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As customizable biomaterials, hydrogels have attracted great promise in several industries, including drug delivery, tissue engineering, biosensing and regenerative medicine. Three-dimensional networks of these hydrophilic polymers exhibit special properties, such as increased water content, soft and flexible texture and biocompatibility, making them excellent candidates to simulate the extracellular matrix and promote cell development and tissue regeneration. In this review paper, we provide a comprehensive overview of hydrogels, focusing on the design concepts, synthesis processes and characterization techniques. Different types of hydrogel materials, including natural polymers, synthetic polymers and hybrid hydrogels, along with their unique properties and applications are discussed. Improvements in hydrogel-based platforms for controlled drug delivery are being investigated. Recent advances in bioprinting processes using hydrogels to create complex tissue constructs with excellent spatial control are also explored. Hydrogel performance is examined across multiple variables, including mechanical properties, degradation behavior and biological interactions, with an emphasis on the importance of tailoring hydrogel qualities for specific applications. This review paper also provides insights into future directions in hydrogel research, including stimuli-sensitive hydrogels, self-healing hydrogels and bioactive hydrogels, which promise promising advances in the field. In general, the aim of this review paper is to provide the reader with a detailed understanding of hydrogels and all of their potential applications, making them a valuable tool for scientists and researchers working on biomaterials and tissue engineering.
Branched metal nanoparticles present a promising new class of materials, which have great potential as sensors, catalysts, drug carriers, and imaging agents, owing to their unique nanostructures, physicochemical properties, optical properties, and other characteristics. Many efforts have recently been devoted to the wet-chemical synthesis of branched metal nanoparticles. Seed-mediated growth and seedless growth are two main routes for producing branched metal nanoparticles. Most particle synthesis methods can be modified for different metal systems. In this review, various synthesis methods for the fabrication of branched monometallic, bimetallic, and multimetallic nanoparticles and also branched polymer core-metal nanoshell composite nanoparticles are summarized, catagorized, and discussed. The relevance and performance of such nanostructured materials with regard to their optical properties which arise from localized surface plasmon resonances are summarized, and their potential as excellent substrates for surface enhanced Raman scattering (SERS) is reviewed. Other applications of branched nanoparticles such as drug delivery vehicle, medical imaging agent, catalysis, and magnetism are briefly introduced.
In drug delivery, the nanoparticles must be of proper size and charge to achieve high efficacy and low toxicity of associated therapeutics. In this study, nanoparticles were developed via ionic gelation of two polysaccharide-based molecules, negatively charged polysialic acid (PSA) and positively charged N,N,N-trimethylchitosan (TMC). PSA is unique in that the highly hydrated backbone may be used in a manner similar to that of poly(ethylene glycol) to extend circulation times. Although not necessary for nanoparticle formation, sodium tripolyphosphate (TPP) was added to enhance stability, as indicated by a reduced polydispersity. We investigated three different ratios by weight of PSA:TMC (0.5:1, 1:1, 1:2 and five different TPP concentrations ranging from 0.1 mg/ml to 0.8 mg/ml. As controls, nanoparticles were also formed without PSA from chitosan and TMC with TPP. Optimal size and surface charge were achieved with a PSA:TMC weight ratio of 0.5:1 and a TPP concentration 0.2 mg/ml. For the nanoparticles prepared in the latter fashion, a more in depth characterization was conducted. The nanoparticles were distinct solid, spherical nanogels with a size of 106 ± 25 nm, an ideal size to reduce uptake by the reticuloendothelial system while facilitating passive targeting of diseased tissue. The zeta potential of the nanoparticles was +33.9 ± 1.2 mV, suggesting that the nanoparticles will be stable under physiological conditions. Encapsulation and controlled release by the nanoparticles was demonstrated using methotrexate, a therapeutic indicated in both cancer and rheumatoid arthritis. The results obtained thus far strongly indicate that PSA–TMC nanoparticles are suitable drug carrier systems for systemic administration.
Current chemotherapy treatments are limited by poor drug solubility, rapid drug clearance and systemic side effects. Additionally, drug penetration into solid tumors is limited by physical diffusion barriers [e.g., extracellular matrix (ECM)]. Nanoparticle (NP) blood circulation half-life, biodistribution and ability to cross extracellular and cellular barriers will be dictated by NP composition, size, shape and surface functionality. Here, we investigated the effect of surface charge of poly(lactide)-poly(ethylene glycol) NPs on mediating cellular interaction. Polymeric NPs of equal sizes were used that had two different surface functionalities: negatively charged carboxyl (COOH) and neutral charged methoxy (OCH3). Cellular uptake studies showed significantly higher uptake in human brain cancer cells compared to noncancerous human brain cells, and negatively charged COOH NPs were uptaken more than neutral OCH3 NPs in 2D culture. NPs were also able to load and control the release of paclitaxel (PTX) over 19 days. Toxicity studies in U-87 glioblastoma cells showed that PTX-loaded NPs were effective drug delivery vehicles. Effect of surface charge on NP interaction with the ECM was investigated using collagen in a 3D cellular uptake model, as collagen content varies with the type of cancer and the stage of the disease compared to normal tissues. Results demonstrated that NPs can effectively diffuse across an ECM barrier and into cells, but NP mobility is dictated by surface charge. In vivo biodistribution of OCH3 NPs in intracranial tumor xenografts showed that NPs more easily accumulated in tumors with less collagen. These results indicate that a robust understanding of NP interaction with various tumor environments can lead to more effective patient-tailored therapies.
Exosomes were discovered more than 30 years ago. Only recently has their importance been recognized for intercellular communication. Exosomes, with their size ranging from 30 nm to 100 nm, are lipid bilayer nanoparticles and secreted by many different types of cells with versatile functions. Exosomes contain macromolecules and exist in various body fluids, including blood, urine, milk and ascites fluid. Due to their specific property, exosomes are very promising in the fields of disease diagnosis and therapy. Nanotechnology is a great tool that will be helpful in basic research and the application of exosomes. Here, we briefly review the function and potential use of exosomes in nanomedicine.
The plasmodium of slime mould Physarum polycephalum has recently received significant attention for its value as a highly malleable amorphous computing substrate. In laboratory-based experiments, nanoscale artificial circuit components were introduced into the P. polycephalum plasmdodium to investigate the electrical properties and computational abilities of hybridized slime mould. It was found through a combination of imaging techniques and electrophysiological measurements that P. polycephalum is able to internalize a range of electrically active nanoparticles (NPs), assemble them in vivo and distribute them around the plasmodium. Hybridized plasmodium is able to form biomorphic mineralized networks inside the living plasmodium and the empty trails left following its migration, both of which facilitate the transmission of electricity. Hybridization also alters the bioelectrical activity of the plasmodium and likely influences its information processing capabilities. It was concluded that hybridized slime mould is a suitable substrate for producing functional unconventional computing devices.
Induced pluripotent stem cells (iPSCs) have a tremendous potential in biomedical applications. Nanotechnology has played an essential role on reprogramming iPSCs. In the current review, we will summarize recent progress on application of nanoparticles and other nanotechnology-based platforms in iPSC generation and in study of iPSC biology. We will also highlight the importance of nanotechnology on biomedical application of iPSCs.
Cancer threatens the life and well-being of human beings. Millions of newly diagnosed cancer cases and a large number of deaths caused by cancer are reported each year in the world. Early detection and effective treatment are key to reduce cancer mortality, which can be potentially realized by using “theranostics”. Theranostics are a group of hybrid nanoparticles that perform in cancer patients to provide both diagnostic and therapeutic functions through a single nano-sized structure. In particular, core-shell structured theranostics have shown unique physicochemical properties, allowing them to facilitate molecular/cell targeting, bio-imaging, and drug delivery functions. This review, therefore, aims to present and discuss the recent development of research on core-shell structured theranostics. Specifically, it focuses on core-shell structured theranostics made of metals, silica and polymers. Different aspects, such as synthesis and structure, of core-shell structured theranostics are discussed in this review. This review helps readers to have a good understanding of the design and fabrication of core-shell structured theranostics.
Because of the exceptional qualities, nano-hydroxyapatites, or n-HA, are excellent materials for diverse applications. It is simple and convenient to synthesize from various natural ingredients. The synthesis of n-HA from eggshells, a typical domestic waste product in the neighborhood, was the primary goal of this study project. This synthesis of n-HA was performed using ammonia and orthophosphoric acid as chemical reagents. The synthesized n-HA have been characterized by UV (Ultraviolet), FTIR (Fourier Transformed Infrared Spectroscopy), SEM (Scanning Electron Microscopy), TEM (Transmission Electron Microscopy), and XRD (X-ray diffraction) analysis. The peak formed by the UV analysis verified the successful formation of n-HA in the solution. The bandgap has been determined through additional research on the UV data. The SEM and TEM images show the size and form of the synthesized n-HA. Based on TEM observations, the synthesized n-HA has a size in the range of 10 to 40 nm. The peak ensures the n-HA’s crystallinity that the XRD analysis produced. The obtained crystallinity was 74%.
This study outlines a drug delivery mechanism that utilizes two independent vehicles, allowing for delivery of chemically and physically distinct agents. The mechanism was utilized to deliver a new anti-cancer combination therapy consisting of piperlongumine (PL) and TRAIL to treat PC3 prostate cancer and HCT116 colon cancer cells. PL, a small-molecule hydrophobic drug, was encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles. TRAIL was chemically conjugated to the surface of liposomes. PL was first administered to sensitize cancer cells to the effects of TRAIL. PC3 and HCT116 cells had lower survival rates in vitro after receiving the dual nanoparticle therapy compared to each agent individually. In vivo testing involved a subcutaneous mouse xenograft model using NOD-SCID gamma mice and HCT116 cells. Two treatment cycles were administered over 48 hours. Higher apoptotic rates were observed for HCT116 tumor cells that received the dual nanoparticle therapy compared to individual stages of the nanoparticle therapy alone.
This article discusses the role of the protein corona in delivery systems with tagged nanoparticles and how knowledge of the protein corona can help in optimizing delivery. The basic question is whether and how the binding of proteins and other biomolecules at the nanoparticle surface interfere with the interaction between a tag and its receptor. This is an interesting problem in many respects, but most intriguing are the observed differences in delivery efficiency in vivo compared with protein-free in vitro conditions. In order to understand possible situations that the nanoparticle will face in a protein-rich biological environment, we will first describe the formation of a protein corona and thereafter discuss potential perturbations of the delivery systems when moving from in vitro testing to in vivo applications. We emphasize the role of mathematical modeling in optimizing the design of functionalized nanoparticles to achieve high success of delivery.
Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD, http://www.ncbi.nlm.nih.gov/books/NBK5330/), more than 6000 molecular imaging agents with sufficient preclinical evaluation have been reported to date in the literature and this number increases by 250–300 novel agents each year. The majority of these agents are radionuclides, which are developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Contrast agents for magnetic resonance imaging (MRI) account for only a small part. This is largely due to the fact that MRI is currently not a fully quantitative imaging technique and is less sensitive than PET and SPECT. However, because of the superior ability to simultaneously extract molecular and anatomic information, molecular MRI is attracting significant interest and various targeted nanoparticle contrast agents have been synthesized for MRI. The first and one of the most critical steps in developing a targeted nanoparticle contrast agent is target selection, which plays the central role and forms the basis for success of molecular imaging. This chapter discusses the design principles of targeted contrast agents in the emerging frontiers of molecular MRI.
Nanotechnology and the exploitation of nanoparticles for clinical use have been considerably gaining grounds in medicine and varied fields of biological sciences. The advantages of using nanoparticles like sitespecific drug delivery, stability in vitro and in vivo as well as reduced side-effects compared to conventional drugs have made it the nextgeneration therapy for the treatment of diseases. However, toxicological studies have revealed that the uptake of novel nanomaterials may pose serious threats to health by ways of immune responses. Engineered nanoparticles from gold, carbon, metal oxides and polymers have been shown to affect the immune cells and organs in a number of ways. Herein, we have enumerated the potential implications of uptake and localization of certain widely used nanoparticles and their interaction with the immunological barrier inside living organisms. We have introduced a brief account of the various toxicological assessment tests currently being used by various research organization for ensuring the safety and efficacy of nanoparticles before being approved for human administration and consumption. Lastly, we have also tried to highlight some immerging new concepts of conjugating nanomaterials with biological molecules which, besides reducing inflammatory responses, increases the specificity of target thus improving the effect of nano-based drugs.