Tumour-oriented nanocarrier drug delivery approaches with photo-sensitivity have been drawing considerable attention over the years. However, due to its low penetrability and ability to induce tissue damage, the use of UV light for triggered nanocarrier release in in vivo applications has been limited. Compared with UV light, near-infrared (NIR) light deeply penetrates tissues and is less damaging to cells. Here, we report on the development of a novel method employing photo-sensitive cell-penetrating peptides (CPPs), which can be used to trigger the transport of liposomes into cells following stimulation, which was irradiation with NIR light in this case. The positive charges of the lysine residues on the CPP were temporarily caged by a NIR two-photon excitation-responsive protective group (PG), thereby forming photo-sensitive peptides (PSPs). The PSP was connected with DSPE via a polyethylene glycol (PEG) spacer to prepare the modified liposomes (PSP-L). Once illuminated by NIR light in tumour tissues, these PGs were cleaved, and the positively charged CPP regained its activity and facilitated rapid intracellular delivery of the liposomes into cancer cells. The PSP-L carrying vinorelbine bitartrate prepared in this work possessed suitable physiochemical properties. In addition, strong cellular uptake and cytotoxic activity of PSP-L in MCF-7 cells were correlated with NIR illumination. Furthermore, triggered NIR activation of PSP-L led to higher antitumour efficacy in the MCF-7 tumour model in nude mice compared with the unmodified liposomes (N-L). In conclusion, the application of PSP modifications to drug-carrying liposomes may provide an approach for the targeted delivery of antitumour agents.
Keywords: Cell-penetrating peptides; Drug delivery; Liposomes; Near-infrared (NIR) two-photon photolysis; Photo-sensitive peptides.
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