Transplantation of autologous extracellular vesicles for cancer-specific targeting

Nano- and microsized extracellular vesicles (EVs) are naturally occurring cargo-bearing packages of regulatory macromolecules, and recent studies are increasingly showing that EVs are responsible for physiological intercellular communication. Nanoparticles encapsulating anti-tumor theranostics represent an attractive exosome-interfering strategy for cancer therapy. Methods: Herein, by labeling plasma-derived EVs with indocyanine green (ICG) and following their biodistribution by in vivo and ex vivo imaging, we demonstrate the existence of nanoparticles with a highly selective cancer tropism in the blood of colorectal cancer (CRC) patients but not in that of healthy volunteers. Results: In CRC patient-derived xenograft (PDX) mouse models, we show that transplanted EVs recognize tumors from the cognate nanoparticle-generating individual, suggesting the theranostic potential of autologous EVs encapsulating tumor-interfering molecules. In large canine breeds bearing spontaneous malignant skin and breast tumors, the same autologous EV transplantation protocol shows comparable safety and efficacy profiles. Conclusions: Our data show the existence of an untapped resource of intercellular communication present in the blood of cancer patients, which represents an efficient and highly biocompatible way to deliver molecules directly to the tumor with great precision. The novel EV-interfering approach proposed by our study may become a new research direction in the complex interplay of modern personalized cancer therapy.

Automated summary

Research has shown that nano- and microsized extracellular vesicles (EVs) play a significant role in intercellular communication and can be used for targeted cancer therapy. By labeling EVs with indocyanine green (ICG) and tracking their distribution, it was found that nanoparticles with cancer tropism exist in the blood of colorectal cancer (CRC) patients. In mouse models, it was demonstrated that transplanted EVs were able to recognize tumors and deliver tumor-interfering molecules, indicating the therapeutic potential of autologous EVs for cancer treatment.