Cubosome nanoparticles for enhanced delivery of mitochondria anticancer drug elesclomol and therapeutic monitoring via sub-cellular NAD(P) H multi-photon fluorescence lifetime imaging

摘要

Elesclomol (ELC) is an anticancer drug inducing mitochondria cytotoxicity through reactive oxygen species.Here,for the first time,we encapsulate the poorly water soluble ELC in monoolein-based cubosomes stabilized with Pluronic F127.Cellular uptake and nanocarrier accumulation close to the mitochondria with sub-micrometer distance is identified via three-dimensional (3D) confocal microscopy and edge-to-edge compartment analysis.To monitor the therapeutic effect of the ELC nanocarrier,we apply for the first time,label-free time-lapse multi-photon fluorescence lifetime imaging microscopy (MP-FLIM) to track NAD(P)H cofactors with sub-cellular resolution on live cells exposed to an anticancer nanocarrier.Improved in vitro cytotoxicity is verified when loading the pre-complexed ELC with copper (ELC-Cu).Importantly,for equivalent copper concentration,cubosomes loaded with ELC-Cu show higher cytotoxicity compared to the free drug.The novel nanocarrier shows promising features for systemic ELC-Cu administration,and furthermore we establish the MP-FLIM technique for the assessment of anticancer drug delivery systems.