Clickable protein nanocapsules for targeted delivery of recombinant p53 protein

Muxun Zhao, Yarong Liu, Renee S. Hsieh, Nova Wang, Wanyi Tai, Kye Il Joo, Pin Wang, Zhen Gu, Yi Tang

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

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. These nanocapsules can be conjugated to different targeting ligands of choice, such as anti-Her2 antibody single-chain variable fragment (scFv) and luteinizing hormone releasing hormone (LHRH) peptide, resulting in specific and efficient accumulation within tumor cells overexpressing corresponding receptors. LHRH-conjugated nanocapsules selectively delivered recombinant human tumor suppressor protein p53 and its tumor-selective supervariant into targeted tumor cells, which led to reactivation of p53-mediated apoptosis. Our results validate a general approach for targeted protein delivery into tumor cells using cellular-responsive nanocarriers, opening up new opportunities for the development of intracellular protein-based anticancer treatment.

Original languageEnglish
Pages (from-to)15319-15325
Number of pages7
JournalJournal of the American Chemical Society
Volume136
Issue number43
DOIs
StatePublished - 29 Oct 2014

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