Cell-penetrating peptides (CPPs) have been successfully used for intracellular delivery of a broad variety of cargoes including various nanoparticulate pharmaceutical carriers (liposomes, micelles, nanoparticles, polymer-conjugates). However the cationic nature of all CPP sequences and thus lack of cell-specificity limits their in vivo use for drug delivery applications.
• A novel strategy for site-specific delivery of drugs to tumor cells by using polymers bearing light activated caged Cell-penetrating peptides (cCPP) has been developed.
• Illuminated by UV-light, the CPP facilitate rapid intracellular delivery of polymer-drug conjugates into tumor cells.
• As little as ten minutes of illumination is sufficient to enhance the penetration of polymer-drug conjugates into 80% of the target cells to promote a 'switch' like cytotoxic activity.
• As little as ten minutes of illumination is sufficient to obtain a shift from 100% to 10% in cell viability within as little as 2 h following the illumination.
• This report is the first example for tumor targeting by means of light activation of cell-penetrating peptides for intracellular drug delivery.
Illumination time and dose dependence of the cell viability of PC-3 cell incubated with 80µM (solid blue), 40µM (dashed blue), 20µM (dots blue) P(cCPP)-drug conjugate; 80µM drug alone (solid green), 80µM P-(cCPP) without drug (solid red), as determined by MTT assay.