Using peptide aptamer targeted polymers as a model nanomedicine for investigating drug distribution in cancer nanotheranostics

Zhao, Yongmei, Houston, Zachary H., Simpson, Joshua D., Chen, Liyu, Fletcher, Nicholas L., Fuchs, Adrian V., Blakey, Idriss and Thurecht, Kristofer J. (2017) Using peptide aptamer targeted polymers as a model nanomedicine for investigating drug distribution in cancer nanotheranostics. Molecular Pharmaceutics, 14 10: 3539-3549. doi:10.1021/acs.molpharmaceut.7b00560

Author Zhao, Yongmei
Houston, Zachary H.
Simpson, Joshua D.
Chen, Liyu
Fletcher, Nicholas L.
Fuchs, Adrian V.
Blakey, Idriss
Thurecht, Kristofer J.
Title Using peptide aptamer targeted polymers as a model nanomedicine for investigating drug distribution in cancer nanotheranostics
Journal name Molecular Pharmaceutics   Check publisher's open access policy
ISSN 1543-8392
Publication date 2017-09-07
Year available 2017
Sub-type Article (original research)
DOI 10.1021/acs.molpharmaceut.7b00560
Open Access Status Not yet assessed
Volume 14
Issue 10
Start page 3539
End page 3549
Total pages 11
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Subject 1313 Molecular Medicine
3003 Pharmaceutical Science
3002 Drug Discovery
Abstract Theranostics is a strategy that combines multiple functions such as targeting, stimulus-responsive drug release, and diagnostic imaging into a single platform, often with the aim of developing personalized medicine.1,2 Based on this concept, several well-established hyperbranched polymeric theranostic nanoparticles were synthesized and characterized as model nanomedicines to investigate how their properties affect the distribution of loaded drugs at both the cell and whole animal levels. An 8-mer peptide aptamer was covalently bound to the periphery of the nanoparticles to achieve both targeting and potential chemosensitization functionality against heat shock protein 70 (Hsp70). Doxorubicin was also bound to the polymeric carrier as a model chemotherapeutic drug through a degradable hydrazone bond, enabling pH-controlled release under the mildly acid conditions that are found in the intracellular compartments of tumor cells. In order to track the nanoparticles, cyanine-5 (Cy5) was incorporated into the polymer as an optical imaging agent. In vitro cellular uptake was assessed for the hyperbranched polymer containing both doxorubicin (DOX) and Hsp70 targeted peptide aptamer in live MDA-MB-468 cells, and was found to be greater than that of either the untargeted, DOX-loaded polymer or polymer alone due to the specific affinity of the peptide aptamer for the breast cancer cells. This was also validated in vivo with the targeted polymers showing much higher accumulation within the tumor 48 h postinjection than the untargeted analogue. More detailed assessment of the nanomedicine distribution was achieved by directly following the polymeric carrier and the doxorubicin at both the in vitro cellular level via compartmental analysis of confocal images of live cells and in whole tumors ex vivo using confocal imaging to visualize the distribution of the drug in tumor tissue as a function of distance from blood vessels. Our results indicate that this polymeric carrier shows promise as a cancer theranostic, demonstrating active targeting to tumor cells with the capability for simultaneous drug release.
Keyword Cyanine-5
Drug delivery
Hsp70 targeted aptamer
Simultaneous drug release
Theranostic nanoparticles
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1099321
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Australian Institute for Bioengineering and Nanotechnology Publications
Centre for Advanced Imaging Publications
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Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 03 Nov 2017, 16:18:04 EST