Trastuzumab-grafted PAMAM dendrimers for the selective delivery of anticancer drugs to HER2-positive breast cancer

Kulhari, H, Pooja, D, Shrivastava, S, Kuncha, M, Naidu, V, Bansal, V, Sistla, R and Adams, D 2016, 'Trastuzumab-grafted PAMAM dendrimers for the selective delivery of anticancer drugs to HER2-positive breast cancer', Scientific Reports, vol. 6, 23179, pp. 1-13.


Document type: Journal Article
Collection: Journal Articles

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Title Trastuzumab-grafted PAMAM dendrimers for the selective delivery of anticancer drugs to HER2-positive breast cancer
Author(s) Kulhari, H
Pooja, D
Shrivastava, S
Kuncha, M
Naidu, V
Bansal, V
Sistla, R
Adams, D
Year 2016
Journal name Scientific Reports
Volume number 6
Article Number 23179
Start page 1
End page 13
Total pages 13
Publisher Nature Publishing Group
Abstract Approximately 20% of breast cancer cases are human epidermal growth factor receptor 2 (HER2)-positive. This type of breast cancer is more aggressive and tends to reoccur more often than HER2-negative breast cancer. In this study, we synthesized trastuzumab (TZ)-grafted dendrimers to improve delivery of docetaxel (DTX) to HER2-positive breast cancer cells. Bioconjugation of TZ on the surface of dendrimers was performed using a heterocrosslinker, MAL-PEG-NHS. For imaging of cancer cells, dendrimers were also conjugated to fluorescein isothiocyanate. Comparative in vitro studies revealed that these targeted dendrimers were more selective, and had higher antiproliferation activity, towards HER2-positive MDA-MB-453 human breast cancer cells than HER2-negative MDA-MB-231 human breast cancer cells. When compared with unconjugated dendrimers, TZ-conjugated dendrimers also displayed higher cellular internalization and induction of apoptosis against MDA-MB-453 cells. Binding of TZ to the dendrimer surface could help site-specific delivery of DTX and reduce systemic toxicity resulting from its lack of specificity. In addition, in vivo studies revealed that the pharmacokinetic profile of DTX was significantly improved by the conjugated nanosystem.
Subject Nanomedicine
Cancer Therapy (excl. Chemotherapy and Radiation Therapy)
Characterisation of Biological Macromolecules
DOI - identifier 10.1038/srep23179
Copyright notice This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.
ISSN 2045-2322
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