Asymmetric peptide dendrimers are effective linkers for antibody-mediated delivery of diverse payloads to B cells in vitro and in vivo

Shah, Neha D., Parekh, Harendra S. and Steptoe, Raymond J. (2014) Asymmetric peptide dendrimers are effective linkers for antibody-mediated delivery of diverse payloads to B cells in vitro and in vivo. Pharmaceutical Research, 31 11: 3150-3160. doi:10.1007/s11095-014-1408-1

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Author Shah, Neha D.
Parekh, Harendra S.
Steptoe, Raymond J.
Title Asymmetric peptide dendrimers are effective linkers for antibody-mediated delivery of diverse payloads to B cells in vitro and in vivo
Journal name Pharmaceutical Research   Check publisher's open access policy
ISSN 0724-8741
1573-904X
Publication date 2014-05-22
Year available 2014
Sub-type Article (original research)
DOI 10.1007/s11095-014-1408-1
Open Access Status
Volume 31
Issue 11
Start page 3150
End page 3160
Total pages 11
Place of publication New York, NY, United States
Publisher Springer New York
Collection year 2015
Language eng
Formatted abstract
Purpose Safe, targeted delivery of therapeutics remains a focus of drug/gene delivery, the aim being to achieve optimal efficacy while minimising off-target delivery. Dendrimers have a vast array of potential applications and have great potential as gene and drug delivery tools. We previously reported the development of peptide dendrimers that effectively complexed DNA and that have distinct advantages over conventional spherical dendrimers. Here, to expand the application of peptide-based low generation dendrimers we tested their capacity to be transformed into linkers for antibody-based targeting of diverse payloads.

Methods Peptide-based low-generation asymmetric dendrimers were generated and conjugated to partially-reduced antibodies specific for B cell surface antigens or an irrelevant antigen. Preservation of antigen binding by the antibodies and targeting of the conjugated dendrimers carrying a small molecule (biotin) or plasmid DNA payloads was tested.

Results Peptide-based low generation dendrimers were efficiently and site-specifically conjugated to antibodies with retention of antigen-binding capacity. Altering the branching termini of dendrimers facilitated delivery of diverse payloads in vitro and in vivo.

Conclusions We propose that safe, non-toxic peptide dendrimers, which are readily synthesised and modifiable for a variety of applications, form the basis of a new family of biocompatible “linkers” with substantial potential for targeted delivery applications.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 22 May 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Pharmacy Publications
UQ Diamantina Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 4 times in Scopus Article | Citations
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Created: Wed, 27 Aug 2014, 20:00:43 EST by Harendra Parekh on behalf of UQ Diamantina Institute