Systemic brain tumor delivery of synthetic protein nanoparticles for glioblastoma therapy

Gregory, Jeffrey A.; Kadiyala, Padma; Doherty, Robert; Cadena, Melissa; Habeel, Samer; Ruoslahti, Erkki; Löwenstein, Pedro R.; Castro, María G.; Lahann, Joerg

doi:10.1038/s41467-020-19225-7

Cited by 180 publications

(149 citation statements)

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“…iRGD ligand exhibits more effective penetration ability and higher accumulation in tumors compared to the most of cyclic RGD ligands [ 40 ]. The most recent study demonstrates the crossing of blood-brain-barrier and systemic siRNA delivery to glioblastoma by means of iRGD-modified protein nanoparticles based on polymerized human serum albumin [ 41 ].…”

Section: Introductionmentioning

confidence: 99%

Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma

et al. 2021

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Uterine leiomyoma (UL) is one of the most common benign tumors in women that often leads to many reproductive complications. Suicide genetherapy was suggested as a promising approach for UL treatment. In the present study, we describe iRGD ligand-conjugated cysteine-rich peptide carrier RGD1-R6 for targeted DNA delivery to αvβ3 integrin-expressing primary UL cells. The physico-chemical properties, cytotoxicity, transfection efficiency and specificity of DNA/RGD1-R6 polyplexes were investigated. TheHSV-1thymidine kinase encoding plasmid delivery to PANC-1pancreatic carcinoma cells and primary UL cells resulted in significant suicide gene therapy effects. Subsequent ganciclovir treatment decreased cells proliferative activity, induced of apoptosis and promoted cells death.The obtained results allow us to concludethatthe developed RGD1-R6 carrier can be considered a promising candidate for suicide gene therapy of uterine leiomyoma.

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Section: Introductionmentioning

confidence: 99%

Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma

et al. 2021

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“…We have recently demonstrated that local treatment of glioma with sHDL (synthetic High-density lipoprotein) mimicking nanodiscs containing ApoAI mimetic peptide, phospholipids, immunogenic cell death inducing chemotherapeutics (ICD) docetaxel and adjuvant CpG oligodeoxynucleotide, effectively elicit anti-glioma T-cell activity and induce immunological memory response against tumor relapse (Kadiyala et al, 2019 ). We also engineered an albumin based NPs equipped with cell-penetrating iRGD peptide, containing siRNA against Signal Transducer and Activation of Transcription 3 factor (STAT3 i ) and demonstrated that when administered in combination with ionizing radiation, these NPs activate anti-GBM immunologic memory which results in tumor regression and long term survival of GBM bearing mice (Gregory et al, 2020 ). Other peptide modifications on nano-platforms have been explored to minimize off-target accumulation and facilitate active tumor targeting or mediate BBB transport.…”

Section: Gene Therapy and Virotherapy In Gliomamentioning

confidence: 99%

Current Approaches for Glioma Gene Therapy and Virotherapy

Banerjee

Núñez

Haase

et al. 2021

Front. Mol. Neurosci.

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Glioblastoma (GBM) is the most common and aggressive primary brain tumor in the adult population and it carries a dismal prognosis. Inefficient drug delivery across the blood brain barrier (BBB), an immunosuppressive tumor microenvironment (TME) and development of drug resistance are key barriers to successful glioma treatment. Since gliomas occur through sequential acquisition of genetic alterations, gene therapy, which enables to modification of the genetic make-up of target cells, appears to be a promising approach to overcome the obstacles encountered by current therapeutic strategies. Gene therapy is a rapidly evolving field with the ultimate goal of achieving specific delivery of therapeutic molecules using either viral or non-viral delivery vehicles. Gene therapy can also be used to enhance immune responses to tumor antigens, reprogram the TME aiming at blocking glioma-mediated immunosuppression and normalize angiogenesis. Nano-particles-mediated gene therapy is currently being developed to overcome the BBB for glioma treatment. Another approach to enhance the anti-glioma efficacy is the implementation of viro-immunotherapy using oncolytic viruses, which are immunogenic. Oncolytic viruses kill tumor cells due to cancer cell-specific viral replication, and can also initiate an anti-tumor immunity. However, concerns still remain related to off target effects, and therapeutic and transduction efficiency. In this review, we describe the rationale and strategies as well as advantages and disadvantages of current gene therapy approaches against gliomas in clinical and preclinical studies. This includes different delivery systems comprising of viral, and non-viral delivery platforms along with suicide/prodrug, oncolytic, cytokine, and tumor suppressor-mediated gene therapy approaches. In addition, advances in glioma treatment through BBB-disruptive gene therapy and anti-EGFRvIII/VEGFR gene therapy are also discussed. Finally, we discuss the results of gene therapy-mediated human clinical trials for gliomas. In summary, we highlight the progress, prospects and remaining challenges of gene therapies aiming at broadening our understanding and highlighting the therapeutic arsenal for GBM.

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“… 8 Recently we developed and systemically administered 200 nm albumin-based-NP formulation to treat GBM bearing mice. 9 Our electro-hydrodynamic system is a new NP synthesis technology that can produce albumin-based NPs with distinct compartments. 8 In this system the rapid solvent evaporation induces nanoprecipitation resulting in particles with distinct compartments.…”

Section: Commentarymentioning

confidence: 99%