International Journal of Nanomedicine

Our medical research library holds 12 studies published in International Journal of Nanomedicine (2008–2024). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 12 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: DOVE Medical Press
• Published: 2006 to the present, New Zealand
• Language: English
• ISSN: 1176-9114 (print), 1178-2013 (electronic)
• Its record in the NLM Catalog

2020s

• Specific Targeting of Mesothelin-Expressing Malignant Cells Using Nanobody-Functionalized Magneto-Fluorescent Nanoassemblies. T. Briolay, J. Fresquet, D. Meyer, et al. 2024;19:633-650. PubMed · Publisher · Free full text

  Abstract

  Introduction: Most current anti-cancer therapies are associated with major side effects due to a lack of tumor specificity. Appropriate vectorization of drugs using engineered nanovectors is known to increase local concentration of therapeutic molecules in tumors while minimizing their side effects. Mesothelin (MSLN) is a well-known tumor associated antigen overexpressed in many malignancies, in particular in malignant pleural mesothelioma (MPM), and various MSLN-targeting anticancer therapies are currently evaluated in preclinical and clinical assays. In this study, we described, for the first time, the functionalization of fluorescent organic nanoassemblies (NA) with a nanobody (Nb) targeting MSLN for the specific targeting of MSLN expressing MPM cancer cells.

  Methods: Cell lines from different cancer origin expressing or not MSLN were used. An Nb directed against MSLN was coupled to fluorescent NA using click chemistry. A panel of endocytosis inhibitors was used to study targeted NA internalization by cells. Cancer cells were grown in 2D or 3D and under a flow to evaluate the specificity of the targeted NA. Binding and internalization of the targeted NA were studied using flow cytometry, confocal microscopy and transmission electron microscopy.

  Results: We show that the targeted NA specifically bind to MSLN-expressing tumor cells. Moreover, such functionalized NA appear to be internalized more rapidly and in significantly larger proportions compared to naked ones in MSLN+ MPM cells, thereby demonstrating both the functionality and interest of the active targeting strategy. We demonstrated that targeted NA are mainly internalized through a clathrin-independent/dynamin-dependent endocytosis pathway and are directed to lysosomes for degradation. A 3D cell culture model based on MSLN-expressing multicellular tumor spheroids reveals NA penetration in the first superficial layers.

  Conclusion: Altogether, these results open the path to novel anticancer strategies based on MSLN-activated internalization of NA incorporating drugs to promote specific accumulation of active treatments in tumors.

  © 2024 Briolay et al.

• The 3D-Printed Ordered Bredigite Scaffold Promotes Pro-Healing of Critical-Sized Bone Defects by Regulating Macrophage Polarization. Y. Xuan, L. Li, C. Zhang, et al. 2023;18:917-932. PubMed · Publisher · Free full text

  Abstract

  Background: Repairing critical-sized bone defects secondary to traumatic or tumorous damage is a complex conundrum in clinical practice; in this case, artificial scaffolds exhibited preferable outcomes. Bredigite (BRT, Ca7MgSi4O16) bioceramic possesses excellent physicochemical properties and biological activity as a promising candidate for bone tissue engineering.

  Methods: Structurally ordered BRT (BRT-O) scaffolds were fabricated by a three-dimensional (3D) printing technique, and the random BRT (BRT-R) scaffolds and clinically available β-tricalcium phosphate (β-TCP) scaffolds were compared as control groups. Their physicochemical properties were characterized, and RAW 264.7 cells, bone marrow mesenchymal stem cells (BMSCs), and rat cranial critical-sized bone defect models were utilized for evaluating macrophage polarization and bone regeneration.

  Results: The BRT-O scaffolds exhibited regular morphology and homogeneous porosity. In addition, the BRT-O scaffolds released higher concentrations of ionic products based on coordinated biodegradability than the β-TCP scaffolds. In vitro, the BRT-O scaffolds facilitated RWA264.7 cells polarization to pro-healing M2 macrophage phenotype, whereas the BRT-R and β-TCP scaffolds stimulated more pro-inflammatory M1-type macrophages. A conditioned medium derived from macrophages seeding on the BRT-O scaffolds notably promoted the osteogenic lineage differentiation of BMSCs in vitro. The cell migration ability of BMSCs was significantly enhanced under the BRT-O-induced immune microenvironment. Moreover, in rat cranial critical-sized bone defect models, the BRT-O scaffolds group promoted new bone formation with a higher proportion of M2-type macrophage infiltration and expression of osteogenesis-related markers. Therefore, in vivo, BRT-O scaffolds play immunomodulatory roles in promoting critical-sized bone defects by enhancing the polarization of M2 macrophages.

  Conclusion: 3D-printed BRT-O scaffolds can be a promising option for bone tissue engineering, at least partly through macrophage polarization and osteoimmunomodulation.

  © 2023 Xuan et al.

2010s

• Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study. E. Cova, L. Pandolfi, M. Colombo, et al. 2019;14:773-785. PubMed · Publisher · Free full text

  Abstract

  Purpose: Malignant pleural mesothelioma (MPM) is an aggressive tumor characterized by poor prognosis. Its incidence is steadily increasing due to widespread asbestos exposure. There is still no effective therapy for MPM. Pemetrexed (Pe) is one of the few chemotherapeutic agents approved for advanced-stage disease, although the objective response to the drug is limited. The use of gold nanoparticles (GNPs) as a drug delivery system promises several advantages, including specific targeting of malignant cells, with increased intracellular drug accumulation and reduced systemic toxicity, and, in the case of MPM, direct treatment administration into the pleural space. This study aims at exploring CD146 as a potential MPM cell-specific target for engineered Pe-loaded GNPs and to assess their effectiveness in inhibiting MPM cell line growth.

  Methods: MPM cell lines and primary cultures obtained by pleural effusions from MPM patients were assayed for CD146 expression by flow cytometry. Internalization by MPM cell lines of fluorescent dye-marked GNPs decorated with a monoclonal anti CD146 coated GNPs (GNP-HC) was proven by confocal microscopy. The effects of anti CD146 coated GNPs loaded with Pe (GNP-HCPe) on MPM cell lines were evaluated by cell cycle (flow cytometry), viability (MTT test), clonogenic capacity (soft agar assay), ROS production (electric paramagnetic resonance), motility (wound healing assay), and apoptosis (flow cytometry).

  Results: GNP-HC were selectively uptaken by MPM cells within 1 hour. MPM cell lines were blocked in the S cell cycle phase in the presence of GNP-HCPe. Both cell viability and motility were significantly affected by nanoparticle treatment compared to Pe. Apoptotic rate and ROS production were significantly higher in the presence of nanoparticles. Clonogenic capacity was completely inhibited following nanoparticle internalization.

  Conclusion: GNP-HCPe treatment displays in vitro antineoplastic action and is more effective than Pe alone in inhibiting MPM cell line malignant phenotype. The innovative use of specifically targeted GNPs opens the perspective of local intrapleural administration to avoid normal cell toxicity and enhance chemotherapy efficacy.

• Prolonged retention of liposomes in the pleural cavity of normal mice and high tumor distribution in mice with malignant pleural effusion, after intrapleural injection. A. Marazioti, K. Papadia, A. Giannou, et al. 2019;14:3773-3784. PubMed · Publisher · Free full text

  Abstract

  Background: Intrapleural administration of compounds is a lung targeted, innovative therapeutic strategy for mesothelioma, which can be refined as a route for drug delivery that minimizes the potential for systemic toxicity. However, little is currently known about the retention of liposomal drugs at the site, after such topical administration. Purpose: To evaluate the retention of liposomes in lungs following intrapleural injection, and how this might be modulated by liposome properties and disease progression. Methods: DiR-incorporating liposomes with various lipid compositions and sizes were prepared, characterized (for size distribution and zeta potential) and injected intrapleurally in normal mice and mice with malignant pleural effusion (MPE). DiR retention in pleural cavity was followed by biofluorescence imaging. Results: Experimental results demonstrate that liposome size and PEG-coating, have a significant effect on residence time in the pleural cavity; negative surface charge does not. More than 20% liposomal-DiR is retained 24 d post-injection (in some cases), indicating the high potential towards localized diseases. Ex-vivo liposomal-DiR signal in tumors of MPE mice was similar to signal in liver, suggesting high tumor targeting potential of intrapleurally injected liposomes. Finally, no difference was noticed in liposomal-DiR retention between tumor-inoculated (MPE) and healthy mice, indicating the stability of liposomes in the presence of effusion (in MPE mice). Conclusion: The current study provides novel insights for using liposomes by intrapleural administration for the treatment of lung diseases.

• Stromelysin-2 (MMP-10) facilitates clearance and moderates inflammation and cell death following lung exposure to long multiwalled carbon nanotubes. T.C. Vandivort, T.P. Birkland, T.P. Domiciano, et al. 2017;12:1019-1031. PubMed · Publisher · Free full text

  Abstract

  Multiwalled carbon nanotubes (MWCNTs) are nanomaterials composed of multiple layers of graphene cylinders with unique properties that make them valuable for a number of industries. However, rising global production has led to concerns regarding potential occupational exposures to them as raw materials during handling. This is especially true for long MWCNT fibers, whose aspect ratio has been posited to initiate pathology similar to that of asbestos. Matrix metalloproteinases (MMPs) are a class of extracellular endopeptidases that control various processes related to tissue repair, inflammation, and more. Stromelysin-2 (MMP-10) has roles in modulating macrophage activation and function, and hence, we used an MMP-10 null (Mmp10-/-) mouse model to assess its role in controlling lung responses to inhaled long MWCNTs. Oropharyngeal aspiration of long MWCNTs (80 µg/mouse) by wild-type mice induced expression of Mmp10 mRNA, which was accompanied by a robust inflammatory response characterized by elevated expression of Tnfa, Il6, and Il1b. In Mmp10-/- mice, we found that absence of MMP-10 led to impaired pulmonary clearance of MWCNTs and reduced macrophage cell survival. Exposure of wild-type bone marrow-derived macrophages (BMDMs) and alveolar macrophages to MWCNTs caused a rapid, dose-dependent upregulation of Mmp10 mRNA expression, which was accompanied by expression of pro-inflammatory products (Il6 and Il1b). These products were further enhanced in Mmp10-/- macrophages, resulting in increased caspase-3-dependent cell death compared with wild-type cells. These findings indicate that MMP-10 facilitates the clearance of MWCNTs and moderates the pro-inflammatory response of exposed alveolar and infiltrated macrophages.

• Biodegradable mesoporous calcium-magnesium silicate-polybutylene succinate scaffolds for osseous tissue engineering. X. Zhang, C. Zhang, W. Xu, et al. 2015;10:6699-708. PubMed · Publisher · Free full text

  Abstract

  The structural features of bone engineering scaffolds are expected to exhibit osteoinductive behavior and promote cell adhesion, proliferation, and differentiation. In the present study, we employed synthesized ordered mesoporous calcium-magnesium silicate (om-CMS) and polybutylene succinate (PBSu) to develop a novel scaffold with potential applications in osseous tissue engineering. The characteristics, in vitro bioactivity of om-CMS/PBSu scaffold, as well as the cellular responses of MC3T3-E1 cells to the composite were investigated. Our results showed that the om-CMS/PBSu scaffold possesses a large surface area and highly ordered channel pores, resulting in improved degradation and biocompatibility compared to the PBSu scaffold. Moreover, the om-CMS/PBSu scaffold exhibited significantly higher bioactivity and induced apatite formation on its surface after immersion in the simulated body fluid. In addition, the om-CMS/PBSu scaffold provided a high surface area for cell attachment and released Ca, Mg, and Si ions to stimulate osteoblast proliferation. The unique surface characteristics and higher biological efficacy of the om-CMS/PBSu scaffold suggest that it has great potential for being developed into a system that can be employed in osseous tissue engineering.

• Biological responses according to the shape and size of carbon nanotubes in BEAS-2B and MESO-1 cells. H. Haniu, N. Saito, Y. Matsuda, et al. 2014;9:1979-90. PubMed · Publisher · Free full text

  Abstract

  This study aimed to investigate the influence of the shape and size of multi-walled carbon nanotubes (MWCNTs) and cup-stacked carbon nanotubes (CSCNTs) on biological responses in vitro. Three types of MWCNTs - VGCF(®)-X, VGCF(®)-S, and VGCF(®) (vapor grown carbon fibers; with diameters of 15, 80, and 150 nm, respectively) - and three CSCNTs of different lengths (CS-L, 20-80 μm; CS-S, 0.5-20 μm; and CS-M, of intermediate length) were tested. Human bronchial epithelial (BEAS-2B) and malignant pleural mesothelioma cells were exposed to the CNTs (1-50 μg/mL), and cell viability, permeability, uptake, total reactive oxygen species/superoxide production, and intracellular acidity were measured. CSCNTs were less toxic than MWCNTs in both cell types over a 24-hour exposure period. The cytotoxicity of endocytosed MWCNTs varied according to cell type/size, while that of CSCNTs depended on tube length irrespective of cell type. CNT diameter and length influenced cell aggregation and injury extent. Intracellular acidity increased independently of lysosomal activity along with the number of vacuoles in BEAS-2B cells exposed for 24 hours to either CNT (concentration, 10 μg/mL). However, total reactive oxygen species/superoxide generation did not contribute to cytotoxicity. The results demonstrate that CSCNTs could be suitable for biological applications and that CNT shape and size can have differential effects depending on cell type, which can be exploited in the development of highly specialized, biocompatible CNTs.

• "One-stop shop" spectral imaging for rapid on-site diagnosis of lung cancer: a future concept in nano-oncology. K. Darwiche, P. Zarogoulidis, L. Krauss, et al. 2013;8:4533-42. PubMed · Publisher · Free full text

  Abstract

  Background: There are currently many techniques and devices available for the diagnosis of lung cancer. However, rapid on-site diagnosis is essential for early-stage lung cancer, and in the current work we investigated a new diagnostic illumination nanotechnology.

  Methods: Tissue samples were obtained from lymph nodes, cancerous tissue, and abnormal intrapulmonary lesions at our interventional pulmonary suites. The following diagnostic techniques were used to obtain the samples: endobronchial ultrasound bronchoscopy; flexible bronchoscopy; and rigid bronchoscopy. Flexible and rigid forceps were used because several of the patients were intubated using a rigid bronchoscope. In total, 30 tissue specimens from 30 patients were prepared. CytoViva® illumination nanotechnology was subsequently applied to each of the biopsy tissue slides.

  Results: A spectral library was created for adenocarcinoma, epidermal growth factor receptor mutation-positive adenocarcinoma, squamous cell carcinoma, usual interstitial pneumonitis, non-specific interstitial pneumonitis, typical carcinoid tumor, sarcoidosis, idiopathic pulmonary fibrosis, small cell neuroendocrine carcinoma, thymoma, epithelioid and sarcomatoid mesothelioma, cryptogenic organizing pneumonia, malt cell lymphoma, and Wegener's granulomatosis.

  Conclusion: The CytoViva software, once it had created a specific spectral library for each entity, was able to identify the same disease again in subsequent paired sets of slides of the same disease. Further evaluation of this technique could make this illumination nanotechnology an efficient rapid on-site diagnostic tool.

• Targeted delivery of let-7a microRNA encapsulated ephrin-A1 conjugated liposomal nanoparticles inhibit tumor growth in lung cancer. H.Y. Lee, K.A. Mohammed, F. Kaye, et al. 2013;8:4481-94. PubMed · Publisher · Free full text

  Abstract

  MicroRNAs (miRs) are small noncoding RNA sequences that negatively regulate the expression of target genes by posttranscriptional repression. miRs are dysregulated in various diseases, including cancer. let-7a miR, an antioncogenic miR, is downregulated in lung cancers. Our earlier studies demonstrated that let-7a miR inhibits tumor growth in malignant pleural mesothelioma (MPM) and could be a potential therapeutic against lung cancer. EphA2 (ephrin type-A receptor 2) tyrosine kinase is overexpressed in most cancer cells, including MPM and non-small-cell lung cancer (NSCLC) cells. Ephrin-A1, a specific ligand of the EphA2 receptor, inhibits cell proliferation and migration. In this study, to enhance the delivery of miR, the miRs were encapsulated in the DOTAP (N-[1-(2.3-dioleoyloxy)propyl]-N,N,N-trimethyl ammonium)/Cholesterol/DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[cyanur(polyethylene glycol)-2000])-PEG (polyethylene glycol)-cyanur liposomal nanoparticles (LNP) and ephrin-A1 was conjugated on the surface of LNP to target receptor EphA2 on lung cancer cells. The LNP with an average diameter of 100 nm showed high stability, low cytotoxicity, and high loading efficiency of precursor let-7a miR and ephrin-A1. The ephrin-A1 conjugated LNP (ephrin-A1-LNP) and let-7a miR encapsulated LNP (miR-LNP) showed improved transfection efficiency against MPM and NSCLC. The effectiveness of targeted delivery of let-7a miR encapsulated ephrin-A1 conjugated LNP (miR-ephrin-A1-LNP) was determined on MPM and NSCLC tumor growth in vitro. miR-ephrin-A1-LNP significantly increased the delivery of let-7a miR in lung cancer cells when compared with free let-7a miR. In addition, the expression of target gene Ras was significantly repressed following miR-ephrin-A1-LNP treatment. Furthermore, the miR-ephrin-A1-LNP complex significantly inhibited MPM and NSCLC proliferation, migration, and tumor growth. Our results demonstrate that the engineered miR-ephrin-A1-LNP complex is an effective carrier for the targeted delivery of small RNA molecules to lung cancer cells. This could be a potential therapeutic approach against tumors overexpressing the EphA2 receptor.

• Effect of dispersants of multi-walled carbon nanotubes on cellular uptake and biological responses. H. Haniu, N. Saito, Y. Matsuda, et al. 2011;6:3295-307. PubMed · Publisher · Free full text

  Abstract

  Although there have been many reports about the cytotoxicity of multi-walled carbon nanotubes (MWCNTs), the results are still controversial. To investigate one possible reason, the authors investigated the influence of MWCNT dispersants on cellular uptake and cytotoxicity. Cytotoxicity was examined (measured by alamarBlue(®) assay), as well as intracellular MWCNT concentration and cytokine secretion (measured by flow cytometry) in human bronchial epithelial cells (BEAS-2B) exposed to a type of highly purified MWCNT vapor grown carbon fiber (VGCF(®), Shōwa Denkō Kabushiki-gaisha, Tokyo, Japan) in three different dispersants (gelatin, carboxylmethyl cellulose, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine). The authors also researched the relationship between the intracellular concentration of MWCNTs and cytotoxicity by using two cell lines, BEAS-2B and MESO-1 human malignant pleural mesothelioma cells. The intracellular concentration of VGCF was different for each of the three dispersants, and the levels of cytotoxicity and inflammatory response were correlated with the intracellular concentration of VGCF. A relationship between the intracellular concentration of VGCF and cytotoxic effects was observed in both cell lines. The results indicate that dispersants affect VGCF uptake into cells and that cytotoxicity depends on the intracellular concentration of VGCF, not on the exposed dosage. Thus, toxicity appears to depend on exposure time, even at low VGCF concentrations, because VGCF is biopersistent.

• Elucidation mechanism of different biological responses to multi-walled carbon nanotubes using four cell lines. H. Haniu, N. Saito, Y. Matsuda, et al. 2011;6:3487-97. PubMed · Publisher · Free full text

  Abstract

  We examined differences in cellular responses to multi-walled carbon nanotubes (MWCNTs) using malignant pleural mesothelioma cells (MESO-1), bronchial epithelial cells (BEAS-2B), neuroblastoma cells (IMR-32), and monoblastic cells (THP-1), before and after differentiation. MESO-1, BEAS-2B and differentiated THP-1 cells actively endocytosed MWCNTs, resulting in cytotoxicity with lysosomal injury. However, cytotoxicity did not occur in IMR-32 or undifferentiated THP-1 cells. Both differentiated and undifferentiated THP-1 cells exhibited an inflammatory response. Carbon blacks were endocytosed by the same cell types without lysosomal damage and caused cytokine secretion, but they did not cause cytotoxicity. These results indicate that the cytotoxicity of MWCNTs requires not only cellular uptake but also lysosomal injury. Furthermore, it seems that membrane permeability or cytokine secretion without cytotoxicity results from several active mechanisms. Clarification of the cellular recognition mechanism for MWCNTs is important for developing safer MWCNTs.

2000s

• Cytotoxicity and reactive oxygen species generation from aggregated carbon and carbonaceous nanoparticulate materials. K.M. Garza, K.F. Soto, L.E. Murr. 2008;3(1):83-94. PubMed · Free full text

  Abstract

  We have investigated the cytotoxicity and reactive oxygen species (ROS) generation for indoor and outdoor soots: candle, wood, diesel, tire, and natural gas burner soots--along with surrogate black carbon, various multiwall carbon nanotube aggregate materials, TiO2 (anatase) and chrysotile asbestos as reference materials. All soots were observed utilizing TEM and FESEM to be composed of aggregated, primary spherules (20-80 nm diameter) forming complex, branched fractal structures. These spherules were composed of intercalated, turbostratic arrangements of curved graphene fragments with varying concentrations ofpolycyclic aromatic hydrocarbon (PAH) isomers. In vitro cultures with an immortalized human lung epithelial carcinoma cell line (A549) treated with these materials showed decreased cell viability and variations in ROS production, with no correlations to PAH content. The data demonstrate that soots are cytotoxic and that cytotoxicity is not related to PAH content but is related to ROS generation, suggesting that soot induces cellular oxidative stress and that cell viability assays can be indicators of ROS production.

Browse every journal in the library or the library by type of article, or return to medical research.