Tumor-oriented nanocarrier
drug delivery approaches with photo-sensitivity have been drawing considerable attention over the years. Here we described a nanostructured
lipid carrier (NLC) modified with photo-responsive
cell-penetrating peptides (
pCPP-NLC). The conventional
cell penetrating peptide (
CPP)-mediated intracellular drug delivery system sometimes seemed limited due to the lack of target selectivity of the cell penetrating activity. In this study,
pCPP (CKRRMK(Nvoc)WK(Nvo0c)K(Nvoc)), a photo-responsive
CPP originated from the
CPP (CKRRMKWKK), was endowed photo-responsiveness after masking of lysines in the sequence of
CPP with photolabile-protective groups, and was introduced onto the surface of NLC. Accordingly, upon reaching the
tumor tissues,
pCPP-NLC enhance specific
cancer cellular uptake after rapidly cleaving the photolabile-protective group, in this case, illumination in the presence of UV-light. In contrast, in circulation, the penetration was shielded. The
pCPP-NLC carrying
paclitaxel (PTX) prepared in this work possessed suitable physiochemical properties such as small particle size, high
drug encapsulation efficiency, and good stability. The strong cellular uptake and cytotoxic activity of
pCPP-NLC in HT-1080 cells verified the correlation with illumination. The remarkable penetration into HT-1080 multicellular
tumor spheroids confirmed that the temporary mask of the photolabile-protective group in
pCPP does not disturb the penetration ability of
CPP in the tumor microenvironment with illumination. Furthermore, the triggered activation exhibited higher antitumor efficacy with the
tumor spheroids compared with the non-modified NLC (N-NLC) and
Taxol(®). In conclusion, the application of
pCPP modifications may be an approach for the selectively targeted delivery of anti-
tumor agents.