Abstract
The successful chemotherapeutic regime required for the clinical management of different cancers largely depends on the efficient drug delivery within the cancer cells. Exosomes have emerged as an enticing candidate for exploring their role as delivery vehicles. Exosomes are reported to be intrinsically nanosized vesicles competent for efficient delivery across the cellular membrane. In the present study, we assessed the feasibility of an autologous exosome‐based drug delivery platform for delivering 5‐Fluorouracil (5‐FU) against human colon cancer HCT116 cells. Autologous exosomes have shown probable tropism toward the tumor microenvironment, which makes them the most competitive vehicle for drug delivery. It was observed that the autologous exosomes loaded with 5‐FU showed an enhanced rate of drug release under acidic conditions. The result of the cell viability assay showed that treatment of 5‐FU‐loaded exosomes (equivalent to 5 μg 5‐FU) resulted in enhanced cytotoxic effect in HCT116 cells as compared to an equivalent amount of free 5‐FU (5 μg), which elucidated the efficient delivery of the 5‐FU by exosomes inside the cancer cells. Subsequently, 5‐FU‐loaded exosomes led to increased nuclear condensation and fragmentation along with increased ROS production. In addition, 5‐FU‐loaded exosomes caused enhanced dissipation of mitochondrial membrane potential and caspase‐3 activation, resulting in increased apoptosis induction. Our study also revealed that 5‐FU‐loaded exosomes upsurged the arrest in the cell cycle at the G0/G1 stage in HCT‐116 cells and it was found to be associated with decreased CDK4 and Cyclin D1 expression concomitantly with the upregulation of CDK inhibitor, p21Cip1 expression. Thus, the findings from the present study highlight the advantages of autologous exosomes as a natural drug carrier which could efficiently deliver chemotherapeutic drugs to cancer cells.
Our study evaluated tumor derived exosomes for their potential as drug delivery vehicles. We successfully isolated autologous exosomes from HCT116 cell line colon cancer cells. The drug release profile depicted the effective loading of 5‐Fluorouracil in the autologous exosomes. The anticancer potential of the drug‐loaded exosomes was evaluated through different assays. Our study showed that the treatment of 5‐FU‐loaded exosomes on cancer cells resulted in enhanced cytotoxic effect in HCT‐116 cells when compared to the treatment with equivalent amount of 5‐FU. The study also led to the conclusion that increased nuclear condensation and fragmentation with enhanced ROS production was observed during treatment with 5‐FU‐loaded exosomes. In addition to it, the treatment group with 5‐FU‐loaded exosomes revealed an increased dissipation of mitochondrial membrane potential and caspase 3 activation resulting in apoptosis induction. Our study also revealed that 5‐FU‐loaded exosomes upsurged the arrest in the cell cycle at the G0/G1 stage in HCT‐116 cells and it was found to be associated with decreased CDK4 and Cyclin D1 expression concomitantly with the upregulation of CDK inhibitor, p21Cip1 expression. Thus, the findings from the present study highlight the advantages of autologous exosomes as a natural drug carrier which could efficiently deliver chemotherapeutic drugs to cancer cells.