From the past decade, extracellular vesicles (EVs) have attracted considerable attention as tools for the selective delivery of anti-neoplastic drugs to cancer tissues. Compared to other nanoparticles, EVs display interesting unique features including immune compatibility, low toxicity and the ability to encapsulate a large variety of small- and macro-molecules. However, in virtually all studies, investigations on EVs have been focused on fully transformed cancers: the possibility to apply EV technology also to early-stage tumors has never been explored. Methods: Herein, we studied the ability of cancer-derived EVs to recognize and deliver their cargo also to incipient cancers. To this purpose, EV biodistribution was studied in MMTV-NeuT genetically modified mice during early mammary transformation, in fully developed breast tumors and in the normal gland of wild type syngeneic mice. EVs were loaded with indocyanine green (ICG), a near-infrared (NIR) dye together with oncolytic viruses and i.v. injected in mice. The nanoparticle biodistribution was assayed by in vivo and ex vivo optical imaging (detecting the ICG) and semiquantitative real-time PCR (measuring the adenoviral genome) in different tissues. Results: Our results demonstrate the ability of cancer-derived EVs to recognize early-stage neoplastic tissues opening the possibility to selectively deliver theranostics also for tumor prevention. Conclusions: Taken together our study demonstrates the ability of EVs to recognize and deliver diagnostic and therapeutic agents not only to fully transformed tissues but also to early stage tumors. These findings pave the way for the synthesis of “universal” EVs-based formulation for targeted cancer therapy.

Cancer-derived EVs show tropism for tissues at early stage of neoplastic transformation / M. Garofalo, A.M.G. Villa, E.A.S. Brunialti, D. Crescenti, G. Dell'Omo, L. Kuryk, A. Vingiani, V.M. Mazzaferro, P. Ciana. - In: NANOTHERANOSTICS. - ISSN 2206-7418. - 5:1(2021), pp. 1-7. [10.7150/ntno.47226]

Cancer-derived EVs show tropism for tissues at early stage of neoplastic transformation

M. Garofalo
Co-primo
;
A.M.G. Villa
Co-primo
Conceptualization
;
E.A.S. Brunialti
Secondo
;
D. Crescenti;G. Dell'Omo;A. Vingiani;V.M. Mazzaferro
Penultimo
;
P. Ciana
Ultimo
Conceptualization
2021

Abstract

From the past decade, extracellular vesicles (EVs) have attracted considerable attention as tools for the selective delivery of anti-neoplastic drugs to cancer tissues. Compared to other nanoparticles, EVs display interesting unique features including immune compatibility, low toxicity and the ability to encapsulate a large variety of small- and macro-molecules. However, in virtually all studies, investigations on EVs have been focused on fully transformed cancers: the possibility to apply EV technology also to early-stage tumors has never been explored. Methods: Herein, we studied the ability of cancer-derived EVs to recognize and deliver their cargo also to incipient cancers. To this purpose, EV biodistribution was studied in MMTV-NeuT genetically modified mice during early mammary transformation, in fully developed breast tumors and in the normal gland of wild type syngeneic mice. EVs were loaded with indocyanine green (ICG), a near-infrared (NIR) dye together with oncolytic viruses and i.v. injected in mice. The nanoparticle biodistribution was assayed by in vivo and ex vivo optical imaging (detecting the ICG) and semiquantitative real-time PCR (measuring the adenoviral genome) in different tissues. Results: Our results demonstrate the ability of cancer-derived EVs to recognize early-stage neoplastic tissues opening the possibility to selectively deliver theranostics also for tumor prevention. Conclusions: Taken together our study demonstrates the ability of EVs to recognize and deliver diagnostic and therapeutic agents not only to fully transformed tissues but also to early stage tumors. These findings pave the way for the synthesis of “universal” EVs-based formulation for targeted cancer therapy.
Extracellular vesicles, oncolytic viruses, early-stage cancer therapy, drug delivery, in vivo imaging
Settore BIO/14 - Farmacologia
Settore BIO/10 - Biochimica
   Dipartimenti di Eccellenza 2018-2022 - Dipartimento di ONCOLOGIA ED EMATO-ONCOLOGIA
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
2021
20-set-2020
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/777196
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