The clinical application of natural and synthetic amphipathic peptides (e.g., melittin) for cancer therapy is hindered by their notorious side effect, lysing red blood cells. To safely deliver a therapeutic peptide to the tumor tissue and kill cancer cells, we developed an environment-sensitive peptide delivery system, dual secured nano-sting (DSNS), through the combination of a zwitterionic glycol chitosan and disulfide bonds. Melittin loaded DSNS could kill almost 100% of MCF-7, HCT-116, SKOV-3, and NCI/ADR-RES (multidrug resistant) cancer cells at the concentration of 5 μM, while not showing any hemolytic effect.

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