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Polymers 2018, 10(2), 187; https://doi.org/10.3390/polym10020187

Conjugate of PAMAM Dendrimer, Doxorubicin and Monoclonal Antibody—Trastuzumab: The New Approach of a Well-Known Strategy

1
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland
2
Department of Surgical Oncology, Cancer Center, Copernicus Memorial Hospital, 93-509 Lodz, Poland
3
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-236 Lodz, Poland
4
Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Strasse 6, 01069 Dresden, Germany
*
Author to whom correspondence should be addressed.
Received: 18 January 2018 / Revised: 9 February 2018 / Accepted: 12 February 2018 / Published: 14 February 2018
(This article belongs to the Special Issue Polymers for Therapy and Diagnostics)
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Abstract

The strategy utilizing trastuzumab, a humanized monoclonal antibody against human epidermal growth receptor 2 (HER-2), as a therapeutic agent in HER-2 positive breast cancer therapy seems to have advantage over traditional chemotherapy, especially when given in combination with anticancer drugs. However, the effectiveness of single antibody or antibody conjugated with chemotherapeutics is still far from ideal. Antibody–dendrimer conjugates hold the potential to improve the targeting and release of active substance at the tumor site. In the present study, we developed and synthesized PAMAM dendrimer–trastuzumab conjugates carrying doxorubicin (dox) specifically to cells overexpressing HER-2. 1HNMR, FTIR and RP-HPLC were used to characterize the products and analyze their purity. Toxicity of PAMAM–trastuzumab and PAMAM–dox–trastuzumab conjugates compared with free trastuzumab and doxorubicin towards HER-2 positive (SKBR-3) and negative (MCF-7) human breast cancer cell lines was determined using MTT assay. Furthermore, the cellular uptake and cellular localization were studied by flow cytometry and confocal microscopy, respectively. A cytotoxicity profile of above mentioned compounds indicated that conjugate PAMAM–dox–trastuzumab was more effective when compared to free drug or the conjugate PAMAM–trastuzumab. Moreover, these results reveal that trastuzumab can be used as a targeting agent in PAMAM–dox–trastuzumab conjugate. Therefore PAMAM–dox–trastuzumab conjugate might be an interesting proposition which could lead to improvements in the effectiveness of drug delivery systems for tumors that overexpress HER-2. View Full-Text
Keywords: PAMAM dendrimer; trastuzumab; HER-2; doxorubicin; tumor targeting PAMAM dendrimer; trastuzumab; HER-2; doxorubicin; tumor targeting
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Marcinkowska, M.; Sobierajska, E.; Stanczyk, M.; Janaszewska, A.; Chworos, A.; Klajnert-Maculewicz, B. Conjugate of PAMAM Dendrimer, Doxorubicin and Monoclonal Antibody—Trastuzumab: The New Approach of a Well-Known Strategy. Polymers 2018, 10, 187.

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