Nanomedicine : nanotechnology, biology, and medicine最新文献

Gadolinium-based contrast agents (GBCAs) are used in around 40 % of MRI procedures. Despite initial perceptions of minimal risk, their long-term use has emphasized the need to reduce toxicity and develop more efficient GBCAs with extended blood retention. Advancements in nanomaterials have led to improved GBCAs, enhancing MRI diagnostics. This study synthesizes and characterizes nanostructured gadolinium(III) micelles as superior MRI contrast agents. The complexes, [Gd(L)2], where L is a ligand of the N-alkyl-N-methylglucamine surfactant series (L8, L10 or L12, L10), form nanostructured micelles in aqueous solution. Gd(L8)2 and Gd(L10)2 relaxivities remained stable across concentrations. Compared to Gd-DTPA, Gd(III) micelles showed enhanced T1-weighted MRI contrast. Gd(L12)2 micelles exhibited cytotoxicity against B16F10 melanoma cells (IC₅₀ 42.5 ± 2.2 μM) and L292L929 fibroblasts (IC₅₀ 52.0 ± 2.5 μM), with a selectivity index of 1.2. In vivo application in mice brain T2-weighted images suggests nanostructured Gd(III) micelles are promising MRI contrast agents for targeting healthy organs or tumors.

To address the adverse side effects associated with systemic high-dose methylprednisolone (MP) therapy for acute spinal cord injury (SCI), we have developed a N-2-hydroxypropyl methacrylamide copolymer-based MP prodrug nanomedicine (Nano-MP). Intravenous Nano-MP selectively targeted to the inflamed SCI lesion and significantly improved neuroprotection and functional recovery after acute SCI. In the present study, we comprehensively assessed the potential adverse side effects associated with the treatment in the SCI rat models, including reduced body weight and food intake, impaired glucose metabolism, and reduced musculoskeletal mass and integrity. In contrast to free MP treatment, intravenous Nano-MP after acute SCI not only offered superior neuroprotection and functional recovery but also significantly mitigated or even eliminated the aforementioned adverse side effects. The superior safety features of Nano-MP observed in this study further confirmed the clinical translational potential of Nano-MP as a highly promising drug candidate for better clinical management of patients with acute SCI.

Nucleic acid biomarker detection has great importance in the diagnosis of disease, the monitoring of disease progression and the classification of patients according to treatment decision making. Nucleic acid biomarkers found in the blood of patients have generated a lot of interest due to the possibility of being detected non-invasively which makes them ideal for monitoring and screening tests and particularly amenable to point-of-care (POC) or self-testing. A major challenge to POC molecular diagnostics is the need to enrich the target to optimise detection. In this work, we describe a microfabricated device for the enrichment of short dsDNA target sequences, which is especially valuable for potential detection methods, as it improves the probability of effectively detecting the target in downstream analyses. The device integrated a heating element and a temperature sensor with a microfluidic chamber to carry out the denaturation of the dsDNA combined with blocking-probes to enrich the target. This procedure was validated by fluorescence resonance energy transfer (FRET) technique, labelling DNA with a fluorophore and a quencher. As proof of concept, a 23-mer long dsDNA sequence corresponding to the L858R mutation of the EGFR gene was used. The qualitative results obtained determined that the most optimal blocking rate was obtained with the incorporation of 11/12-mer blocking-probes at a total concentration of 6 μM. This device is a powerful DNA preparation tool, which is an indispensable initial step for subsequent detection of sequences via nucleic acid hybridisation methods.

Nanophotothermolysis (NPhT) effect is considered to be an approach for the development of highly selective modalities for anticancer treatment. Herein, we evaluated an antitumor efficacy of NPhT with intravenously injected zinc phthalocyanine particles (ZnPcPs) in murine subcutaneous syngeneic tumor models. In S37 sarcoma-bearing mice a biodistribution of ZnPcPs was studied and the high antitumor efficacy of ZnPcPs-mediated NPhT was shown, including a response of metastatic lesions. The morphological investigation showed the main role of a local NPhT-induced vascular damage in the tumor growth and tumor spread inhibition. Murine tumors of different histological origin were not equally sensitive to the treatment. The results demonstrate a potential of ZnPcPs-mediated NPhT for treatment of surface tumors.

In equine medicine, assisted bone regeneration, including use of biomaterial substitutes like hydroxyapatite (HAP), is crucial for addressing bone defects. To follow-up on the outcome of HAP-based bone defect treatment, the advancement in quantified diagnostic imaging protocols is needed. This study aimed to quantify and compare the radiological properties of the HAP graft and natural equine bone using Magnetic Resonance (MR) and Computed Tomography (CT), both Single (SECT) and Dual Energy (DECT). SECT and DECT, allow for the differentiation of three HAP grain sizes, by progressive increase in relative density (RD). SECT, DECT, and MR enable the differentiation between natural cortical bone and synthetic HAP graft by augmentation in Effective Z and material density (MD) in HAP/Water, Calcium/Water, and Water/Calcium reconstructions, alongside the reduction in T2 relaxation time. The proposed quantification provided valuable radiological insights into the composition of HAP grafts, which may be useful in follow-up bone defect treatment.

Many strategies for regenerating the damaged tissues or degenerating cells are employed in regenerative medicine. Stem cell technology is a modern strategy of the recent approaches, particularly the use of mesenchymal stem cells (MCSs). The ability of MSCs to differentiate as well as their characteristic behaviour as paracrine effector has established them as key elements in tissue repair (Shaer et al., 2014¹). Recently, extracellular vesicles (EVs) shed by MSCs have emerged as a promising cell free therapy (Citation}Rani, S., Ryan, A. E., Griffin, M. D., and Ritter, T., 2015²). This comprehensive review encompasses MSCs-derived exosomes and their therapeutic potential as nanotherapeutics. We also discuss their potency as drug delivery nano-carriers in comparison with liposomes. A better knowledge of EVs behaviour in vivo and of their mechanism of action are key to determine parameters of an optimal formulation in pilot studies and to establish industrial processes.

The use of mesenchymal stromal cells (MSCs) for treating chronic inflammatory disorders, wounds, and ischemia-reperfusion injuries has shown improved healing efficacy. However, the poor survival rate of transplanted cells due to oxidative stress in injured or inflamed tissue remains a significant concern for MSC-based therapies. In this study, we developed a new approach to protect MSCs from oxidative stress, thereby improving their survival in a wound microenvironment and enhancing their therapeutic effect. We produced PLGA nanoparticles loaded with the cytoprotective phytochemical silibinin (SBN), and used them to modify MSCs. Upon internalization, these nanoformulations released SBN, activating the Nrf2/ARE signaling pathway, resulting in threefold reduction in intracellular ROS content and improved cell survival under oxidative stress conditions. Modification of MSCs with SBN-loaded PLGA nanoparticles increased their survival upon transplantation to full-thickness cutaneous wounds and improved wound healing. This study suggests that MSC modification with cytoprotective nanoparticles could be a promising approach for improving wound healing.

Remote magneto-mechanical actuation (MMA) of magnetic nanoparticles (MNP) is emerging as a promising therapy method in oncology. However, translation to the clinic faces the challenge of whole-body action and the reluctance about indiscriminate mechanical action of the nanoparticles on tumor and healthy cells. Here, we show how the MMA method based on magnetically-rotated gold-coated MNP boosts only the activity of an unbound antitumor drug, without physical damage of cells via MNP. Therefore, in clinical practice, the effect of antitumor drug can be safely increased systemically while maintaining drug concentrations at current doses.

The primary challenge in percutaneous coronary interventions for vascular restenosis is the occurrence of restenosis, which is defined by the excessive proliferation of neointimal tissue. Herein, our research team suggests that exosomes obtained from PSC, when paired with quercetin (Q@PSC-E), successfully reduce neointimal hyperplasia in a Sprague-Dawley rat model. Furthermore, the physical properties of the synthesized Q@PSC-E were examined using UV–vis, DLS, and FT-IR characterization techniques. The rats were subjected to balloon injury (BI) utilizing a 2-Fr Fogarty arterial embolectomy balloon catheter. Intimal hyperplasia and the degree of VSMC proliferation were evaluated using histological analysis in the rat groups that received a dosage of Q@PSC-E at 30 mg/kg/d. Significantly, Q@PSC-E inhibited cell proliferation through a pathway that does not include lipoxygenase, as demonstrated by [³H] thymidine incorporation, MTT, and flow cytometry studies. Additionally, the data indicate that Q@PSC-E hinders cell proliferation by targeting particular events that promote cell growth, including the activation of Akt and NF-κB, disruption of cell-cycle progression and also obstructs the ERK signaling pathway.

Surgical site infection (SSI) significantly affects patient recovery time, health outcomes and quality of life which is closely associated with the use of implants or mesh. Sutures are the most frequently used implants that play a significant role in the development of SSI. Studies have demonstrated that the administration of effective bactericidal and anti-inflammatory treatments can significantly decrease the incidence of SSI. To address this concern, a versatile suture was engineered by coating MoO_3-X nanodots in this study. The incorporation of MoO_3-X nanodots endowed the suture with desirable antibacterial and anti-inflammatory properties that were evaluated in in vitro and in vivo experiments. The results showed its remarkable ability to facilitate wound healing and prevent SSI through its dual action of combating bacterial infection and reducing inflammation. These findings highlight the promising potential of this multifunctional surgical suture as a versatile tool to promote better outcomes in surgical procedures.