These stimuli-switchable nanoparticles coated with the cleavable outer polymer coatingmultifunctional peptides may afford a new platform for anticancer drugmiR. These nanoparticles possess characteristics of environmental response, active targeting,gene/chemo combinatorial therapeutics, thus providing spatiotemporal control of posttranｓｃｒｉｐｔional gene regulation, smart nuclear/mitochondrial localization,simultaneous inhibition of multiple progression pathways of tumor cells for enhancing antitumor efficacysafety of cancer therapy.

Two characteristics:
(1) The advantage of using pH-sensitive imine bond: The coating of nanoparticles has a long-chain PEG derivative with acid-sensitive imine bond, thus protecting the targeting peptides from degradation in the blood circulation. The imine bond can be hydrolyzeddetached to expose the targeting/penetrating peptides.
(2) The specificity of the peptide sequence: These peptides can target surface receptors of cancers to increase tumor penetration. The targeting peptides may promote localization into the nucleusmitochondria of cancer cells to trigger cell apoptosis.

This combination has the following industrial application potential: These three peptides can not only promote the target of nanoparticle to colorectal cancer, pancreatic cancer,headneck cancer, but also increase the penetration of chemo-gene therapeutics into cancer cells. They may further target the nucleusmitochondria to induce cancer cell apoptosis. In colorectal cancer-headneck cancer-bearing mice, our formulations display better anti-tumor effectlower (or the same) toxicity to non-tumor tissues than those of Onivyde.

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