Abstract
Carbon dots (CDs), a class of carbon-based nanoparticles smaller than 10 nm, have been widely applied for cancer therapy. Nucleus-targeting CDs, especially cationic carbon dots (CCDs), are regarded as promising nanomaterials for applications in cancer treatment and gene therapy. Developing therapeutic CDs that integrate nucleus-targeting capability with intrinsic anticancer activity can be a promising new research direction in this field. Meanwhile, the development and modification of novel CCDs to obtain gene delivery vehicles with high transfection efficacy offer another valuable strategy for advancing cancer gene therapy. Therefore, this thesis aims to offer the strategies for preparation of CCDs with nucleus-targeting ability for cancer cells inhibition and gene delivery. To achieve this goal, we prepared therapeutic CDs, Y15-CDs, using anticancer agent Y15 (a focal adhesion kinase inhibitor) as one of precursors. The obtained Y15-CDs can bind to DNA through electrostatic, intercalative, and groove binding modes, resulting in cell cycle arrest at the S phase in cancer cells and showing higher cytotoxicity to cancer cells than to normal cells. After optimization and conjugation of Y15-CDs with methotrexate (MTX), the resulting Y15*-CDs-MTX display enhanced inhibitory effects on breast cancer cells compared to Y15*-CDs or MTX alone. For gene delivery, lipid-conjugated CCDs composed of oleic acid (OA) and APCDs derived from arginine (Arg) and pentaethylenehexamine (PEHA) were prepared for plasmid DNA (pDNA) and small interfering RNA (siRNA) delivery. The results demonstrate that all APCDs-OA conjugates show high pDNA transfection efficacy, while APCDs-0.5OA from mass ratio of 1:0.5 exhibit excellent siRNA transfection capability.