Biocompatible Nanostructures Research Articles

Green Synthesis of Silver Nanoparticles Using Pecan Nut (Carya illinoinensis) Shell Extracts and Evaluation of Their Antimicrobial Activity.

Nowadays, the increase in bacteria resistant to multiple antibiotics has become a real threat to the human health, forcing researchers to develop new strategies. Silver nanoparticles (AgNPs) may be a viable solution to this problem. The green synthesis of AgNPs is considered a green, ecological and low-priced process that provides small and biocompatible nanostructures with antimicrobial activity with a potential application in medicine. In this work, pecan nut shell extracts were analyzed in order to determine their viability for the production of AgNPs. These NPs were synthesized using an extract rich in bioactive molecules, varying the reaction time and silver nitrate (AgNO3) concentration. AgNPs production was confirmed by FT-IR, UV-Vis and EDX spectroscopy, while their morphology and size were determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The antibacterial activity of AgNPs was evaluated by the agar diffusion method against Salmonella typhi, Staphylococcus aureus and Proteus mirabilis. The results showed that it is possible to obtain nanoparticles from an extract rich in antioxidant molecules with a size between 39.9 and 98.3 nm with a semi-spherical morphology. In addition, it was shown that the reaction time and the concentration of the precursor influence the final nanoparticles size. Antimicrobial tests showed that there is greater antimicrobial inhibition against Gram-negative than Gram-positive microorganisms, obtaining inhibition zone from 0.67 to 5.67 mm.

Polysaccharide Layer-by-Layer Coating for Polyimide-Based Neural Interfaces.

Implantable flexible neural interfaces (IfNIs) are capable of directly modulating signals of the central and peripheral nervous system by stimulating or recording the action potential. Despite outstanding results in acute experiments on animals and humans, their long-term biocompatibility is hampered by the effects of foreign body reactions that worsen electrical performance and cause tissue damage. We report on the fabrication of a polysaccharide nanostructured thin film as a coating of polyimide (PI)-based IfNIs. The layer-by-layer technique was used to coat the PI surface due to its versatility and ease of manufacturing. Two different LbL deposition techniques were tested and compared: dip coating and spin coating. Morphological and physiochemical characterization showed the presence of a very smooth and nanostructured thin film coating on the PI surface that remarkably enhanced surface hydrophilicity with respect to the bare PI surface for both the deposition techniques. However, spin coating offered more control over the fabrication properties, with the possibility to tune the coating’s physiochemical and morphological properties. Overall, the proposed coating strategies allowed the deposition of a biocompatible nanostructured film onto the PI surface and could represent a valid tool to enhance long-term IfNI biocompatibility by improving tissue/electrode integration.

Gelatin‐Lysozyme Nanofibrils Electrospun Patches with Improved Mechanical, Antioxidant, and Bioresorbability Properties for Myocardial Regeneration Applications

AbstractBiopolymeric patches show enormous potential for the regeneration of infarcted myocardium tissues. However, most of them usually lack appropriate mechanical performance, stability in water, and important functionalities; for instance, antioxidant activity. Protein nanofibrils, such as lysozyme nanofibrils (LNFs), are biocompatible nanostructures with excellent mechanical performance, water insolubility, and antioxidant activity exploited to fabricate materials for different biomedical applications. In this study, LNFs are used to produce gelatin electrospun nanocomposite cardiac patches with improved properties. The addition of the LNFs to the gelatin electrospun patches enhance their mechanical properties, increasing the patches Young's modulus from 3 to 6 MPa, in their wet state, which agrees with the requirements of myocardial contractility. Additionally, it is observed an increment of the antioxidant activity to 80%, by adding only 5% (w/w) of LNFs, and the bioresorbability rate is shortened to 30–35 d, compared to 45 d for the gelatin‐only patches, while maintaining their morphology, and biocompatibility toward cardiomyoblasts and fibroblasts. Furthermore, 15% of a model drug is burst released from the patches and preserved for 21 d. Overall, these results demonstrate that LNFs have a great potential as functional reinforcements to fabricate biopolymeric electrospun patches for myocardial infarcted tissue regeneration.

Enhancement of Biofunctionalization by Loading Manuka Oil on TiO2 Nanotubes.

Metallic implants (mesh) for guided bone regeneration can result in foreign body reactions with surrounding tissues, infection, and inflammatory reactions caused by micro-organisms in the oral cavity after implantation. This study aimed to reduce the possibility of surgical failure caused by microbial infection by loading antibacterial manuka oil in a biocompatible nanostructure surface on Ti and to induce stable bone regeneration in the bone defect. The manuka oil from New Zealand consisted of a rich β-triketone chemotype, leptospermone, which showed strong inhibitory effects against several bacteria, even at very low oil concentrations. The TiO2 nanotubular layer formed by anodization effectively enhanced the surface hydrophilicity, bioactivity, and fast initial bone regeneration. A concentration of manuka oil in the range of 0.02% to less than 1% can have a synergistic effect on antibacterial activity and excellent biocompatibility. A manuka oil coating (especially with a concentration of 0.5%) on the TiO2 nanotube layer can be expected not only to prevent stenosis of the connective tissue around the mesh and inflammation by microbial infection but also to be effective in stable and rapid bone regeneration.

Primary attempt towards bioapplicability of one-dimensional high entropy alloys

Recent efforts on increasing the multi-functionality of high entropy alloys are receiving significant attention. Though HEA systems are being explored as biomaterials in its bulk form, downsizing them to nanoscale and engineering them for biological applications remains not attempted. Here one-dimensional Fe-Co-Ni-Cu-Zn high entropy alloy nanowires (NWs) are reported as biocompatible nanostructures and primary attempts have been made towards their therapeutic applications. These Fe-Co-Ni-Cu-Zn NWs are a new family of HEAs containing both magnetic and non-magnetic elements, showed good biocompatibility ∼ 80% cell viability and noteworthy photothermal therapy (PTT) mediated cell efficacy that can open new avenues and introduce novel family alloys as bio-HEA nanostructures.

Microemulsion Based Nanostructures for Drug Delivery

Most of the active pharmaceutical compounds are often prone to display low bioavailability and biological degradation represents an important drawback. Due to the above, the development of a drug delivery system (DDS) that enables the introduction of a pharmaceutical compound through the body to achieve a therapeutic effect in a controlled manner is an expanding application. Henceforth, new strategies have been developed to control several parameters considered essential for enhancing delivery of drugs. Nanostructure synthesis by microemulsions (ME) consist of enclosing a substance within a wall material at the nanoscale level, allowing to control the size and surface area of the resulting particle. This nanotechnology has shown the importance on targeted drug delivery to improve their stability by protecting a bioactive compound from an adverse environment, enhanced bioavailability as well as controlled release. Thus, a lower dose administration could be achieved by minimizing systemic side effects and decreasing toxicity. This review will focus on describing the different biocompatible nanostructures synthesized by ME as controlled DDS for therapeutic purposes.

Potential Use of Nitrogen-Doped Carbon Nanotube Sponges as Payload Carriers Against Malignant Glioma.

Glioblastoma is the most aggressive brain tumor with a low median survival of 14 months. The only Food and Drug Administration (FDA)-approved treatment for topical delivery of the cancer drug carmustine is Gliadel. However, its use has been associated with several side-effects, mainly provoked by a mass effect. Nitrogen-doped carbon nanotube sponges (N-CNSs) are a new type of nanomaterial exhibiting high biocompatibility, and they are able to load large amounts of hydrophobic drugs, reducing the amount of carriers. This study evaluated the use of N-CNSs as potential carmustine carriers using malignant glioma cell lines. N-CNSs were characterized by nanoparticle tracking analysis and transmission electron microscopy. The biocompatibility of N-CNSs was determined in glioma cell lines and in primary astrocytes. Afterward, N-CNSs were loaded with carmustine (1:10 w/w), and the drug and liberation efficiency, as well as cytotoxicity induction, were determined. N-CNSs presented a homogeneous size distribution formed by round nanotubes, without induced cytotoxicity, at concentrations below 40 µg/mL. The N-CNSs loaded with carmustine exhibited a continuous kinetic release of carmustine with a maximum release after 72 h. The cytotoxic effect of N-CNSs loaded with carmustine was similar to that of carmustine alone. The results demonstrated that N-CNSs are a biocompatible nanostructure that could be used as carriers for the tumoral load of large amounts of chemotherapeutic agents.

Green Synthesized Silver Nanoparticles: Antibacterial and Anticancer Activities, Biocompatibility, and Analyses of Surface-Attached Proteins.

The increasing number of multi-drug-resistant bacteria and cancer cases, that are a real threat to humankind, forces research world to develop new weapons to deal with it. Biogenic silver nanoparticles (AgNPs) are considered as a solution to this problem. Biosynthesis of AgNPs is regarded as a green, eco-friendly, low-priced process that provides small and biocompatible nanostructures with antimicrobial and anticancer activities and potential application in medicine. The biocompatibility of these nanoparticles is related to the coating with biomolecules of natural origin. The synthesis of AgNPs from actinobacterial strain was confirmed using UV-Vis spectroscopy while their morphology, crystalline structure, stability, and coating were characterized using, transmission electron microscopy (TEM), X-ray diffraction (XRD), Zeta potential and Fourier transform infrared spectroscopy (FTIR). Antibacterial activity of biogenic AgNPs was evaluated by determination of minimum inhibitory and minimum biocidal concentrations (MIC and MBC) against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. The potential mechanism of antibacterial action of AgNPs was determined by measurement of ATP level. Since the use of AgNPs in biomedical applications depend on their safety, the in vitro cytotoxicity of biosynthesized AgNPs on MCF-7 human breast cancer cell line and murine macrophage cell line RAW 264.7 using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, cell lactate dehydrogenase (LDH) release and measurement of reactive oxygen species (ROS) level were assessed. The nanoparticle protein capping agent that can be involved in reduction of silver ions to AgNPs and their stabilization was identified using LC-MS/MS. Nanoparticles were spherical in shape, small in size (mean 13.2 nm), showed crystalline nature, good stability (−18.7 mV) and presence of capping agents. They exhibited antibacterial activity (MIC of 8–128 μg ml−1, MBC of 64–256 μg ml−1) and significantly decreased ATP levels in bacterial cells after treatment with different concentrations of AgNPs. The in vitro analysis showed that the AgNPs demonstrated dose-dependent cytotoxicity against RAW 264.7 macrophages and MCF-7 breast cancer cells but higher against the latter than the former. Cell viability decrease was found to be 42.2–14.2 and 38.0–15.5% while LDH leakage 14.6–42.7% and 19.0–45.0%, respectively. IC50 values calculated for MTT assay was found to be 16.3 and 12.0 μg ml−1 and for LDH assay 102.3 and 76.2 μg ml−1, respectively. Moreover, MCF-7 cells released a greater amount of ROS than RAW 264.7 macrophages during stimulation with all tested concentrations of AgNPs (1.47–3.13 and 1.02–2.58 fold increase, respectively). The SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) analysis revealed the presence of five protein bands at a molecular weight between 31.7 and 280.9 kDa. These proteins showed the highest homology to hypothetical proteins and porins from E. coli, Delftia sp. and Pseudomonas rhodesiae. Based on obtained results it can be concluded that biogenic AgNPs were capped with proteins and demonstrated potential as antimicrobial and anticancer agent.

Near-infrared emitting graphene quantum dots synthesized from reduced graphene oxide for in vitro/in vivo/ex vivo bioimaging applications

Near-infrared (NIR) emissive nanomaterials are desired for bioimaging and drug delivery applications due to the high tissue penetration depth of NIR light, enabling in vitro/ex vivo/in vivo fluorescence tracking. Considering the scarcity of NIR-fluorescing biocompatible nanostructures, we have for the first-time synthesized nanometer-sized reduced graphene oxide-derived graphene quantum dots (RGQDs) with NIR (950 nm) emission highly biocompatible in vitro with no preliminary toxic response in vivo. RGQDs are obtained in a high-yield (∼90%) top-down sodium hypochlorite/ultraviolet-driven synthetic process from non-emissive micron-sized reduced graphene oxide (RGO) flakes. This oxidation of RGO yields quantum dots with an average size of 3.54 ± 0.05 nm and a highly crystalline graphitic lattice structure with distinguishable lattice fringes. RGQDs exhibit excitation-independent emission in the visible and NIR-I region with a maximum NIR quantum yield of ∼7%. Unlike their parent material, RGQDs show substantial biocompatibility with ∼75%–80% cell viability up to high (1 mg ml−1) concentrations verified via both MTT and luminescence-based cytotoxicity assays. Tracked in vitro via their NIR fluorescence, RGQDs exhibit efficient internalization in HeLa cells maximized at 12 h with further anticipated excretion. In vivo, RGQDs introduced intravenously to NCr nude mice allow for fluorescence imaging in live sedated animals without the need in sacrificing those at imaging time points. Their distribution in spleen, kidneys, liver, and intestine assessed from NIR fluorescence in live mice, is further confirmed by excised organ analysis and microscopy of organ tissue slices. This outlines the potential of novel RGQDs as NIR imaging probes suitable for tracking therapeutic delivery in live animal models. A combination of smaller size, water-solubility, bright NIR emission, simple/scalable synthesis, and high biocompatibility gives RGQDs a critical advantage over a number of existing nanomaterials-based imaging platforms.

Nanosecond pulse laser-induced fabrication of gold and silver-integrated cinnamon shell structure: Tunable fluorescence dynamics and morphology

Various bio-compatible nanostructures with strong fluorescence and tailored physiochemical properties are desirable for the biomedicine and bioelectronics applications. Based on this fact, we prepared some gold/silver-integrated cinnamon shell structure (SS) using the nanosecond pulselaser ablation in liquid (PLAL) method and characterized systematically. The structure, morphology, color purity, absorption and fluorescence properties of these SS were tuned via the laser parameters variation to determine their practical applications feasibility. The HRTEM images of the produced SS showed the nucleation of the face centered cubic nanocrystallites with growth orientation along (111) and (200) lattice planes. The XRD and thermogravimetric analysis of the as-prepared samples confirmed their crystalline nature and thermal stability, respectively. The EDX spectra and maps of the studied SS revealed their corresponding atomic compositions and distributions. The FTIR and Raman spectra displayed the existence of bimolecular residues within the SS.These plasmonic SS demonstrated very strong UV–Vis absorbance, high fluorescence quantum yield (0.055) and blue emission color purity (CCT and CIE coordinate of 2454.93 K and 0.164, 0.1033) at room temperature. The lifetime decay analyses showed significant decrease of the donor in the presence of the luminescent SS (6.5 ± 5.46 ns), attributing to the interplay of radiative energy transfer andsubsequent emission of the photons at longer wavelengthin theSS. It is established that the PLAL fabricated SS may be useful for the antimicrobial drugs formulation and biophotonic applications.

Anticoronavirus Activity of Water-Soluble Pristine C60 Fullerenes: In Vitro and In Silico Screenings.

The emergence of a new member of the Coronaviridae family, which caused the 2020 pandemic, requires detailed research on the evolution of coronaviruses, their structure and properties, and interaction with cells. Modern nanobiotechnologies can address the many clinical challenges posed by the COVID-19 pandemic. In particular, they offer new therapeutic approaches using biocompatible nanostructures with "specific" antiviral activity. Therefore, the nanosized spherical-like molecule (0.72 nm in diameter) composed of 60 carbon atoms, C60 fullerene, is of interest in terms of fighting coronaviruses due to its high biological activity. In here, we aim to evaluate the effectiveness of anticoronavirus action of water-soluble pristine C60 fullerene in the model and in vitro systems. As a model, apathogenic for human coronavirus, we used transmissible gastroenteritis virus of swine (TGEV), which we adapted to the BHK-21 cell culture (kidney cells of a newborn Syrian hamster). The shape and size of the particles present in C60 fullerene aqueous colloidal solution (C60FAS) of given concentration, as well as C60FAS stability (value of zeta potential) were studied using microscopic (STM, scanning tunneling microscopy, and AFM, atomic force microscopy) and spectroscopic (DLS, dynamic light scattering) methods. The cytopathic effect of TGEV was determined with the help of a Leica DM 750 microscope and the degree of monolayer changes in cells was assessed. The microscopy of the viral suspension was performed using a high resolution transmission electron microscope (HRTEM; JEM-1230, Japan). Finally, the search for and design of optimal possible complexes between C60 fullerene and target proteins in the structure of SARS-CoV-2 coronavirus, evaluation of their stability in the simulated cellular environment were performed using molecular dynamics and docking methods. It was found that the maximum allowable cytotoxic concentration of C60 fullerene is 37.5±3.0μg/ml. The investigated C60FAS reduces the titer of coronavirus infectious activity by the value of 2.00±0.08TCID50/ml. It was shown that C60 fullerene interacts directly with SARS-CoV-2 proteins, such as RdRp (RNA-dependent RNA polymerase) and 3CLpro (3-chymotrypsin-like protease), which is critical for the life cycle of the coronavirus and, thus, inhibits its functional activity. In both cases, C60 fullerene fills the binding pocket and gets stuck there through stacking and steric interactions. Pioneer in vitro study to identify the anticoronavirus activity of water-soluble pristine C60 fullerenes indicates that they are highly promising for further preclinical studies, since a significant inhibition of the infectious activity of swine coronavirus of transmissible gastroenteritis in BHK-21 cell culture was found. According to molecular modeling results, it was shown that C60 fullerene can create the stable complexes with 3CLpro and RdRp proteins of SARS-CoV-2 coronavirus and, thus, suppress its functional activity.

Graphene oxide/alginate/silk fibroin composite as a novel bionanostructure with improved blood compatibility, less toxicity and enhanced mechanical properties

For biomedical applications, the design and synthesis of biocompatible nanostructures, are considered as critical challenges. In this study, graphene oxide (GO) was covalently modified by natural sodium alginate (Alg) polymer. By adding silk fibroin (SF) to this nanostructure, a hybrid nanobiocomposite (GO/Alg/SF) was resulted and its unique features were determined using FT-IR, EDX, FE-SEM, XRD and TG analyses. Because of using less toxic and high biocompatible materials, specific biological results were achieved. The cell viability of this novel nanostructure was 89.2 % and its hemolytic effect was less than 6% while the highest concentration (1000 μg/mL) of this nanostructure was chosen for these purposes. Also, high mechanical properties including the compressive strength (0.87 ± 0.034 (MPa)) and the compressive modulus (2.25 ± 0.091 (MPa)) were exposed. This nanostructure can be considered as a scaffold for wound dressing applications due to the mentioned properties.

Cu-In-S/ZnS@carboxymethylcellulose supramolecular structures: Fluorescent nanoarchitectures for targeted-theranostics of cancer cells

Although the field of oncology nanomedicine has shown indisputable progress in recent years, cancer remains one of the most lethal diseases, where the early diagnosis plays a pivotal role in the patient's prognosis and therapy. Herein, we report for the first time, the synthesis of biocompatible nanostructures composed of Cu-In-S and Cu-In-S/ZnS nanoparticles functionalized with carboxymethylcellulose biopolymer produced by a green aqueous process. These inorganic-organic colloidal nanohybrids developed supramolecular architectures stabilized by chemical functional groups of the polysaccharide shell with the fluorescent semiconductor nanocrystal core, which were extensively characterized by several morphological and spectroscopical techniques. Moreover, these nanoconjugates were covalently bonded with folic acid via amide bonds and electrostatically conjugated with the anticancer drug, producing functionalized supramolecular nanostructures. They demonstrated nanotheranostics properties for bioimaging and drug delivery vectorization effective for killing breast cancer cells in vitro. These hybrids offer a new nanoplatform using fluorescent polysaccharide-drug conjugates for cancer theranostics applications.

Formation of nanostructures on magnesium alloy by anodization for potential biomedical applications

In the present work, we have investigated the formation of nanostructures on AZ31 magnesium alloy using electrochemical anodization technique. The formed nanostructures were efficiently showed bone-like apatite formation followed by its gradual increase, when immersed in simulated body fluid (SBF) and it exhibited controlled degradation in 7 days. Cell viability study was performed using MG-63 cells (human osteosarcoma cell lines) and revealed that the nanostructured surface has excellent biocompatibility by enhancing both cell adhesion and cell growth. The detailed characterization of this anodized surface was evaluated by field emission scanning electron microscopy (FESEM) and energy-dispersive X-ray spectroscopy (EDS). Furthermore, surface-corrosion before and after anodization was examined by electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization studies in SBF. The in-depth studies bring out the fact that native oxide in the sample is converted to a biocompatible nanostructure, which is created due to anodization in a particular electrolyte solution containing ethylene glycol and hybrid hydrofluoric acid mixture.

Biocompatible nano-ripples structured surfaces induced by femtosecond laser to rebel bacterial colonization and biofilm formation

Structured surfaces with both anti-bacterial capability and biocompatibility are essential to medical devices including orthopedic implants. Over the past few years, numerous studies indicated that nanostructures such as nanotubes, nanowires, nano-pillars and nano-ripples were capable of repelling or killing bacteria, while the morphology and dimensions of the nanostructures showed essential influence on the adhesion and proliferation of cells. The long-term functionalities of implants depend on their reliable anti-bacterial performance at the same time enhanced biocompatibility. However, researches covering both these two aspects are still very limited. In this paper, we applied one-step femtosecond laser irradiation to produce three types of nano-ripples, and to investigate their anti-bacterial behavior and their biocompatibility. Our results demonstrate that all the three types of nano-ripples are capable of preventing bacterial colonization and biofilm formation, with their anti-bacteria rates towards E. coli respectively 43%, 49% and 56%. Meanwhile, the femtosecond laser induced nano-ripples exhibit good rat mesenchymal stem cells (MSCs) proliferation capacity and spreading performance, and the nano-ripples affect significantly the orientation of MSCs. The results offer valuable information and potentials on the anti-bacteria and biocompatibility of nanostructures.

The Fusion of Lipid and DNA Nanotechnology.

Lipid membranes form the boundary of many biological compartments, including organelles and cells. Consisting of two leaflets of amphipathic molecules, the bilayer membrane forms an impermeable barrier to ions and small molecules. Controlled transport of molecules across lipid membranes is a fundamental biological process that is facilitated by a diverse range of membrane proteins, including ion-channels and pores. However, biological membranes and their associated proteins are challenging to experimentally characterize. These challenges have motivated recent advances in nanotechnology towards building and manipulating synthetic lipid systems. Liposomes—aqueous droplets enclosed by a bilayer membrane—can be synthesised in vitro and used as a synthetic model for the cell membrane. In DNA nanotechnology, DNA is used as programmable building material for self-assembling biocompatible nanostructures. DNA nanostructures can be functionalised with hydrophobic chemical modifications, which bind to or bridge lipid membranes. Here, we review approaches that combine techniques from lipid and DNA nanotechnology to engineer the topography, permeability, and surface interactions of membranes, and to direct the fusion and formation of liposomes. These approaches have been used to study the properties of membrane proteins, to build biosensors, and as a pathway towards assembling synthetic multicellular systems.

Self‐Assembling Amyloid Sequences as Scaffolds for Material Design: A Case Study of Building Blocks Inspired From the Adenovirus Fiber Protein

In the last two decades the study of the properties of biological self‐organization has created a separate area of research, ranging from biomedicine and biotechnology to materials science and nanotechnology. In particular, the design of self‐assembling protein and peptide building blocks is often achieved by drawing inspiration from natural fibrous proteins such as collagen, elastin, silk, and spider silks that are built up from repetitive sequences. Self‐assembling proteins and peptides are water soluble and biocompatible nanostructures formed spontaneously under mild conditions through non‐covalent interactions. They form supramolecular structures such as ribbons, nanotubes, and fibers. The wide range of chemical functionalities found in peptides (i.e., 20 amino acids) enables the design and engineering of specific interactions with target materials for potential technological applications. Moreover, with the aid of computational methods, tailor made modifications can be inserted for the «on‐demand» design of functional amyloid materials binding to ions or compounds. Technologically, the self‐organized structures can be used as templates for the growth of inorganic materials, such as metallic nanoparticles (silver, gold, and platinum), silica, calcium phosphates etc. Self‐assembling peptides may also create hydrogels and entangled fibrous networks that can be used as scaffolds for attachment, growth and proliferation of living cells, allowing tissue repair and engineering. In this short review we summarize the progress made in the field with emphasis on our progress on how to translate fundamental structural knowledge from the adenovirus fiber protein into self‐assembling nanomaterials targeted for novel applications.

Low-Intensity Focused Ultrasound-Responsive Phase-Transitional Nanoparticles for Thrombolysis without Vascular Damage: A Synergistic Nonpharmaceutical Strategy.

Multimodal molecular imaging has shown promise as a complementary approach to thrombus detection. However, the simultaneous noninvasive detection and lysis of thrombi for cardiovascular diseases remain challenging. Herein, a perfluorohexane (PFH)-based biocompatible nanostructure was fabricated, namely, as-prepared Fe3O4-poly(lactic- co-glycolic acid)-PFH-CREKA nanoparticles (NPs), which combine phase transition (PT) thrombolysis capabilities with properties conducive to multimodal imaging. This well-developed PT agent responded effectively to low-intensity focused ultrasound (LIFU) by triggering the vaporization of liquid PFH to achieve thrombolysis. The presence of the CREKA peptide, which binds to the fibrin of the thrombus, allows targeted imaging and efficacious thrombolysis. Then, we found that, compared with thrombolysis using a non-phase-transition agent, PT thrombolysis can produce a robust decrease in the thrombus burden regardless of the acoustic power density of LIFU. In particular, the reduced energy for LIFU-responsive PT during the lysis process guarantees the superior safety of PT thrombolysis. After injecting the NPs intravenously, we demonstrated that this lysis process can be monitored with ultrasound and photoacoustic imaging in vivo to evaluate its efficacy. Therefore, this nonpharmaceutical strategy departs from routine methods and reveals the potential use of PT thrombolysis as an effective and noninvasive alternative to current thrombolytic therapy.

The Growing Development of DNA Nanostructures for Potential Healthcare-Related Applications.

DNA self‐assembly has proven to be a highly versatile tool for engineering complex and dynamic biocompatible nanostructures from the bottom up with a wide range of potential bioapplications currently being pursued. Primary among these is healthcare, with the goal of developing diagnostic, imaging, and drug delivery devices along with combinatorial theranostic devices. The path to understanding a role for DNA nanotechnology in biomedical sciences is being approached carefully and systematically, starting from analyzing the stability and immune‐stimulatory properties of DNA nanostructures in physiological conditions, to estimating their accessibility and application inside cellular and model animal systems. Much remains to be uncovered but the field continues to show promising results toward developing useful biomedical devices. This review discusses some aspects of DNA nanotechnology that makes it a favorable ingredient for creating nanoscale research and biomedical devices and looks at experiments undertaken to determine its stability in vivo. This is presented in conjugation with examples of state‐of‐the‐art developments in biomolecular sensing, imaging, and drug delivery. Finally, some of the major challenges that warrant the attention of the scientific community are highlighted, in order to advance the field into clinically relevant applications.

One-Pot Synthesis of PEG-Poly(amino acid) Block Copolymers Assembling Polymeric Micelles with PEG-Detachable Functionality.

Block copolymers composed of poly(ethylene glycol) (PEG) and poly(amino acids) (PAA) segments have shown exceptional features for developing biocompatible nanostructures. While the conventional methods for synthesizing PEG-PAA provide excellent control of the degree of polymerization and polydispersity, these protocols involve several steps, which increase the time and costs, and reduce the number of possible block copolymer designs. In this study, we developed a one-pot synthetic method for PEG-PAA block copolymers by doing sequential ring-opening polymerizations (ROP) of ethylene oxide (EO) and the N-carboxyanhydrides (NCAs) of amino acids promoted by the organic base 1,1,3,3-tetramethylguanidine (TMG) as the catalyst. The procedure was effectively used to synthesize PEG-poly(benzyl-l-glutamate) (PEG-PBLG) and PEG-poly(l-Lysine) (PEG-PLL) with narrow molecular weight distribution, comparable to that of block copolymers synthesized by the conventional method initiating the ROP of NCA by amine-terminated PEG. The resulting block copolymers present an ester bond between the PEG and the PAA segments, which can be gradually hydrolyzed in physiological conditions, being advantageous for improving the biocompatibility. Besides, we confirmed that the one-pot PEG-PBLG self-assembled into micelles in aqueous conditions, which showed comparable blood circulation and biodistribution to the micelles prepared from conventional PEG-PBLG. These results indicate the high potential of our one-pot synthetic approach for preparing hydrolyzable PEG-PAAs for constructing supramolecular assemblies.