Multi-component Polymeric System for Tumour Cell-Specific Gene Delivery Using a Universal Bungarotoxin Linker

Willemsen, Ralph A.; Pechar, Michal; Carlisle, Robert; Schooten, E. van; Pola, Robert; Thompson, Amber; Seymour, Leonard W.; Ulbrich, Karel

doi:10.1007/s11095-010-0088-8

Cited by 16 publications

(16 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using a universal bungarotoxin (BTX) linker, non-covalent and non-destructive attachment of a recombinant Ab fragment to pHPMA-modified Ad vectors has been introduced (151). The principle of this strategy is based on the strong and non-covalent interaction between acetylcholine receptors and a-BTX.…”

Section: Active Targetingmentioning

confidence: 99%

Enhancing the therapeutic efficacy of adenovirus in combination with biomaterials

Kim¹,

Kim²,

Kim³

et al. 2012

Biomaterials

View full text Add to dashboard Cite

With the reason that systemically administered adenovirus (Ad) is rapidly extinguished by innate/adaptive immune responses and accumulation in liver, in vivo application of the Ad vector is strictly restricted. For achieving to develop successful Ad vector systems for cancer therapy, the chemical or physical modification of Ad vectors with polymers has been generally used as a promising strategy to overcome the obstacles. With polyethylene glycol (PEG) first in order, a variety of polymers have been developed to shield the surface of therapeutic Ad vectors and well accomplished to extend circulation time in blood and reduce liver toxicity. However, although polymer-coated Ads can successfully evacuate from a series of guarding systems in vivo and locate within tumors by enhanced permeability and retention (EPR) effect, the possibility to entering into the target cell is few and far between. To endow targeting moiety to polymer-coated Ad vectors, a diversity of ligands such as tumor-homing peptides, growth factors or antibodies, have been introduced with avoiding unwanted transduction and enhancing therapeutic efficacy. Here, we will describe and classify the characteristics of the published polymers with respect to Ad vectors. Furthermore, we will also compare the properties of variable targeting ligands, which are being utilized for addressing polymer-coated Ad vectors actively.

show abstract

Section: Active Targetingmentioning

confidence: 99%

Enhancing the therapeutic efficacy of adenovirus in combination with biomaterials

Kim¹,

Kim²,

Kim³

et al. 2012

Biomaterials

View full text Add to dashboard Cite

show abstract

“…The application of protein A or G has allowed antibodies or ligands bearing the Fc domain of immunoglobulin to be linked to therapeutics with high affinity whilst preserving receptor binding regions (17,18). Similar strategies have also been reported utilising the even higher affinity interaction between bungarotoxin and its ligand (19). …”

Section: Introductionmentioning

confidence: 58%

“…The reported difficulties of synthesising and using sialyl Lewis(X) (36) and our previous experience comparing anti-selectin antibodies to the PSGL1 ligand for retargeting of adenovirus vectors (17) persuaded us that the PSGL1 ligand would provide optimal ease of use, efficiency of targeting and reduced immunogenicity. Previous studies have also demonstrated the advantage of attaching targeting ligand to therapeutic agent in ways that use epitopes of the ligand that are not involved in receptor binding and achieve appropriate orientation of the ligand (37) (19). To meet this requirement we developed a new protein G-streptavidin biomaterial as a linker between biotin on the liposome surface and Fc regions in the PSGL1.…”

Section: Discussionmentioning

confidence: 99%

Targeting of Liposomes via PSGL1 for Enhanced Tumor Accumulation

2012

Self Cite

View full text Add to dashboard Cite

PurposeTo improve the delivery of liposomes to tumors using P-selectin glycoprotein ligand 1 (PSGL1) mediated binding to selectin molecules, which are upregulated on tumorassociated endothelium.MethodsPSGL1 was orientated and presented on the surface of liposomes to achieve optimal selectin binding using a novel streptavidin-protein G linker molecule. Loading of PSGL1 liposomes with luciferin allowed their binding to e-selectin and activated HUVEC to be quantified in vitro and their stability, pharmacokinetics and tumor accumulation to be tested in vivo using murine models.ResultsPSGL1 liposomes showed 5-fold (p < 0.05) greater selectin binding than identically formulated control liposomes modified with ligand that did not contain the selectin binding domain. When added to HUVEC, PSGL1 liposomes showed >7-fold (p < 0.001) greater attachment than control liposomes. In in vivo studies PSGL1 liposomes showed similar stability and circulation to control liposomes but demonstrated a >3-fold enhancement in the level of delivery to tumors (p < 0.05).ConclusionsThe technologies and strategies described here may contribute to clinical improvements in the selectivity and efficacy of liposomal drug delivery agents.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-012-0875-5) contains supplementary material, which is available to authorized users.

show abstract

“…Although several sophisticated methods to achieve the site‐specific covalent modification of proteins have been recently described, the formation of a specific noncovalent bond between two peptide tags is an equally attractive approach. Among the various noncovalent methods, the utilization of coiled coil heterodimers, the hybridization of complementary morpholino oligonucleotides and the formation of a complex between bungarotoxin and a bungarotoxin‐binding peptide for the attachment of biologically active proteins to polymer carriers are particularly notable.…”

Section: Introductionmentioning

confidence: 99%

Polymer Cancerostatics Targeted with an Antibody Fragment Bound via a Coiled Coil Motif: In Vivo Therapeutic Efficacy against Murine BCL1 Leukemia

Pechar

Pola

Janoušková

et al. 2017

Macromolecular Bioscience

Self Cite

View full text Add to dashboard Cite

A BCL1 leukemia‐cell‐targeted polymer–drug conjugate with a narrow molecular weight distribution consisting of an N‐(2‐hydroxypropyl)methacrylamide copolymer carrier and the anticancer drug pirarubicin is prepared by controlled radical copolymerization followed by metal‐free click chemistry. A targeting recombinant single chain antibody fragment (scFv) derived from a B1 monoclonal antibody is attached noncovalently to the polymer carrier via a coiled coil interaction between two complementary peptides. Two pairs of coiled coil forming peptides (abbreviated KEK/EKE and KSK/ESE) are used as linkers between the polymer–pirarubicin conjugate and the targeting protein. The targeted polymer conjugate with the coiled coil linker KSK/ESE exhibits 4× better cell binding activity and 2× higher cytotoxicity in vitro compared with the other conjugate. Treatment of mice with established BCL1 leukemia using the scFv‐targeted polymer conjugate leads to a markedly prolonged survival time of the experimental animals compared with the treatment using the free drug and the nontargeted polymer–pirarubicin conjugate.

show abstract

Multi-component Polymeric System for Tumour Cell-Specific Gene Delivery Using a Universal Bungarotoxin Linker

Abstract: We have shown that the presented Ad-PHPMA-BTXbp/scFv-BTX system can be used as a universal tool for a receptor-specific virotherapy.

Cited by 16 publications

References 20 publications

Enhancing the therapeutic efficacy of adenovirus in combination with biomaterials

Enhancing the therapeutic efficacy of adenovirus in combination with biomaterials

Targeting of Liposomes via PSGL1 for Enhanced Tumor Accumulation

Polymer Cancerostatics Targeted with an Antibody Fragment Bound via a Coiled Coil Motif: In Vivo Therapeutic Efficacy against Murine BCL1 Leukemia

Contact Info

Product

Resources

About