Cytotoxicity of PAMAM, PPI and maltose modified PPI dendrimers in Chinese hamster ovary (CHO) and human ovarian carcinoma (SKOV3) cellsThis article is part of the themed issue Dendrimers II, guest-edited by Jean-Pierre Majoral

• Main Authors: Janaszewska, A, Mczyska, K, Matuszko, G, Appelhans, D, Voit, B, Klajnert, B, Bryszewska, M
• Format: Journal Article
• Language: English
• Published: 24.01.2012
• DOI: 10.1039/c1nj20489k
• ISSN: 1144-0546

Characterization of dendrimers as potential therapeutics or drug carriers is complete only when toxicity is assessed. There are numerous studies on the influence of surface modification of PAMAM and PPI dendrimers on their cytotoxic properties but without proposing a mechanism for their toxic effect. In this study cytotoxicity profiles of acid-terminated PAMAM G3.5 and amino-terminated PAMAM G4 in comparison to unmodified amino-terminated PPI-G4 and maltotriose modified PPI-G4 dendrimers were checked. Also the mechanism of cell death in Chinese hamster ovary (CHO) and human ovarian carcinoma (SKOV3) cell lines was investigated. The anionic PAMAM G3.5 dendrimers seem to be the most suitable dendrimers for therapeutic applications, because of their high biocompatibility and low cytotoxicity. Cationic PPI-G4 and PAMAM G4 were the most harmful for both CHO and SKOV3 cell lines, especially in high doses. Maltotriose modification has significantly reduced toxicity within the series of PPI-G4 dendrimers. The moderately doxorubicin and cisplatin resistant human ovarian carcinoma SKOV3 cell line was more vulnerable to modified PPI dendrimers than Chinese hamster ovary CHO cell line which does not show resistance to majority of anticancer agents. This unique property makes these dendrimers potentially interesting for an anticancer therapy. The interaction between dendrimers and mitochondria may cause changes in mitochondrial membrane potential, permeability transition, the generation of intracellular reactive oxygen species and the release of apoptotic proteins. This interaction may eventually lead to cell death.