Assessment of Dendrigrafts of Poly- l -lysine Cytotoxicity and Cell Penetration in Cancer Cells

This work provides an in vitro methodology to assess the cytotoxicity and cell penetration of dendrigrafts of poly- l -lysine (DGLs) in order to select the best molecules to be further tested in preclinical models as nanoscale drug carriers for cancer treatment. The data obtained indicate that, despite their higher molecular weight, DGLs cause cytotoxicity close to that published for other dendrimers (half maximal inhibitory concentration (IC 50 ) > 100 nM up to 1.5 μM depending on the DGL generation and the colon cancer cell line). Besides, the uptake of DGLs by cancer cells was observed within 5 min through a clathrin-dependent process. At a concentration at least 10-fold lower than the IC 50 (10 nM), 60–80% of colon cancer cells internalized DGL-G3, -G4, and -G5 within 4 h, while a cell penetration efficiency of 20–60% was observed for DGL-G2. Finally, DGL cytotoxicity was significantly decreased by serum components. This methodology provides robust data to guide DGL functionalization to further reduce DGL cytotoxicity and safely address anticancer drugs to cancer cells and represents a standardized and easy-to-use approach to characterize nanovectors for biological applications.