DNA Damage and P53-Mediated Growth Arrest in Human Cells Treated with Platinum Nanoparticles

Abstract

Saponin fractions of Quillaja saponaria Molina (QS) have cytotoxic activity against cancer cells in vitro, but are too toxic to be useful in the clinic. The toxic effect was abolished by converting QS fractions into stable nanoparticles through the binding of QS to cholesterol. Two fractions of QS were selected for particle formation, one with an acyl-chain (ASAP) was used to form killing and growth-inhibiting (KGI) particles, and the other without the acyl-chain (DSAP) was used to formulate blocking and balancing effect (BBE) particles. KGI showed significant growth inhibiting and cancer cell-killing activities in nine of 10 cell lines while BBE showed that on one cell line. The monoblastoid lymphoma cell line U937 was selected for analyzing the mode of action. Low concentrations of KGI (0.5 and 2 μg/mL) induced irreversible exit from the cell cycle, differentiation measured by cytokine production, and eventually programmed cell death (apoptosis). Compared to normal human monocytes, the U937 cells were 30-fold more sensitive to KGI. The nontoxic BBE blocked the cell killing effect of KGI in a concentration-dependent manner. In conclusion, the formulation of QS into nanoparticles has the potential of becoming a new class of anticancer agents.

First proof of bismuth oxide nanoparticles as efficient radiosensitisers on highly radioresistant cancer cells

“…Investigations into gold NPs [4][5][6][7] and Platinum [8,9] NPs were performed to quantify the biocompatibility of the proposed nanomaterials.…”

Low Dose of Amino-Modified Nanoparticles Induces Cell Cycle Arrest

“…[4][5][6][7][8] Although several nanoparticles accumulate in cells with no acute toxicity, 3,9 some nanomaterials have been found to impact cells and this has generated nanosafety concerns. [10][11][12][13] Cytotoxic responses have been associated to nanoparticles such as metal oxide ones and fullerenes, [14][15][16][17][18] where the effect can be connected mainly to the release of toxic ions due to particle solubility, 19 oxidative stress, 17,20,21 and cationic damage. 20 Recent studies have shown that alterations of the native structure of the proteins that adsorb on the nanoparticles' surface in the context of biological fluids can trigger signaling cascades and activate inflammatory responses.…”

The formation of intracellular nanoparticles correlates with cisplatin resistance

“…In contrast, the cytotoxicity of Pt-NPs is quite limited [34][35][36][37][38][39][40]. Therefore, the conversion of internalized cisplatin molecules into Pt-NPs within cells might have contributed to the apparent drug resistance with tumor cells, which often express high levels of antioxidant enzymes such as GST [22][23][24].…”