posted on 2022-01-24, 15:41authored byYifei He, Kaiyuan Wang, Yutong Lu, Bingjun Sun, Jin Sun, Wei Liang
The current state of antitumor nanomedicines
is severely restricted
by poor penetration in solid tumors. It is indicated that extracellular
vesicles (EVs) secreted by tumor cells can mediate the intercellular
transport of antitumor drug molecules in the tumor microenvironment.
However, the inefficient generation of EVs inhibits the application
of this approach. Herein, we construct an EV-mediated self-propelled
liposome containing monensin as the EV secretion stimulant and photosensitizer
pyropheophorbide-a (PPa) as a therapeutic agent. Monensin and PPa
are first transferred to the tumor plasma membrane with the help of
membrane fusogenic liposomes. By hitchhiking EVs secreted by the outer
tumor cells, both drugs are layer-by-layer transferred into the deep
region of a solid tumor. Particularly, monensin, serving as a sustainable
booster, significantly amplifies the EV-mediated PPa penetration by
stimulating EV production. Our results show that this endogenous EV-driven
nanoplatform leads to deep tumor penetration and enhanced phototherapeutic
efficacy.