Encapsulating anticancer protein therapeutics in nanocarriers is an attractive option to minimize active drug destruction, increase local accumulation at the disease site, and decrease side effects to other tissues. Tumor-specific ligands can further facilitate targeting the nanocarriers to tumor cells and reduce nonspecific cellular internalization. Rationally designed non-covalent protein nanocapsules incorporating copper-free "click chemistry" moieties, polyethylene glycol (PEG) units, redox-sensitive cross-linker, and tumor-specific targeting ligands were synthesized to selectively deliver intracellular protein therapeutics into tumor cells via receptor-mediated endocytosis.
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