4.8 Article

Monensin Enhanced Generation of Extracellular Vesicles as Transfersomes for Promoting Tumor Penetration of Pyropheophorbide-a from Fusogenic Liposome

Journal

NANO LETTERS
Volume 22, Issue 3, Pages 1415-1424

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.1c04962

Keywords

membrane fusogenic liposomes; tumor penetration; extracellular vesicle; monensin; photodynamic therapy

Funding

  1. National Natural Science Foundation of China [82073777]
  2. Liaoning Revitalization Talents Program [XLYC180801]
  3. Shenyang Youth Science and Technology Innovation Talents Program [RC190454]

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The penetration of antitumor nanomedicines in solid tumors is limited. However, extracellular vesicles (EVs) secreted by tumor cells can facilitate the intercellular transport of drugs in the tumor microenvironment. The inefficient generation of EVs hinders the application of this approach. Therefore, researchers developed a liposome-based nanoplatform containing a stimulant for EV secretion and a therapeutic agent. This endogenous EV-driven nanoplatform enables deep tumor penetration and enhanced phototherapeutic efficacy.
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.

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