Journal
NANO LETTERS
Volume 20, Issue 8, Pages 5844-5852Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.0c01757
Keywords
chiral supraparticles; protein-protein interactions; miniature protein; D-enantiomerization; p53
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Funding
- The Young Talent Support Plan of Xi'an Jiaotong University
- Thousand Talents Plan of Shaanxi Province
- Institutional Science Foundation of The First Affiliated Hospital of Xi'an Jiaotong University [2019QN-01]
- Postdoctoral innovation talent support program [BX20190278]
- Natural Science Basic Research Plan in Shaanxi Province of China [2020JQ-092]
- Fundamental Research Funds for the Central Universities [1191319101]
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The design of bioactive supramolecular chirality is always hampered by the lack of feasible schemes to assigned specific biological activities. Herein, we developed a mirror-image peptide grafting method to graft the epitopes of bioactive D-peptide onto the miniprotein template to construct a self-assembled supraparticle. Grafting (PMI beta)-P-D, a 12-mer D-enantiomeric peptide functioned as the p53 agonist, onto Apamin, we successfully constructed a self-assembled D-enantiomeric miniprotein supermolecule nanoparticle, termed (MSN)-M-D. This chiral supraparticle possesses a favorable pharmaceutical profile including - the passive tumor targeting, cell membrane penetration, intra-cellular reductive responsiveness, and endosome escaping. (MSN)-M-D showed in vitro and in vivo p53-dependent antiproliferative activity and augmented antitumor immunity elicited by anti-PD1 therapy. This enabling strategy will allow us to fabricate a class of peptide/protein-derived supramolecular chirality with predictable biological activities and will likely have a broad impact on the chiral nanotechnology at the service of prevention and treatment of human diseases.
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