Janus Dendrimers as Nanocarriers of Ibuprofen, Chlorambucil and their Anticancer Activity

Janus Dendrimer represents a novel class of synthetic nanocarriers. Since it is possible to introduce multiple drugs and target moieties, this helps the designing of new biocompatible forms with pharmacological activities comprised of different drugs with tailor-made functionalities, such as anticancer and nonsteroidal anti-inflammatory, which could improve the anticancer activity with less toxicity.

This study aimed to determine the anticancer activity of the Janus dendrimers formed by two dendrons. One dendron conjugates with chlorambucil, and the other dendron conjugates with Ibuprofen.

The cytotoxicity of the drug carriers was determined by the sulforhodamine B (SRB) assay for three cell lines. PC-3 (human prostatic adenocarcinoma), HCT-15 (human colorectal adenocarcinoma), MFC-7 (human breast cancer) and the COS-7 African green monkey kidney (used as a control) cell lines were seeded into 96-well plates at a density of 5x10³ cells/well and cultured for 24 h before use. All the obtained compounds were characterized by ¹H and ¹³C NMR one and two dimensions, UVvis, FTIR, MALDI-TOF, Electrospray mass, and FAB+. Microscopic images were taken in an Inverted microscope Nikon, Diaphot 300, 10x4 in culture medium.

Janus dendrimers (G1 and G2) were synthesized via an azide-alkyne click-chemistry reaction attaching on one face dendrons with ibuprofen molecules and, on the other face, attached a chlorambucil- derivative. The IC₅₀ behavior of the conjugates of the first and second generations showed anticancer activity against PC-3, HCT-15, and MFC-7 cell lines. The second generation was more active against PC-3, HCT-15 and MFC-7 with IC₅₀ of 3.8±0.5, 3.0±0.2 and 3.7 ± 1.1 mM, respectively.

The new Janus dendrimers with anticancer chlorambucil and nonsteroidal antiinflammatory Ibuprofen can improve the anticancer activity of chlorambucil with less toxicity.

Now, we are working on the synthesis of new Janus dendrimers using the most effective and fine methods. Moreover, we hope that we shall be able to obtain different generations that are more selective against cancer cells.