Safety Assessment of 2D MXenes: In Vitro and In Vivo

MXenes, representing a new class of two-dimensional nanomaterial, have attracted intense interest in a variety of fields as supercapacitors, catalysts, and sensors, and in biomedicine. The assessment of the safety of MXenes and related materials in biological systems is thus an issue that requires significant attention. In this review, the toxic effects of MXenes and their derivatives are summarized through the discussion of current research into their behaviors in mammalian cells, animals and plants. Numerous studies have shown that MXenes have generally low cytotoxicity and good biocompatibility. However, a few studies have indicated that MXenes are toxic to stem cells and embryos. These in vitro and in vivo toxic effects are strongly associated with the dose of material, the cell type, the mode of exposure, and the specific type of MXene. In addition, surface modifications alter the toxic effects of MXenes. The stability of MXenes must be considered during toxicity evaluation, as degradation can lead to potentially toxic byproducts. Although research concerning the toxicity of MXenes is limited, this review provides an overview of the current understanding of interactions of MXenes with biological systems and suggests future research directions

Cytotoxicity Induction by the Oxidative Reactivity of Nanoparticles Revealed by a Combinatorial GNP Library with Diverse Redox Properties

It is crucial to establish relationship between nanoparticle structures (or properties) and nanotoxicity. Previous investigations have shown that a nanoparticle’s size, shape, surface and core materials all impact its toxicity. However, the relationship between the redox property of nanoparticles and their toxicity has not been established when all other nanoparticle properties are identical. Here, by synthesizing an 80-membered combinatorial gold nanoparticle (GNP) library with diverse redox properties, we systematically explored this causal relationship. The compelling results revealed that the oxidative reactivity of GNPs, rather than their other physicochemical properties, directly caused cytotoxicity via induction of cellular oxidative stress. Our results show that the redox diversity of nanoparticles is regulated by GNPs modified with redox reactive ligands

Fabrication of Gold Nanorods with Tunable Longitudinal Surface Plasmon Resonance Peaks by Reductive Dopamine

Hydroxyphenol compounds are often used as reductants in controlling the growth of nanoparticles. Herein, dopamine was used as an effective reductant in seed-mediated synthesis of gold nanorods (GNRs). The as-prepared GNRs (83 × 16 nm) were monodisperse and had a high degree of purity. The conversion ratio from gold ions to GNRs was around 80%. In addition, dopamine worked as an additive. At a very low concentration of hexadecyltrimethylammonium bromide (CTAB; 0.025 M), thinner and shorter GNRs (60 × 9 nm) were successfully prepared. By regulating the concentration of silver ions, CTAB, seeds, and reductant, GNRs with longitudinal surface plasmon resonance (LSPR) peaks ranging from 680 to 1030 nm were synthesized. The growth process was tracked using UV–vis–NIR spectroscopy, and it was found that a slow growth rate was beneficial to the formation of GNRs

Bio-Inspired Protein-Based Nanoformulations for Cancer Theranostics

Over the past decade, more interests have been aroused in engineering protein-based nanoformulations for cancer treatment. This excitement originates from the success of FDA approved Abraxane (Albumin-based paclitaxel nanoparticles) in 2005. The new generation of biocompatible endogenous protein-based nanoformulations is currently constructed through delivering cancer therapeutic and diagnostic agents simultaneously, as named potential theranostics. Protein nanoformulations are commonly incorporated with dyes, contrast agents, drug payloads or inorganic nanoclusters, serving as imaging-guided combinatorial cancer therapeutics. Employing the nature identity of proteins, the theranostics, escape the clearance by reticuloendothelial cells and have a long blood circulation time. The nanoscale sizet allows them to be penetrated deeply into tumor tissues. In addition, stimuli release and targeted molecules are incorporated to improve the delivery efficiency. The ongoing advancement of protein-based nanoformulations for cancer theranostics in recent 5 years is reviewed in this paper. Fine-designed nanoformulations based on albumin, ferritin, gelatin, and transferrin are highlighted from the literature. Finally, the current challenges are identified in translating protein-based nanoformulations from laboratory to clinical trials

Berberine reduces endothelial injury and arterial stiffness in spontaneously hypertensive rats

Background: Changes in circulating endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) are considered as a new perspective reflection of the endothelial injury and repair status. Our previous studies have demonstrated that berberine improved endothelial function and arterial stiffness in healthy subjects. In this study, we further investigated the effects of berberine on regulating the circulating EMPs and EPCs, and preventing endothelial dysfunction and arterial stiffness in spontaneously hypertensive rats (SHRs). Methods: Twenty male SHRs were randomly divided into two groups: Berberine-treated SHR group and vehicle-treated SHR group. The SHR rats were intragastrically treated with physiologic saline, berberine 50 mg/kg.d or vehicle for 4 weeks, respectively. Ten male Wistar-Kyoto (WKY) rats treated with vehicle served as normotensive controls. Tail systolic blood pressure was monitored every 2 weeks. At the end of the study, aortic pulse wave velocity (aPWV) was measured in vivo, and aorta were collected for measurement of endothelium-dependent vasodilation and immunohistological staining of elastic fiber. Peripheral blood was collected for circulating EMP detection and EPC culture. Results: Compared to normotensive rats, hypertensive rats displayed significantly higher circulating CD31+/CD42− MPs, lower number and colony-forming units (CFUs) of EPCs, worse endothelium-dependent vasodilation, and faster aPWV. Berberine treatment in SHRs partly reduced the blood pressure and circulating EMPs, and augmented EPC numbers and CFUs. In addition, berberine preserved arterial elasticity by lowering aPWV and increasing the content of arterial media elastin fiber, and improved endothelial function by maintaining better endothelium-dependent vasodilation. Robust relationship was observed among circulating CD31+/CD42− MPs, EPC numbers and aPWV. Conclusions: Abnormal changes of circulating EMPs and EPCs in SHRs are associated with endothelial dysfunction and arterial stiffness. Berberine may be a novel therapeutic option for the hypertension-related vascular injury in SHRs

Nanomaterial-Based Drug Delivery Systems for Pain Treatment and Relief: From the Delivery of a Single Drug to Co-Delivery of Multiple Therapeutics

The use of nanomaterials in drug delivery systems for pain treatment is becoming increasingly common. This review aims to summarize how nanomaterial-based drug delivery systems can be used to effectively treat and relieve pain, whether via the delivery of a single drug or a combination of multiple therapeutics. By utilizing nanoformulations, the solubility of analgesics can be increased. Meanwhile, controlled drug release and targeted delivery can be realized. These not only improve the pharmacokinetics and biodistribution of analgesics but also lead to improved pain relief effects with fewer side effects. Additionally, combination therapy is frequently applied to anesthesia and analgesia. The co-encapsulation of multiple therapeutics into a single nanoformulation for drug co-delivery has garnered significant interest. Numerous approaches using nanoformulation-based combination therapy have been developed and evaluated for pain management. These methods offer prolonged analgesic effects and reduced administration frequency by harnessing the synergy and co-action of multiple targets. However, it is important to note that these nanomaterial-based pain treatment methods are still in the exploratory stage and require further research to be effectively translated into clinical practice

Targeted Delivery of siRNA with pH-Responsive Hybrid Gold Nanostars for Cancer Treatment

In this work, we report the engineering of gold nanostars (GNS) to deliver small interfering RNA (siRNA) into HepG2 cells. The ligand DG-PEG-Lipoic acid (LA)-Lys-9R (hydrazone) was designed to functionalize GNS, and create the nanoparticles named as 9R/DG-GNS (hydrazone). In the ligand, 2-deoxyglucose (DG) is the targeting molecule, polyethylene glycol (PEG) helps to improve the dispersity and biocompatibility, 9-poly-d-arginine (9R) is employed to provide a positive surface charge and adsorb negative siRNA, and hydrazone bonds are pH-responsive and can avoid receptor-mediated endosomal recycling. Compared to GNS alone, 9R/DG-GNS (hydrazone) showed superior transfection efficiency. The expressions of cyclooxygenase-2 (COX-2) in HepG2 and SGC7901 cells were significantly suppressed by siRNA/9R/DG-GNS (hydrazone) complex. Notably, 9R/DG-GNS (hydrazone) possessed low cytotoxicity even at high concentrations in both normal cells and tumor cells. The combination treatment of siRNA/9R/DG-GNS (hydrazone) complex inhibited the cell growth rate by more than 75%. These results verified that the pH-responsive GNS complex is a promising siRNA delivery system for cancer therapy, and it is anticipated that near-infrared absorbing GNS with good photothermal conversion efficiency can be potentially used for photothermal therapy of tumors