Development of bionanocapsules targeting brain tumors

Tsutsui, Yumi; Tomizawa, Kazuhito; Nagita, Mana; Michiue, Hiroyuki; Nishiki, Tadaaki; Ohmori, Iori; Seno, Masaharu; Matsui, Hideki

doi:10.1016/j.jconrel.2007.06.019

Cited by 72 publications

(53 citation statements)

References 19 publications

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“…Significant anti-analgesic effects in the tail-flick test were observed compared to the control loperamideloaded HSA NPs with IgG2a antibodies therefore demonstrating that the loperamide-MAb-coupled HSA NPs were able to transport this drug and possibly other drugs across the BBB. Tsutsui et al synthesized hybrid bionanocapsules (BNCs), which are hollow NPs that are composed of L protein (the hepatitis B virus surface antigen), conjugated with anti-human EGFR antibody recognizing EGFRvIII, a constitutively active genomic sequence deletion variant of EGFR overexpressed in human glioblastoma [270]. The hybrid BNCs were efficiently delivered to glioma cells but not normal glial cells.…”

Section: Brain Targetingmentioning

confidence: 99%

Antibody-Conjugated Nanoparticles for Therapeutic Applications

Cardoso

Peça²,

Roque³

2012

CMC

110

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Abstract:A great challenge to clinical development is the delivery of chemotherapeutic agents, known to cause severe toxic effects, directly to diseased sites which increase the therapeutic index whilst minimizing off-target side effects. Antibody-conjugated nanoparticles offer great opportunities to overcome these limitations in therapeutics. They combine the advantages given by the nanoparticles with the ability to bind to their target with high affinity and improve cell penetration given by the antibodies. This specialized vehicle, that can encapsulate several chemotherapeutic agents, can be engineered to possess the desirable properties, allowing overcoming the successive physiological conditions and to cross biological barriers and reach a specific tissue or cell. Moreover, antibody-conjugated nanoparticles have shown the ability to be internalized through receptor-mediated endocytosis and accumulate in cells without being recognized by the P-glycoprotein, one of the main mediators of multi-drug resistance, resulting in an increase in the intracellular concentration of drugs. Also, progress in antibody engineering has allowed the manipulation of the basic antibody structure for raising and tailoring specificity and functionality. This review explores recent developments on active drug targeting by nanoparticles functionalized with monoclonal antibodies (polymeric micelles, liposomes and polymeric nanoparticles) and summarizes the opportunities of these targeting strategies in the therapy of serious diseases (cancer, inflammatory diseases, infectious diseases, and thrombosis).

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Section: Brain Targetingmentioning

confidence: 99%

Antibody-Conjugated Nanoparticles for Therapeutic Applications

Cardoso

Peça²,

Roque³

2012

CMC

110

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“…Its high-affinity interaction with the Fc part of antibodies [142,143] has been exploited to generate antibody displaying nanocapsules ( Figure 7A) that were employed for in vitro targeted delivery of proteins [144] for simultaneous detection of multiple antigens in immunological assays (Western blot analysis, immunocytochemistry, flow cytometric analysis, and immunohistochemistry) [145], for immunosensor chips [146,147], or for the establishment of drug-delivery systems [148]. Benhar and co-workers developed FcBD-based ADCs by genetically fusing the ZZ-domain to Pseudomonas exotoxin A (ZZ-PE38) [149].…”

Section: Zz-domainmentioning

confidence: 99%

Antibody Conjugates: From Heterogeneous Populations to Defined Reagents

2015

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Monoclonal antibodies (mAbs) and their derivatives are currently the fastest growing class of therapeutics. Even if naked antibodies have proven their value as successful biopharmaceuticals, they suffer from some limitations. To overcome suboptimal therapeutic efficacy, immunoglobulins are conjugated with toxic payloads to form antibody drug conjugates (ADCs) and with chelating systems bearing therapeutic radioisotopes to form radioimmunoconjugates (RICs). Besides their therapeutic applications, antibody conjugates are also extensively used for many in vitro assays. A broad variety of methods to functionalize antibodies with various payloads are currently available. The decision as to which conjugation method to use strongly depends on the final purpose of the antibody conjugate. Classical conjugation via amino acid residues is still the most common method to produce antibody conjugates and is suitable for most in vitro applications. In recent years, however, it has become evident that antibody conjugates, which are generated via site-specific conjugation techniques, possess distinct advantages with regard to in vivo properties. Here, we give a comprehensive overview on existing and emerging strategies for the production of covalent and non-covalent antibody conjugates.

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“…101 Similar approaches have also been taken with nanoparticle delivery of drugs. 102 In principle, therefore, these techniques can also deliver naked plasmid or viral DNA, potentially in a tumor or tumor vasculature-targeted fashion, to reduce tumor size and/or to kill GBM cells.…”

Section: Therapeutic Approaches To Kill Gbm Cells: Encapsulization Inmentioning

confidence: 99%

Searching for a cure: Gene therapy for glioblastoma

Dent

Yacoub

Park

et al. 2008

Cancer Biology & Therapy

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Glioblastoma multiforme (GBM) is an invariably fatal malignancy. The lethality of GBM has been linked to the highly invasive nature of GBM cells, their escape from immune cell oversight and their high degree of resistance to multiple established therapeutic modalities. The resistance of GBM cells to undergo death processes has, in part, been associated with mutations of specific oncogenes and altered expression of other signaling molecules that lead to reduced capacities to activate multiple apoptosis pathways as well as altered rates of DNA repair and autophagy in response to cytotoxic drugs and cellular stresses. This review will examine how gene therapeutic approaches have been used in the past and are continuing to be used alongside cell signaling modulators and DNA damaging agents as clinical tools to treat GBM. The concerted use of established and novel signal transduction modulatory agents on GBM survival may have potential to lower the apoptotic threshold and facilitate killing in this lethal malignancy.

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Development of bionanocapsules targeting brain tumors

Cited by 72 publications

References 19 publications

Antibody-Conjugated Nanoparticles for Therapeutic Applications

Antibody-Conjugated Nanoparticles for Therapeutic Applications

Antibody Conjugates: From Heterogeneous Populations to Defined Reagents

Searching for a cure: Gene therapy for glioblastoma

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