Transplantation of autologous extracellular vesicles for cancer-specific targeting

自体细胞外囊泡移植用于癌症特异性靶向治疗

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作者:Alessandro Villa, Mariangela Garofalo, Daniela Crescenti, Nicoletta Rizzi, Electra Brunialti, Andrea Vingiani, Paolo Belotti, Carlo Sposito, Silvia Franzè, Francesco Cilurzo, Giancarlo Pruneri, Camilla Recordati, Chiara Giudice, Alessia Giordano, Monica Tortoreto, Giangiacomo Beretta, Damiano Stefan

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.

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.

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