A ternary-complex of a suicide gene, a RAGE-binding peptide, and polyethylenimine as a gene delivery system with anti-tumor and anti-angiogenic dual effects in glioblastoma

Choi, Eun‐Ji; Oh, Jungju; Lee, Dahee; Lee, Jaewon; Tan, Xiaonan; Kim, Minkyung; Kim, Gyeungyun; Piao, Chunxian; Lee, Minhyung

doi:10.1016/j.jconrel.2018.04.021

Cited by 21 publications

(10 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In glioblastomas, RAGE is expressed on tumor cells, endothelial cells, stromal cells, and tumorassociated macrophages comprising microglia and myeloid-derived macrophages (112). RAGE binding activates downstream signaling pathways that stimulate cell proliferation, survival, and migration via increased angiogenesis, in ammation, and reduced apoptosis, While blocking RAGE signaling suppresses tumor growth and metastasis (113)(114)(115)(116). Despite the inhibition of oncogenic mechanisms at the cellular level, we found the macrophage activation and immune response as activated biological processes in treated gliospheres.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Anti-Oncogenic Activities Exhibited By Secretomes Of Mesenchymal Stem Cells Are Mediated By Modulation Of KITLG and DKK1 Genes In Glioma Stem Cells.

Aslam

Abusharieh

Abuarqoub

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background. Cancer stem cells (CSCs) use their stemness properties such as self renewal, toxicity, plasticity, and communication with the tumor microenvironment (TME) to perpetuate their lineage and survive chemotherapy. Learning how to interrupt the self renewal ability or modulate the interaction of CSCs with the TME signaling will dramatically improve therapeutic impact on patient’s remission. Anti-tumor properties of mesenchymal stem cells (MSCs) are currently under investigations and different approaches have been applied to gain beneficial effects However, different types of MSCs yielded different conflicting results. In order to investigate if different types of MSCs preconditioned in the same culture conditions can exert alike anti oncogenic effect on glioma stem cells, we planned this study. Methods. GSCs were isolated from U87 cell line by FACS cell sorter, characterized and established as gliospheres. Condition media from MSCs of Wharton Jelly (WJ-MSCs) and bone marrow (BM-MSCs) were harvested and used as treatments on glioshperes (3D) to investigate the effect on proliferation, invasion and self renewal properties of GSCs. Microarray analysis was used to determine the effect at molecular level. Specific human CSC gene arrays were applied to validate the findings of the microarray explicitly the pluripotency of the GSCs. Results. Our results from functional and molecular assays showed that condition media (CM) from both types of MSCs inhibited the metabolism by interrupting oxidative phosphorylation, arrested the cell cycle, induced cell differentiation, targeted the pluripotency and up-regulated the immune response in GSCs. Moreover , condition media from both types of MSCs significantly affected the same genes (KITLG and DKK1) causing a similar effect while using slightly different routes and signaling pathways signifying their individual effects.Conclusion.We conclude that mesenchymal stem cells possess antitumor properties and paracrine factors of mesenchymal stem cells in combination with anti-immune modalities can provide novel therapeutic targets for glioma treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Anti-Oncogenic Activities Exhibited By Secretomes Of Mesenchymal Stem Cells Are Mediated By Modulation Of KITLG and DKK1 Genes In Glioma Stem Cells.

Aslam

Abusharieh

Abuarqoub

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The results obtained suggested that HSV‐TK nanoparticles showed remarkable anti‐glioma effects and survival benefits in an invasive mouse orthotopic brain tumor model by inhibiting cellular proliferation and inducing apoptosis. Even some inspiring events occurred in cells and animals in vitro , indicating that clinical experiments with respect to brain tumor suicide gene therapy have been extremely successful. Hence, more effort is required aiming to explore new approaches that make use of the HSV‐TK/GCV system in brain tumor treatment.…”

Section: Therapeutic Genes For Cns Diseasesmentioning

confidence: 99%

Non‐viral nucleic acid delivery to the central nervous system and brain tumors

Wang

Huang

2019

The Journal of Gene Medicine

View full text Add to dashboard Cite

Gene therapy is a rapidly emerging remedial route for many serious incurable diseases, such as central nervous system (CNS) diseases. Currently, nucleic acid medicines, including DNAs encoding therapeutic or destructive proteins, small interfering RNAs or microRNAs, have been successfully delivered to the CNS with gene delivery vectors using various routes of administration and have subsequently exhibited remarkable therapeutic efficiency. Among these vectors, non‐viral vectors are favorable for delivering genes into the CNS as a result of their many special characteristics, such as low toxicity and pre‐existing immunogenicity, high gene loading efficiency and easy surface modification. In this review, we highlight the main types of therapeutic genes that have been applied in the therapy of CNS diseases and then outline non‐viral gene delivery vectors.

show abstract

“…Dendritic poly-L -lysine (DPLL) was first developed to condense TNF-α siRNA (siTNF-α) and form the positively charged DPLL/ siTNF-α (DsT) NCs. RAGE-binding peptide (RBP), a cationic antagonist to the receptor for advanced glycation end products (RAGE) that can block the interaction between RAGE and its ligands and down-regulate pro-inflammatory factors, [43][44][45] was reversibly modified with cis-aconitic anhydride (CA) to afford the negatively charged pro-peptide, RBP-cis-aconitic amide (RC), which was utilized to coat the DsT NCs. The obtained RC/DPLL/siTNF-α (RCDsT) NCs possessed negative surface charges, thereby allowing efficient mucus penetration upon intratracheal administration.…”

Section: Introductionmentioning

confidence: 99%

“…[47,48] In the meantime, the reactivated RBP bound to RAGE on inflamed macrophage membranes and thereafter down-regulated the various pro-inflammatory cytokines such as TNF-α, interleukin-1β (IL-1β), interleukin-6 (IL-6), etc. [43][44][45] Such an inflammation-sheddable pro-peptide not only provides an effective approach to solve the dilemma between mucus penetration and cellular uptake but also cooperates with siTNF-α to alleviate the cytokine storm toward ALI treatment (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Pro‐Peptide‐Reinforced, Mucus‐Penetrating Pulmonary siRNA Delivery Mitigates Cytokine Storm in Pneumonia

Yang

Duan

et al. 2021

Adv Funct Materials

Self Cite

View full text Add to dashboard Cite

Pulmonary delivery of anti-inflammatory siRNA holds great potential in mitigating the cytokine storm during severe pneumonia. However, commonly utilized polycationic siRNA delivery vehicles can hardly penetrate the mucus barrier, thus greatly hurdling their therapeutic efficacy. Herein, TNF-α siRNA (siTNF-α) delivery nanocomplexes (NCs) are engineered with mucus/cytomembrane dual-penetration capabilities, realized via surfacecoating of NCs with RC, an inflammation-sheddable, charge-reversal pro-peptide of RAGE-binding peptide (RBP). RC-coated dendritic poly-Llysine/siTNF-α (DsT) NCs possess negative surface charges, and can thus efficiently penetrate the mucus layer after intratracheal administration. In the inflamed alveolar space with mild acidity, RC recovers to the cationic RBP and shed off, re-exposing the DsT NCs that efficiently transfect the alveolar macrophages and provokes TNF-α silencing. Thus, siTNF-α and RBP cooperatively alleviate the uncontrolled inflammation during acute lung injury. This study renders a unique approach for mediating trans-mucus nucleic acid delivery, and will find promising utilities for the treatment of severe pneumonia.

show abstract

A ternary-complex of a suicide gene, a RAGE-binding peptide, and polyethylenimine as a gene delivery system with anti-tumor and anti-angiogenic dual effects in glioblastoma

Cited by 21 publications

References 50 publications

WITHDRAWN: Anti-Oncogenic Activities Exhibited By Secretomes Of Mesenchymal Stem Cells Are Mediated By Modulation Of KITLG and DKK1 Genes In Glioma Stem Cells.

WITHDRAWN: Anti-Oncogenic Activities Exhibited By Secretomes Of Mesenchymal Stem Cells Are Mediated By Modulation Of KITLG and DKK1 Genes In Glioma Stem Cells.

Non‐viral nucleic acid delivery to the central nervous system and brain tumors

Pro‐Peptide‐Reinforced, Mucus‐Penetrating Pulmonary siRNA Delivery Mitigates Cytokine Storm in Pneumonia

Contact Info

Product

Resources

About