Prospective Preliminary <i>In Vitro</i> Investigation of a Magnetic Iron Oxide Nanoparticle Conjugated with Ligand CD80 and VEGF Antibody As a Targeted Drug Delivery System for the Induction of Cell Death in Rodent Osteosarcoma Cells

Kovach, AnneMarie Kay; Gambino, Jen M; Nguyen, Vina; Nelson, Zach; Szasz, Taylor P.; Liao, Jun; Williams, Lakiesha N.; Bulla, Sandra C; Prabhu, Raj

doi:10.1089/biores.2016.0020

Cited by 13 publications

(9 citation statements)

References 24 publications

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“…This suggested that the imbalance expression profile of cytokines and chemokines might contribute to the homeostatsis disturbances in systemic environments and disease progression of osteosarcoma. Due to the well‐understood function and being the potential therapeutic target of VEGF for osteosarcoma , we chose CXCL8 as the targeting chemokine for further analyses to improve the understanding of immunopathogenesis of osteosarcoma. CXCL8, which is also known as IL‐8, is a chemokine produced by various cell types, and mainly plays a proinflammatory role by recruitment and activation of neutrophils/granulocytes to the site of infection or tissue injury .…”

Section: Discussionmentioning

confidence: 99%

CXCL8 promotes the invasion of human osteosarcoma cells by regulation of PI3K/Akt signaling pathway

Jiang

Wang

Miao

et al. 2017

APMIS

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Chemokine cysteine-X-cysteine motif ligand 8 (CXCL8) is up-regulated in many malignancies, indicating that CXCL8 takes part in tumor progression. However, the expression and function of CXCL8 in osteosarcoma remained not fully elucidated. In this study, expressions of 12 cytokines and chemokines were measured in the serum from 12 of normal controls (NCs) and 25 of osteosarcoma patients. The human osteosarcoma cell line MG-63 was stimulated by recombinant CXCL8 to further analyze invasion, proliferation, apoptosis, cell cycles, cytokine secretions, and signaling pathways. We found that serum concentrations of CXCL8 and vascular endothelial growth factor were elevated in osteosarcoma patients in comparison with those in NCs. CXCL8 stimulation led to enhancement of invasion and suppression of late stage apoptosis in MG-63 cells. Moreover, secretions of MMPs by MG-63 cells were also increased upon stimulation. However, early stage apoptosis, proliferation, and cell cycles were not affected by CXCL8 treatment. Furthermore, CXCL8 stimulation induced elevations of phosphorylated PI3K and Akt, but not PKC or FAK. In conclusion, our findings suggested that CXCL8 enhanced the invasion and suppressed late stage apoptosis of osteosarcoma cells probably via influencing PI3K/Akt signaling pathway and elevating the expression of MMPs. CXCL8 may promote disease progression of osteosarcoma as a protumorigenic molecule, and may be served as a new therapeutic target for osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

CXCL8 promotes the invasion of human osteosarcoma cells by regulation of PI3K/Akt signaling pathway

Jiang

Wang

Miao

et al. 2017

APMIS

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“…However, the drawback of most existing HCC-targeted MRI molecular probes is that the singularity of the target may weaken the detection specificity and sensitivity, considering the tumor heterogeneity and false positive or false negative diagnoses associated with cancer biomarkers. Therefore, a more complex targeted probe design such as double antigen-targeted probes are well appreciated to precisely capture the molecular features of tumors[22,23] and, hence, are expected to further enhance the precision and imaging quality of small HCC or MHCC lesions.…”

Section: Introductionmentioning

confidence: 99%

Development and in vitro study of a bi-specific magnetic resonance imaging molecular probe for hepatocellular carcinoma

Ma¹,

Wang²,

Liu³

et al. 2019

WJG

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BACKGROUND Hepatocellular carcinoma (HCC) ranks second in terms of cancer mortality worldwide. Molecular magnetic resonance imaging (MRI) targeting HCC biomarkers such as alpha-fetoprotein (AFP) or glypican-3 (GPC3) offers new strategies to enhance specificity and help early diagnosis of HCC. However, the existing iron oxide nanoparticle-based MR molecular probes singly target AFP or GPC3, which may hinder their efficiency to detect heterogeneous micro malignant HCC tumors < 1 cm (MHCC). We hypothesized that the strategy of double antibody-conjugated iron oxide nanoparticles which simultaneously target AFP and GPC3 antigens may potentially be used to overcome the tumor heterogeneity and enhance the detection rate for MRI-based MHCC diagnosis. AIM To synthesize an AFP/GPC3 double antibody-labeled iron oxide MRI molecular probe and to assess its impact on MRI specificity and sensitivity at the cellular level. METHODS A double antigen-targeted MRI probe for MHCC anti-AFP–USPIO–anti-GPC3 (UAG) was developed by simultaneously conjugating AFP andGPC3 antibodies to a 5 nm ultra-small superparamagnetic iron oxide nanoparticle (USPIO). At the same time, the singly labeled probes of anti-AFP–USPIO (UA) and anti-GPC3–USPIO (UG) and non-targeted USPIO (U) were also prepared for comparison. The physical characterization including morphology (transmission electron microscopy), hydrodynamic size, and zeta potential (dynamic light scattering) was conducted for each of the probes. The antigen targeting and MRI ability for these four kinds of USPIO probes were studied in the GPC3-expressing murine hepatoma cell line Hepa1-6/GPC3. First, AFP and GPC3 antigen expression in Hepa1-6/GPC3 cells was confirmed by flow cytometry and immunocytochemistry. Then, the cellular uptake of USPIO probes was investigated by Prussian blue staining assay and in vitro MRI (T2-weighted and T2-map) with a 3.0 Tesla clinical MR scanner. RESULTS Our data showed that the double antibody-conjugated probe UAG had the best specificity in targeting Hepa1-6/GPC3 cells expressing AFP and GPC3 antigens compared with single antibody-conjugated and unconjugated USPIO probes. The iron Prussian blue staining and quantitative T2-map MRI analysis showed that, compared with UA, UG, and U, the uptake of double antigen-targeted UAG probe demonstrated a 23.3% ( vs UA), 15.4% ( vs UG), and 57.3% ( vs U) increased Prussian stained cell percentage and a 14.93% ( vs UA), 9.38% ( vs UG), and 15.3% ( vs U) reduction of T2 relaxation time, respectively. Such bi-specific probe might have the potential to overcome tumor heterogeneity. Meanwhile, the coupling of two antibodies did not influence the magnetic performance of USPIO, and the relatively small hydrodynamic size (59.60 ± 1.87 nm) of do...

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“…Endothelial growth factor (VEGF) antibody was chosen as the targeted agent for the elevated production of VEGF antigen in OS cells (43), which plays a significant role in tumor angiogenesis processes. For the treatment of OS, an iron oxide nanoparticle complex conjugated to VEGF antibody and the ligand cluster of differentiation 80 (CD80) was developed (44). This combination approach would be able to target not just the extensively expressed VEGF antigen in OS cells, but also the increased expression of the surface cell receptor cytotoxic T lymphocyteassociated antigen-4 (CTLA4) (44).…”

Section: Antibodies As Targeting Ligandsmentioning

confidence: 99%

“…For the treatment of OS, an iron oxide nanoparticle complex conjugated to VEGF antibody and the ligand cluster of differentiation 80 (CD80) was developed (44). This combination approach would be able to target not just the extensively expressed VEGF antigen in OS cells, but also the increased expression of the surface cell receptor cytotoxic T lymphocyteassociated antigen-4 (CTLA4) (44).…”

Section: Antibodies As Targeting Ligandsmentioning

confidence: 99%

Targeted Delivery of Chemotherapeutic Agents for Osteosarcoma Treatment

Xie

Wang

et al. 2022

Front. Oncol.

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Since osteosarcoma (OS) is an aggressive bone cancer with unknown molecular pathways of etiology and pathophysiology, improving patient survival has long been a challenge. The conventional therapy is a complex multidisciplinary management that include radiotherapy, chemotherapy which followed by surgery and then post-operative adjuvant chemotherapy. However, they have severe side effects because the majority of the medicines used have just a minor selectivity for malignant tissue. As a result, treating tumor cells specifically without damaging healthy tissue is currently a primary goal in OS therapy. The coupling of chemotherapeutic drugs with targeting ligands is a unique therapy method for OS that, by active targeting, can overcome the aforementioned hurdles. This review focuses on advances in ligands and chemotherapeutic agents employed in targeted delivery to improve the capacity of active targeting and provide some insight into future therapeutic research for OS.

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Prospective Preliminary In Vitro Investigation of a Magnetic Iron Oxide Nanoparticle Conjugated with Ligand CD80 and VEGF Antibody As a Targeted Drug Delivery System for the Induction of Cell Death in Rodent Osteosarcoma Cells

Cited by 13 publications

References 24 publications

CXCL8 promotes the invasion of human osteosarcoma cells by regulation of PI3K/Akt signaling pathway

CXCL8 promotes the invasion of human osteosarcoma cells by regulation of PI3K/Akt signaling pathway

Development and in vitro study of a bi-specific magnetic resonance imaging molecular probe for hepatocellular carcinoma

Targeted Delivery of Chemotherapeutic Agents for Osteosarcoma Treatment

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