Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 461, Issue 1-2, Pages 391-402Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2013.12.011
Keywords
Apoptosis; Dendrimer; Glycodendrimer; PPI; Proliferation; Toxicity
Categories
Funding
- National Science Centre, Poland [DEC2011/01/B/NZ5/01371]
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Since the first dendrimers were synthesized, scientists around the world have studied their properties and potential applications. Cationic dendrimers are characterized by significant toxicity due to their interactions with cells components. The replacement of all cationic surface groups by neutral ones and therefore diminishing positive charge reduces the toxicity but may also lead to loss of dendrimers' desirable properties and restrict their biomedical applications. We have compared the cytotoxicity, as well as proapoptotic and antiproliferative activity of unmodified fourth generation PPI dendrimer (PPI-G4) and dendrimers modified with maltose (Mal) or maltotriose (Mal-III) - for full (dense shell - DS) or partial (open shell - OS) surface modifications. We have proved that among glycodendrimers, the OS-Mal PPI-G4 dendrimer is the most toxic, whereas DS-Mal-III molecule shows relatively weak or even no effect. We have also confirmed that OS dendrimers, both maltotriose and maltose modified, not only reduce cancer cells viability by inducing apoptosis but also inhibit their proliferation. The use of dendrimers as an active substance, which may be a drug per se is one of the most exciting and clinically important applications of cancer nanotechnology, therefore a partial modification of the surface appears to be a perfect solution for this purpose. (C) 2013 Elsevier By. All rights reserved.
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