Nanomedicine: Nanotechnology, Biology and Medicine最新文献

Extracellular vesicles (EVs), nanovesicles released by cells to effectively exchange biological information, are gaining interest as drug delivery system. Yet, analogously to liposomes, they show short blood circulation times and accumulation in the liver and the spleen. For tissue specific delivery, EV surfaces will thus have to be functionalized. We present a novel platform for flexible modification of EVs with target-specific ligands based on the avidin-biotin system. Genetic engineering of donor cells with a glycosylphosphatidylinositol-anchored avidin (GPI-Av) construct allows the isolation of EVs displaying avidin on their surface, functionalized with any biotinylated ligand. For proof of concept, GPI-Av EVs were modified with i) a biotinylated antibody or ii) de novo designed and synthesized biotinylated ligands binding carbonic anhydrase IX (CAIX), a membrane associated enzyme overexpressed in cancer. Functionalized EVs showed specific binding and uptake by CAIX-expressing cells, demonstrating the power of the system to prepare EVs for cell-specific drug delivery.

Spinal cord injury (SCI) is a severe traumatic disease because of its complications and multi-organ dysfunction. After the injury, the disruption of microenvironment homeostasis in the lesion demolishes the surrounding healthy tissues via various pathways. The microenvironment regulation is beneficial for neural and functional recovery. Sustained release, cellular uptake, and long-term retention of therapeutic molecules at the impaired sites are important for continuous microenvironment improvement. In our study, a local-implantation system was constructed for SCI treatment by encapsulating exosomes derived from Flos Sophorae Immaturus (so-exos) in a polydopamine-modified hydrogel (pDA-Gel). So-exos are used as nanoscale natural vehicles of rutin, a flavonoid phytochemical that is effective in microenvironment improvement and nerve regeneration. Our study showed that the pDA-Gel-encapsulated so-exos allowed rapid improvement of the impaired motor function and alleviation of urination dysfunction by modulating the spinal inflammatory and oxidative conditions, thus illustrating a potential SCI treatment through a combinational delivery of so-exos.

In addition to exhibited antioxidant and anti-inflammatory activity, fullerene C60 is a promising wound healing agent. An important stage in the production of fullerene-based ointments is the stability of the aqueous fullerene dispersion (AFD) with minimum size of colloidal fullerene aggregates and sufficiently high concentration. To achieve these parameters tangential flow filtration of fullerene C60 was used (“green technology”).

As estimated by small-angle neutron scattering and dynamic light scattering purified AFDs with narrow-size distribution nanoclusters have a size of 6 nm and are assembled into agglomerates which reach a size of 150 nm.

The ability of the AFD to exhibit regenerative activity was studied using the animal wound model. This study shows for the first time that the fullerene-based composition stimulates the healing of wounds of various origins. We assume that the mechanism of the AFD wound-healing activity is associated with the aryl hydrocarbon receptor and macrophages activity.

Copper diethyldithiocarbamate [Cu(DDC)₂] is a promising anticancer agent. However, its poor water solubility is a significant obstacle to clinical application. In previous studies, we developed a stabilized metal ion ligand complex (SMILE) method to prepare Cu(DDC)₂ nanoparticle (NP) to address the drug delivery challenge. In the current study, we investigate the use of Cu(DDC)₂ NP for treating P-glycoprotein (P-gp) mediated drug-resistant cancers. We tested its anticancer efficacy with extensive in vitro cell-based assays and in vivo xenograft tumor model. We also explored the mechanism of overcoming drug resistance by Cu(DDC)₂ NP. Our results indicate that Cu(DDC)₂ NP is not a substrate of P-gp and thus can avoid P-gp mediated drug efflux. Further, the Cu(DDC)₂ NP does not inhibit the activity or the expression of P-gp.

Respiratory viruses usually induced similar clinical symptoms at early infection. Herein, we presented a multichannel surface-enhanced Raman scattering-based lateral flow immunoassay (SERS-based LFA) using high-performance magnetic SERS tags for the simultaneous ultrasensitive detection of respiratory viruses, namely influenza A virus (H1N1), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) in biological samples. As-prepared magnetic SERS tags can directly enrich and capture target viruses without pretreatment of samples, avoiding the interference of impurities in the samples as well as improving the sensitivity. With the capture-detection method, the detection limits of the proposed assay reached 85 copies mL⁻¹, 8 pg mL⁻¹, and 8 pg mL⁻¹ for H1N1, SARS-CoV-2 and RSV, respectively. Moreover, the detection properties of the proposed method for target viruses in throat swab samples were verified, suggesting its remarkable potential for the early and rapid differential diagnosis of respiratory viruses.

Tumor-derived exosomes are capable of inducing immune dysfunction and favoring the formation and progression of tumor. The major histocompatibility complex class I (MHC-I) plays a key role in antitumor immune responses by presenting tumor antigens to cytotoxic T lymphocytes. However, the role of tumor-derived circulating exosomal MHC-I on immune system activation remains unclear. We demonstrated that low level of glioma cells-derived exosomal MHC-I was associated with the dysfunction of CD8⁺ T cells in immune activation and cytotoxicity. MHC-I upregulation in exosomes restored antigen presentation of glioma cells and activated CD8⁺ T cells to exert robust antitumor immune response in combination with immune checkpoint blockade. Collectively, these data provided evidences for an important interplay between exosomal MHC-I and CD8⁺ T cells to activate systemic antitumor immune response, and interpreted how glioma cells evaded immunosurveillance, induced immunosuppression and were resistant to immunotherapy from the perspective of systemic immunity.

Polymer nanomedicines with anti-tumor activity should exhibit sufficient stability during systemic circulation to the target tissue; however, they should release the active drug selectively in the tumor. Thus, choice of a tumor-specific stimuli-sensitive spacer between the drug and the carrier is critical. Here, a series of polymer conjugates of anti-cancer drugs doxorubicin and pirarubicin covalently bound to copolymers based on N-(2-hydroxypropyl)methacrylamide via various enzymatically cleavable oligopeptide spacers were prepared and characterized. The highest rate of the drug release from the polymer carriers in presence of the lysosomal protease cathepsin B was determined for the copolymers with Val-Cit-Aba spacer. Copolymers containing pirarubicin were more cytotoxic and showed higher internalization rate than the corresponding doxorubicin counterparts. The conjugates containing GFLG and Val-Cit-Aba spacers exhibited the highest anti-tumor efficacy in vivo against murine sarcoma S-180, the highest rate of the enzymatically catalyzed drug release, and the highest cytotoxicity in vitro.

Meniere's disease (MD) is a progressive inner ear disorder involving recurrent and prolonged episodes or attacks of vertigo with associated symptoms, resulting in a significantly reduced quality of life for sufferers. In most cases, MD starts in one ear; however, in one-third of patients, the disorder progresses to the other ear. Unfortunately, the etiology of the disease is unknown, making the development of effective treatments difficult. Nanomaterials, including nanoparticles (NPs) and nanocarriers, offer an array of novel diagnostic and therapeutic applications related to MD. NPs have specific features such as biocompatibility, biochemical stability, targetability, and enhanced visualization using imaging tools. This paper provides a comprehensive and critical review of recent advancements in nanotechnology-based diagnostic and therapeutic approaches for MD. Furthermore, the crucial challenges adversely affecting the use of nanoparticles to treat middle ear disorders are investigated. Finally, this paper provides recommendations and future directions for improving the performances of nanomaterials on theragnostic applications of MD.

Personalized medicine approach in radiotherapy requires the delivery of precise dose to the tumor. The concept is to increase the effectiveness of radiotherapy while sparing the surrounding heathy tissue. This can be achieved by the use of high-Z metal-based nanoparticles (NPs) as radio-enhancers and PET imaging for mapping NPs distribution to guide the irradiation. In the present study, radio-enhancing platinum NPs were radiolabeled and imaged to assess their pharmacokinetics over time. PET imaging of these NPs revealed high enhanced permeation and retention effect. The maximal tumor accumulation (4.8 ± 0.8 %ID/cc) was observed at 24 h post-injection along with persistent accumulation of the NPs, especially at the tumor ring, even after several days. These properties positively suggest the potential clinical use of these NPs.