As a new class of drug delivery vector with high potential pharmaceutical potential (e.g. anticancer, antibacterial), cell penetrating peptides (CPPs) have been extensive explored. However, the translocating capacity of CPPs is accompanying with severe toxicity effect resulting from perturbation of cell membrane at higher peptide concentration. Early reports found the incorporation of negative charged residue would reduce the cellular toxicity, which achieved at the cost of the reduction of cellular internalization. Herein we designed a phosphate peptide that unable to fold on cell surface and enter cells. The dephosphorylation evens remove the negative charge allows the resultant peptide translocate cell membrane as common CPPs. Because certain cancer cells can overexpress alkaline phosphatase on cell surface, which allows phosphate peptide selectively enter these cancer cells without compromising its translocation ability. On the contrast, much less phosphate peptide enter normal cells since less amount of alkaline phosphatase was expressed on normal cells. Doxorubicin, an extensive used anti-cancer drug in clinical, was choosing to connected to designed CPP. Doxorubicin-peptide conjugate exhibits high selectivity toxicity to cancer cells without harming normal cells. As a first example of cell specific CPP, this work offers a novel approach for target drug delivery and cancer therapy.

Cell dependent cell-penetrating peptides

254th National Meeting (2017)

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