AUTHOR=Yang Yiling , Ren Shiqi , Huang Wenpeng , Dong Jiahan , Guo Jiancheng , Zhao Jie , Zhang Yonggao 

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

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2022.876641

DOI=10.3389/fbioe.2022.876641

ISSN=2296-4185

ABSTRACT=<p><bold>Purpose:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> This exosome-mediated delivery strategy was exhibited robust targeted to patient-derived tumor cells <italic>in vitro</italic> 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.</p><p><bold>Conclusion:</bold> 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.</p>