Pretargeting using peptide nucleic acid

Rusckowski, Mary; Qu, Timothy; Chang, F.; Hnatowich, Donald J.

doi:10.1002/(sici)1097-0142(19971215)80:12+<2699::aid-cncr48>3.3.co;2-a

Cited by 12 publications

(14 citation statements)

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“…, longer motifs with spacers may result in less steric hindrance of binding 148 ), other types of binders such as peptide nucleic acids (PNA), 149,150 locked nucleic acids (LNA), 146,151 and 2′- O -methyloligoribonucleotides (2′-OMe-RNA). 151 …”

Section: Conclusion and Beyondmentioning

confidence: 99%

Drug-free macromolecular therapeutics – a new paradigm in polymeric nanomedicines

Chu

Kopeček

2015

Biomater. Sci.

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This review highlights a unique research area in polymer-based nanomedicine designs. Drug-free macromolecular therapeutics induce apoptosis of malignant cells by the crosslinking of surface non-internalizing receptors. The receptor crosslinking is mediated by the biorecognition of high-fidelity natural binding motifs (such as antiparallel coiled-coil peptides or complementary oligonucleotides) that are grafted to the side chains of polymers or attached to targeting moieties against cell receptors. This approach features the absence of low-molecular-weight cytotoxic compounds. Here, we summarize the rationales, different designs, and advantages of drug-free macromolecular therapeutics. Recent developments of novel therapeutic systems for B-cell lymphomas are discussed, as well as relevant approaches for other diseases. We conclude by pointing out various potential future directions in this exciting new field.

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Section: Conclusion and Beyondmentioning

confidence: 99%

Drug-free macromolecular therapeutics – a new paradigm in polymeric nanomedicines

Chu

Kopeček

2015

Biomater. Sci.

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“…24-26 Nucleic acid hybridization has also been previously used in pre-targeting strategies to assemble targeting agents with imaging agents at the in vivo target site that are aimed at improving specificity. 27-30 In most, cases, nucleic acid hybridization has been used to attach only one functional entity to a nanoparticle. In principle, however, nucleic acid hybridization could also be used as a stable, but reversible, non-covalent click reaction to rapidly and combinatorially assemble much more highly functionalized nanoparticles containing any desired combination of targeting, imaging, therapeutic, endosome disrupting, and stealth functionalities (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Nucleic acid-directed self-assembly of multifunctional gold nanoparticle imaging agents

et al. 2013

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Gold nanoparticles have attracted much interest as a platform for development of multifunctional imaging and therapeutic agents. Multifunctionalized gold nanoparticles are generally constructed by covalent assembly of a gold core with thiolated ligands. In this study, we have assembled multifunctionalized gold nanoparticles in one step by nucleic acid hybridization of ODN (oligodeoxynucleotide)-derivatized gold nanoparticles with a library of pre-functionalized complementary PNAs (peptide nucleic acids). The PNAs were functionalized by conjugation with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) for chelating 64Cu for PET imaging, PEG (polyethylene glycol) for conferring stealth properties, and Cy5 for fluorescent imaging. The resulting nanoparticles showed good stability both in vitro and in vivo showing biodistribution behavior in a mouse that would be expected for a PEGylated gold nanoparticle rather than that for the radiolabelled PNA used in its assembly.

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“…However, these experiments also showed that specific accumulation of radiolabeled PNA derivatives in pretargeted tumor tissue might not be sufficiently high for therapeutic approaches. 33 , 34 , 49 The reason behind it is certainly the rapid elimination of the radiolabeled PNA from blood. The major aim of attaching large PEG moieties onto our 17-mer PNA oligomers was therefore to increase blood retention and subsequently enhance blood availability.…”

Section: Resultsmentioning

confidence: 99%

“…This is in agreements with findings for PNA–streptavidin conjugates circulating in the blood to be able to efficiently bound radiolabeled complementary PNA. 33 …”

Section: Resultsmentioning

confidence: 99%

“…To the best of our knowledge, there is only a single report describing the utilization of PNA–streptavidin bioconjugates for (non-specific) tumor localization in a mouse model by passive diffusion. 33 These PNA–protein conjugates were found to accumulate unspecifically in most tissues of the animals. Consequently, upon administration of the radiolabeled complementary PNA, radioactivity levels were significantly higher compared to control animals.…”

Section: Introductionmentioning

confidence: 99%

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In vivo demonstration of an active tumor pretargeting approach with peptide nucleic acid bioconjugates as complementary system

et al. 2015

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Pretargeting using peptide nucleic acid

Abstract: We conclude that PNA may be considered an alternative to (strept)avidin and biotin for pretargeting studies.

Cited by 12 publications

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Drug-free macromolecular therapeutics – a new paradigm in polymeric nanomedicines

Drug-free macromolecular therapeutics – a new paradigm in polymeric nanomedicines

Nucleic acid-directed self-assembly of multifunctional gold nanoparticle imaging agents

In vivo demonstration of an active tumor pretargeting approach with peptide nucleic acid bioconjugates as complementary system

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