Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins.

Extracellular vesicles (EVs) are phospholipid-based particles endogenously produced by cells. Their natural composition and selective cell interactions make them promising drug carriers. However, in order to harness their properties, efficient exogenous drug encapsulation methods need to be investigated. Here, EVs from various cellular origins (endothelial, cancer and stem cells) were produced and characterised for size and composition. Porphyrins of different hydrophobicities were employed as model drugs and encapsulated into EVs using various passive and active methods (electroporation, saponin, extrusion and dialysis). Hydrophobic compounds loaded very efficiently into EVs and at significantly higher amounts than into standard liposomes composed of phosphocholine and cholesterol using passive incubation. Moreover, loading into EVs significantly increased the cellular uptake by >60% and the photodynamic effect of hydrophobic porphyrins in vitro compared to free or liposome encapsulated drug. The active encapsulation techniques, with the saponin-assisted method in particular, allowed an up to 11 fold higher drug loading of hydrophilic porphyrins compared to passive methods. EVs loaded with hydrophilic porphyrins induced a stronger phototoxic effect than free drug in a cancer cell model. Our findings create a firm basis for the development of EVs as smart drug carriers based on straightforward and transferable methods.

Fuhrmann G ，Serio A ，Mazo M ，Nair R ，Stevens MM ... -  《-》

Microvesicle- and exosome-mediated drug delivery enhances the cytotoxicity of Paclitaxel in autologous prostate cancer cells.

Extracellular vesicles (EVs) are naturally occurring membrane particles that mediate intercellular communication by delivering molecular information between cells. In this study, we investigated the effectiveness of two different populations of EVs (microvesicle- and exosome-enriched) as carriers of Paclitaxel to autologous prostate cancer cells. EVs were isolated from LNCaP- and PC-3 prostate cancer cell cultures using differential centrifugation and characterized by electron microscopy, nanoparticle tracking analysis, and Western blot. The uptake of microvesicles and exosomes by the autologous prostate cancer cells was assessed by flow cytometry and confocal microscopy. The EVs were loaded with Paclitaxel and the effectiveness of EV-mediated drug delivery was assessed with viability assays. The distribution of EVs and EV-delivered Paclitaxel in cells was inspected by confocal microscopy. Our main finding was that the loading of Paclitaxel to autologous prostate cancer cell-derived EVs increased its cytotoxic effect. This capacity was independent of the EV population and the cell line tested. Although the EVs without the drug increased cancer cell viability, the net effect of enhanced cytotoxicity remained. Both EV populations delivered Paclitaxel to the recipient cells through endocytosis, leading to the release of the drug from within the cells. The removal of EV surface proteins did not affect exosomes, while the drug delivery mediated by microvesicles was partially inhibited. Cancer cell-derived EVs can be used as effective carriers of Paclitaxel to their parental cells, bringing the drug into the cells through an endocytic pathway and increasing its cytotoxicity. However, due to the increased cell viability, the use of cancer cell-derived EVs must be further investigated before any clinical applications can be designed.

Saari H ，Lázaro-Ibáñez E ，Viitala T ，Vuorimaa-Laukkanen E ，Siljander P ，Yliperttula M ... -  《-》

Liposomal Form of Tetra(Aryl)Tetracyanoporphyrazine: Physical Properties and Photodynamic Activity In Vitro.

Yudintsev AV ，Shilyagina NY ，Dyakova DV ，Lermontova SA ，Klapshina LG ，Guryev EL ，Balalaeva IV ，Vodeneev VA ... -  《-》

Association of acenaphthoporphyrins with liposomes for the photodynamic treatment of leishmaniasis.

Gardner DM ，Taylor VM ，Cedeño DL ，Padhee S ，Robledo SM ，Jones MA ，Lash TD ，Vélez ID ... -  《-》

Breast Cancer-Derived Extracellular Vesicles: Characterization and Contribution to the Metastatic Phenotype.

Green TM ，Alpaugh ML ，Barsky SH ，Rappa G ，Lorico A ... -  《-》