Liposomal Gene Therapy with the Herpes Simplex Thymidine Kinase Gene/Ganciclovir System for the Treatment of Glioblastoma Multiforme

Voges, Jürgen; Weber, Friedrich; Reszka, Regina; Sturm, Volker; Heiss, Wolf‐Dieter; Wiestler, Ottmar; Kapp, Joachim Friedrich

doi:10.1089/10430340252837260

Cited by 29 publications

(3 citation statements)

References 43 publications

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“…and Zhou et al . showed that even following CED, the ECM acts as a diffusion barrier limiting the spatial distribution of therapeutic nanoparticles [19, 47–48]. Therefore, the diffusion and distribution of therapeutics within the brain and brain tumors is a major limitation to achieving significant treatment efficacy, even with these local therapeutic approaches.…”

Section: Discussionmentioning

confidence: 99%

Minimizing the non-specific binding of nanoparticles to the brain enables active targeting of Fn14-positive glioblastoma cells

et al. 2015

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A major limitation in the treatment of glioblastoma (GBM), the most common and deadly primary brain cancer, is delivery of therapeutics to invading tumor cells outside of the area that is safe for surgical removal. A promising way to target invading GBM cells is via drug-loaded nanoparticles that bind to fibroblast growth factor-inducible 14 (Fn14), thereby potentially improving efficacy and reducing toxicity. However, achieving broad particle distribution and nanoparticle targeting within the brain remains a significant challenge due to the adhesive extracellular matrix (ECM) and clearance mechanisms in the brain. In this work, we developed Fn14 monoclonal antibody-decorated nanoparticles that can efficiently penetrate brain tissue. We show these Fn14-targeted brain tissue penetrating nanoparticles are able to (i) selectively bind to recombinant Fn14 but not brain ECM proteins, (ii) associate with and be internalized by Fn14-positive GBM cells, and (iii) diffuse within brain tissue in a manner similar to non-targeted brain penetrating nanoparticles. In addition, when administered intracranially, Fn14-targeted nanoparticles showed improved tumor cell co-localization in mice bearing human GBM xenografts compared to non-targeted nanoparticles. Minimizing non-specific binding of targeted nanoparticles in the brain may greatly improve the access of particulate delivery systems to remote brain tumor cells and other brain targets.

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Section: Discussionmentioning

confidence: 99%

Minimizing the non-specific binding of nanoparticles to the brain enables active targeting of Fn14-positive glioblastoma cells

et al. 2015

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“…In addition to modification to non-viral vectors, other techniques like pressure-driven flow provided by convection enhanced delivery (CED) have been explored in conjunction with non-viral vectors to improve their diffusion in the brain. 28,60–62 These methods may aid in more widespread and evenly distributed delivery across the brain, as well as improved permeation in glioblastomas During CED, fine intracranial catheters are implanted and deliver therapeutics along a pressure gradient from the catheter tip and extracellular space allowing for controlled and homogenous distribution throughout the injection area. 28 Research in this area has highlighted the importance of specific vector properties, such as sub-100 nm size and neutral or anionic surface charge in order to adequately utilize CED as steric hindrance or electrostatic binding can't be overcome via CED.…”

Section: Strategies Investigatedmentioning

confidence: 99%

Overcoming barriers in non-viral gene delivery for neurological applications

et al. 2022

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“…In general, the studies on gene therapy for GBM follow one of two approaches: (1) Suicide gene therapy using the herpes simplex thymidine kinase (HSV-tk) to sensitize tumor cells to ganciclovir (GCV) [ 108 - 110 ] or (2) Immune gene therapy using cytokine genes. Preclinical studies of interferon β (INF-β) and human interlukin 12 (IL-12) gene transfer using liposomes displayed positive results [ 111 - 114 ], and clinical studies have been warranted or already performed [ 115 - 118 ]. Moreover, for liposomal gene therapy, a hybrid vector of HVJ-liposome (HVJ: hemagglutinating virus of Japan or Sendai virus) has been developed [ 119 ], which can fuse with cellular plasma membrane, releasing the contents into the cytoplasm, in contrast to usual liposome vectors that are taken up into cells by endocytosis.…”

Section: Introductionmentioning

confidence: 99%

Nanotechnology Applications for Diffuse Intrinsic Pontine Glioma

Bredlau¹,

Dixit²,

Chen³

et al. 2017

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Diffuse intrinsic pontine gliomas (DIPGs) are invariably fatal tumors found in the pons of elementary school aged children. These tumors are grade II-IV gliomas, with a median survival of less than 1 year from diagnosis when treated with standard of care (SOC) therapy. Nanotechnology may offer therapeutic options for the treatment of DIPGs. Multiple nanoparticle formulations are currently being investigated for the treatment of DIPGs. Nanoparticles based upon stable elements, polymer nanoparticles, and organic nanoparticles are under development for the treatment of brain tumors, including DIPGs. Targeting of nanoparticles is now possible as delivery techniques that address the difficulty in crossing the blood brain barrier (BBB) are developed. Theranostic nanoparticles, a combination of therapeutics and diagnostic nanoparticles, improve imaging of the cancerous tissue while delivering therapy to the local region. However, additional time and attention should be directed to developing a nanoparticle delivery system for treatment of the uniformly fatal pediatric disease of DIPG.

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Liposomal Gene Therapy with the Herpes Simplex Thymidine Kinase Gene/Ganciclovir System for the Treatment of Glioblastoma Multiforme

Cited by 29 publications

References 43 publications

Minimizing the non-specific binding of nanoparticles to the brain enables active targeting of Fn14-positive glioblastoma cells

Minimizing the non-specific binding of nanoparticles to the brain enables active targeting of Fn14-positive glioblastoma cells

Overcoming barriers in non-viral gene delivery for neurological applications

Nanotechnology Applications for Diffuse Intrinsic Pontine Glioma

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