Oxidative stress induced paclitaxel-derived carbon dots inhibit glioblastoma proliferation and EMT process.

Abstract

Glioblastoma represents the most prevalent and deadly form of brain tumor with limited therapeutic drugs. The existence of the blood-brain barrier (BBB) hinders drugs permeate to the brain efficiently. Nowadays, nano-formulations, particularly carbon dots, have emerged as promising candidates for targeting and treating brain diseases. In this study, we report the synthesis of a novel carbon dots, PTX-CDs, using a one-step hydrothermal method with paclitaxel (PTX) as the precursor. PTX-CDs shows increased water solubility by about 1000 times in comparison with PTX. Moreover, PTX-CDs effectively penetrates the BBB and exerts significant anticancer effects. In detail, PTX-CDs accumulates in mitochondria of tumor cells without adding extra targeted molecules, resulting in the damage of mitochondrial membrane potential and increased reactive oxygen species (ROS) level. Transcriptome profiling revealed that PTX-CDs disturbs the cell-cycle by inducing arrest at the G2/M phase, thereby inhibiting cell proliferation. PTX-CDs further decreased cell invasion by inhibiting the epithelial-mesenchymal transition (EMT) process in glioblastoma cells. PTX-CDs significantly inhibited the growth of intracranial tumors in orthotopic glioblastoma mice model and prolonged the survival of tumor-bearing mice. This study presents a viable strategy to develop CDs-based therapeutic agent for glioblastoma using the conventional chemotherapeutic drugs.