors have been created and utilized for gene delivery. In general, they can be categorized into viral- and non-viral vectors. Due to safety issues associated with viral vectors, non-viral vectors have recently attracted much more research focus. Of these non-viral vectors, polymeric vectors, which have been preferred due to their low immunogenicity, ease of production, controlled chemical composition and high chemical versatility, have constituted an ideal alternative to viral vectors. In particular, biodegradable polymers, which possess advantageous biocompatibility and biosafety, have been considered to have great potential in clinical applications. In this context, the aim of this review is to introduce the recent development and progress of biodegradable polymers for gene delivery applications, especially for their chemical structure design, gene delivery capacity and additional biological functions. Accordingly, we first define and categorize biodegradable polymers, followed by describing their corresponding degradation mechanisms. Various types of biodegradable polymers resulting from natural and synthetic polymers will be introduced and their applications in gene delivery will be examined. Finally, a future perspective regarding the development of biodegradable polymer vectors will be given.

Aqueous Phase Synthesis of Cu2-x S Nanostructures and Their Photothermal Generation Study.

Size- and shape-dependent features of plasmonic nanocrystals govern the development of their applications. In the past decades, gold nanostructures, such as gold nanorods and nanoshells, have been well studied and applied for sensing, bioimaging, and photothermal generation. However, knowledge of copper chalcogenide, a new generation of plasmonic nanomaterials, is limited, especially about their preparation and size- and shape-dependent photothermal properties. In this work, controllable size and shape Cu2-x S nanocrystals (NCs) are synthesized by a facile aqueous route. Using low-molecular-weight polyethylenimine (PEI) as the reducing and capping agents, the size and shape of Cu2-x S NCs can be controlled with lengths from 6.5 to 46.5 nm and the aspect ratio from 2.2 to 7.5 by adjusting the concentration of PEI. The plasmonic peak of Cu2-x S experiences a redshift (from 1145 to 1369 nm) when the length increases from 6.5 to 44.5 nm. Under the irradiation of 1064 nm laser with 1.33 W/cm2, an excellent photothermal conversion rate (from 34.9 to 49.0%) is obtained. The characterization of Cu2-x S NCs is conducted with a UV-vis spectrometer, transmission electron microscopy, powder X-ray diffraction measurements, and 1064 nm laser.

Development of Direct-Laser-Printable Light-Powered Nanocomposites.

Four-dimensional (4D) printable light-powered materials have emerged as a new generation of materials for the development of functional devices. The design of these types of materials is mostly based on the trans-cis transformation of azobenzene moieties in a liquid crystalline elastomer (LCE) matrix, in which the motion is triggered by ultraviolet (UV) irradiation. In this paper, we first report on a direct laser printable photoresist for producing light-powered 4D structures with enhanced mechanical properties and near-infrared (NIR) responsive mechanical deformation. The reported nanocomposite design is based on the photothermal effects of gold nanorods (AuNRs), which can induce the nematic-to-isotropic transition of LCE upon exposure to NIR irradiation. The miscibility between AuNRs and LCE is enhanced by thiol functionalization. Appropriate printing parameters are determined, and nanocomposites containing 0-3 wt % of AuNR loading are fabricated via femtosecond two-photon direct laser writing. The effects of the AuNR loading fraction and laser power on the light-powered actuating performance are evaluated. It is found that the nanocomposite with AuNR loading of 3 wt % demonstrates the maximum percentage (20%) of elongation under an NIR laser power of 2 W. An increase in laser power can lead to faster deformation but slower restoration. The nanocomposites demonstrate relatively good stability. Even after 300 actuation cycles, 80% of the elongation magnitude can be retained. In addition, an improvement of 80% in the complex modulus of the nanocomposites, due to the inclusion of AuNRs, is observed.

Wearable Fluid Capture Devices for Electrochemical Sensing of Sweat.

Wearable sensing technologies are vital for realizing personalized health monitoring. Noninvasive human sweat sampling is essential for monitoring an individual's physical state using rich physiological data. However, existing wearable sensing technologies lack the controlled capture of body sweat and in performing on-device measurement without inflammatory contact. Herein, we report the development of a wearable sweat-capture device using patterned graphene arrays with controlled superwettability and electrical conductivity for simultaneously capturing and electrochemically measuring sweat droplets. The sweat droplets exhibited strong attachment on the superhydrophilic graphene patterns, even during moderate exercising. The captured sweat droplets present strong electrochemical signals using graphene films as the working electrode and metal pins as the counter electrode arrays assembled on 3D printed holders, at the detection limit of 6 µM for H2O2 sensing. This research enables full-body spatiotemporal mapping of sweat, which is beneficial for a broad range of personalized monitoring applications, such as drug abuse detection, athletics performance optimization, and physiological wellness tracking.

Intensifying the Antimicrobial Activity of Poly[2-( tert-butylamino)ethyl Methacrylate]/Polylactide Composites by Tailoring Their Chemical and Physical Structures.

Poly[2-( tert-butylaminoethyl) methacrylate] (PTA), an important class of antimicrobial polymers, has demonstrated its great biocidal efficiency, favorable nontoxicity, and versatile applicability. To further enhance its antimicrobial efficiency, an optimization of the chemical structure of PTA polymers is performed via atom transfer radical polymerization (ATRP) in terms of the antimicrobial ability against Escherichia coli ( E. coli) and Staphylococcus aureus ( S. aureus). After the optimization, the resulting PTA is blended into a polylactide (PLA) matrix to form PTA/PLA composite thin films. It is first found, that the antimicrobial efficiency of PTA/PLA composites was significantly enhanced by controlling the PLA crystallinity and the PLA spherulite size. A possible mechanistic route regarding this new finding has been rationally discussed. Lastly, the cytotoxicity and mechanical properties of a PTA/PLA composite thin film exhibiting the best biocidal effect are evaluated for assessing its potential as a new material for creating antimicrobial biomedical devices.

Effects of Cd-based Quantum Dot Exposure on the Reproduction and Offspring of Kunming Mice over Multiple Generations.

The potential health risks associated with heavy-metal containing quantum dots (QDs) are a major concern accompanying their increased application in both research and industry. In this contribution, we investigate the effects of QDs on reproductive outcomes in Kunming mice across three generations. Rather than being exposed to QDs during pregnancy, mice were intravenously injected with phospholipid micelle encapsulated CdSe/CdS/ZnS QDs at a dosage of 0.81 mg Cd/kg two weeks before mating. Four treatment groups were studied: non-injected control, female injected, male injected and both parents injected with QDs. Although QDs accumulated in the major organs of treated mice, we did not detect any pregnancy complications or adverse effects. No significant difference in pregnancy outcomes could be identified between the QD treated groups and the control group. More importantly, through behavior monitoring, blood tests and histological evaluations, two generations of the offspring were observed to be in normal and healthy condition. Our results show that QD exposure with a short buffering period before conception does not cause obvious pregnancy complications or significant toxicity effects in treated mice or their offspring. This indicates that a short buffering period after QD exposure may reduce potential risk of QDs to reproductive health.

Hyper-elastic modeling and mechanical behavior investigation of porous poly-D-L-lactide/nano-hydroxyapatite scaffold material.

Poly-D-L-lactide/nano-hydroxyapatite (PDLLA/nano-HA) can be used as the biological scaffold material in bone tissue engineering as it can be readily made into a porous composite material with excellent performance. However, constitutive modeling for the mechanical response of porous PDLLA/nano-HA under various stress conditions has been very limited so far. In this work, four types of fundamental compressible hyper-elastic constitutive models were introduced for constitutive modeling and investigation of mechanical behaviors of porous PDLLA/nano-HA. Moreover, the unitary expressions of Cauchy stress tensor have been derived for the PDLLA/nano-HA under uniaxial compression (or stretch), biaxial compression (or stretch), pure shear and simple shear load by using the theory of continuum mechanics. The theoretical results determined from the approach based on the Ogden compressible hyper-elastic constitutive model were in good agreement with the experimental data from the uniaxial compression tests. Furthermore, this approach can also be used to predict the mechanical behaviors of the porous PDLLA/nano-HA material under the biaxial compression (or stretch), pure shear and simple shear.