Nanotheranostics 2018; 2(4):360-370. doi:10.7150/ntno.27142 This issue Cite

Research Paper

In vivo therapeutic evaluation of polymeric nanomedicines: effect of different targeting peptides on therapeutic efficacy against breast cancer

Yongmei Zhao, Nicholas L. Fletcher, Tianqing Liu, Anna C. Gemmell, Zachary H. Houston, Idriss Blakey, Kristofer J. Thurecht

Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology and ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Queensland, Brisbane, 4072, Australia
QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD, 4006, Australia

Citation:
Zhao Y, Fletcher NL, Liu T, Gemmell AC, Houston ZH, Blakey I, Thurecht KJ. In vivo therapeutic evaluation of polymeric nanomedicines: effect of different targeting peptides on therapeutic efficacy against breast cancer. Nanotheranostics 2018; 2(4):360-370. doi:10.7150/ntno.27142. https://www.ntno.org/v02p0360.htm
Other styles

File import instruction

Abstract

Graphic abstract

Targeted nanomedicines offer many advantages over macromolecular therapeutics that rely only on passive accumulation within the tumour environment. The aim of this work was to investigate the in vivo anticancer efficiency of polymeric nanomedicines that were conjugated with peptide aptamers that show high affinity for receptors on many cancer cells. In order to assess the ability for the nanomedicine to treat cancer and investigate how structure affected the behavior of the nanomedicine, three imaging modalities were utilized, including in vivo optical imaging, multispectral optoacoustic tomography (MSOT) and ex vivo confocal microscopy. An 8-mer (A8) or 13-mer (A13) peptide aptamer that have been shown to exhibit high affinity for heat shock protein 70 (HSP70) was covalently-bound to hyperbranched polymer (HBP) nanoparticles with the purpose of both cellular targeting, as well as the potential to impart some level of chemo-sensitization to the cells. Furthermore, doxorubicin was bound to the polymeric carrier as the anticancer drug, and Cyanine-5.5 (Cy5.5) was incorporated into the polymer as a monomeric fluorophore to aid in monitoring the behavior of the nanomedicine. Enhanced tumour regression was observed in nude mice bearing MDA-MB-468 xenografts when the nanocarriers were targeted using the peptide ligands, compared to control groups treated with free DOX or HBP without aptamer. The accumulated DOX level in solid tumours was 5.5 times higher in mice treated with the targeted therapeutic, than mice treated with free DOX, and 2.6 times higher than the untargeted nanomedicine that relied only on passive accumulation. The results suggest that aptamer-targeted therapeutics have great potential for improving accumulation of nanomedicines in tumours for therapy.

Keywords: peptide aptamers, chemo-sensitization, Multispectral Optoacoustic Tomography (MSOT), nanomedicine


Citation styles

APA
Zhao, Y., Fletcher, N.L., Liu, T., Gemmell, A.C., Houston, Z.H., Blakey, I., Thurecht, K.J. (2018). In vivo therapeutic evaluation of polymeric nanomedicines: effect of different targeting peptides on therapeutic efficacy against breast cancer. Nanotheranostics, 2(4), 360-370. https://doi.org/10.7150/ntno.27142.

ACS
Zhao, Y.; Fletcher, N.L.; Liu, T.; Gemmell, A.C.; Houston, Z.H.; Blakey, I.; Thurecht, K.J. In vivo therapeutic evaluation of polymeric nanomedicines: effect of different targeting peptides on therapeutic efficacy against breast cancer. Nanotheranostics 2018, 2 (4), 360-370. DOI: 10.7150/ntno.27142.

NLM
Zhao Y, Fletcher NL, Liu T, Gemmell AC, Houston ZH, Blakey I, Thurecht KJ. In vivo therapeutic evaluation of polymeric nanomedicines: effect of different targeting peptides on therapeutic efficacy against breast cancer. Nanotheranostics 2018; 2(4):360-370. doi:10.7150/ntno.27142. https://www.ntno.org/v02p0360.htm

CSE
Zhao Y, Fletcher NL, Liu T, Gemmell AC, Houston ZH, Blakey I, Thurecht KJ. 2018. In vivo therapeutic evaluation of polymeric nanomedicines: effect of different targeting peptides on therapeutic efficacy against breast cancer. Nanotheranostics. 2(4):360-370.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image