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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\u2010based drug delivery platform for delivering 5\u2010Fluorouracil (5\u2010FU) 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\u2010FU showed an enhanced rate of drug release under acidic conditions. The result of the cell viability assay showed that treatment of 5\u2010FU\u2010loaded exosomes (equivalent to 5\u00a0\u03bcg 5\u2010FU) resulted in enhanced cytotoxic effect in HCT116 cells as compared to an equivalent amount of free 5\u2010FU (5\u00a0\u03bcg), which elucidated the efficient delivery of the 5\u2010FU by exosomes inside the cancer cells. Subsequently, 5\u2010FU\u2010loaded exosomes led to increased nuclear condensation and fragmentation along with increased ROS production. In addition, 5\u2010FU\u2010loaded exosomes caused enhanced dissipation of mitochondrial membrane potential and caspase\u20103 activation, resulting in increased apoptosis induction. Our study also revealed that 5\u2010FU\u2010loaded exosomes upsurged the arrest in the cell cycle at the G0\/G1 stage in HCT\u2010116 cells and it was found to be associated with decreased CDK4 and Cyclin D1 expression concomitantly with the upregulation of CDK inhibitor, p21<jats:sup>Cip1<\/jats:sup> 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.<\/jats:p>","DOI":"10.1111\/cbdd.14205","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T14:13:39Z","timestamp":1674051219000},"page":"962-976","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["High therapeutic efficacy of <scp>5\u2010Fluorouracil<\/scp>\u2010loaded exosomes against colon cancer cells"],"prefix":"10.1111","volume":"101","author":[{"given":"Rafia","family":"Shekh","sequence":"first","affiliation":[{"name":"Department of Biosciences Integral University  Kursi Road India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afza","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Biosciences Integral University  Kursi Road 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