Camptothecin Delivery via Tumor-Derived Exosome for Radiosensitization by Cell Cycle Regulation on Patient-Derived Xenograft Mice

Purpose: While radiotherapy remains the leading clinical treatment for many tumors, its efficacy can be significantly hampered by the insensitivity of cells in the S phase of the cell cycle to such irradiation.Methods: Here, we designed a highly targeted drug delivery platform in which exosomes were loaded with the FDA-approved anti-tumor drug camptothecin (CPT) which is capable of regulating cell cycle. The utilized exosomes were isolated from patient tumors, enabling the personalized treatment of individuals to ensure better therapeutic outcomes.Results: This exosome-mediated delivery strategy was exhibited robust targeted to patient-derived tumor cells in vitro and in established patient-derived xenograft models. By delivering CPT to tumor cells, this nanoplatform was able to decrease cell cycle arrest in the S phase, increasing the frequency of cells in the G1 and G2/M phases such that they were more radiosensitive.Conclusion: This therapeutic approach was able to substantially enhance the sensitivity of patient-derived tumors to ionizing radiation, thereby improving the overall efficacy of radiotherapy without the need for a higher radiation dose.