Exosome-based photoacoustic imaging guided photodynamic and immunotherapy for the treatment of pancreatic cancer.

Affiliation

Jang Y(1), Kim H(2), Yoon S(3), Lee H(1), Hwang J(3), Jung J(1), Chang JH(4), Choi J(5), Kim H(6).
Author information:
(1)Department of Chemical and Biomolecular Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea.
(2)Department of Information and Communication Engineering
(ICE), Daegu Gyeongbuk Institute of Science and Technology
(DGIST), Daegu 42988, South Korea.
(3)School of Integrative Engineering, Chung-Ang University, 84 Heukseok-ro, Seoul 06974, Republic of Korea.
(4)Department of Information and Communication Engineering
(ICE), Daegu Gyeongbuk Institute of Science and Technology
(DGIST), Daegu 42988, South Korea. Electronic address: [Email]
(5)School of Integrative Engineering, Chung-Ang University, 84 Heukseok-ro, Seoul 06974, Republic of Korea. Electronic address: [Email]
(6)Department of Chemical and Biomolecular Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea; Department of Biomedical Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea. Electronic address: [Email]

Abstract

Exosomes, which are released from all cells and take part in cell-to-cell communication, have been utilized as drug delivery vehicles in many recent studies. Immunotherapy is an emerging technology which uses patients' innate immune systems. In immunotherapy, immune cells are stimulated through antibodies, the other immune cells and genetic modifications for the purposes of, for instance, cancer therapy. In this study, tumor-derived re-assembled exosome (R-Exo) was simultaneously utilized as both a drug delivery carrier and an immunostimulatory agent. A chlorin e6 photosensitizer was loaded into tumor-derived exosomes during exosomal re-assembly. After this modification, R-Exo retains its original average size and has the same membrane proteins, which allows for targeting of tumor cells. Chlorin e6-loaded R-Exo (Ce6-R-Exo) can be visualized by photoacoustic imaging and can efficiently generate reactive oxygen species inside tumor cells under laser irradiation. In addition, Ce6-R-Exo increased the release of cytokines from immune cells, which indicates that these modified exosomes can be used as an immunotherapeutic agent. In conclusion, we developed a novel strategy that enables photoacoustic imaging-guided photodynamic and immune-combination therapy for the treatment of cancer with tumor-derived Ce6-R-Exo.