Light is an ideal general triggered signal, which occurs as a result of its non-invasive nature, desirable controllability and high spatial resolution. However, due to its low penetrability and ability to harm tissues, the use of ultraviolet (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. In this study, we have devised and tested a strategy for site-specific delivery of small interfering RNA (siRNA) into cancer cells by using liposomes bearing a photolabile-caged peptide (PCP). The positive charges of the lysine residues on the cell-penetrating peptide (CPP) were temporarily caged by the NIR two-photon excitation-responsive protective groups (PG), thereby forming a PCP. Once illuminated by NIR light at tumor tissues, these PGs were cleaved; the positively charged CPP regained its activity and facilitated rapid intracellular delivery of the liposomes into cancer cells. The PCP was connected with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine via a polyethylene glycol (PEG) spacer to prepare the modified liposomes (PCP-LP). Subsequent research demonstrated that the application of the PCP modifications may provide an approach for the selectively targeted delivery of siRNA.
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