1. Assembling BH3-mimic peptide into a nanocluster to target intracellular Bcl2 towards the apoptosis induction of cancer cell.
- Author
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Zhang X, Gao R, Yan H, Zhao Z, Zhang J, and You W
- Subjects
- Antineoplastic Agents chemistry, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents pharmacology, Cell Survival drug effects, Gold chemistry, HCT116 Cells, Humans, Nanomedicine, Neoplasms chemistry, Neoplasms metabolism, Apoptosis drug effects, Drug Delivery Systems methods, Metal Nanoparticles chemistry, Peptide Fragments chemistry, Peptide Fragments pharmacokinetics, Peptide Fragments pharmacology, Proto-Oncogene Proteins chemistry, Proto-Oncogene Proteins pharmacokinetics, Proto-Oncogene Proteins pharmacology, Proto-Oncogene Proteins c-bcl-2 metabolism
- Abstract
Bcl-2, an anti-apoptotic protein, is always overexpressed in tumor cells to suppress the pro-apoptotic function of Bax, thereby prolonging the life of the tumor. However, BH3 proteins could directly activate Bax via antagonizing Bcl-2 to induce apoptosis in response to the stimulation. Thus, mimicking BH3 proteins with a peptide is a potential strategy for anti-cancer therapy. Unfortunately, clinical translation of BH3-mimic peptide is hindered by its inefficacious cellular internalization and proteolysis resistance. Herein, we translated a BH3-mimic peptide into a peptide-auric spheroidal nanocluster (BH3-AuNp), in which polymeric BH3-Auric precursors [Au
1+ -S-BH3]n are in situ self-assembled on the surface of gold nanoparticles by a one-pot synthesis. Expectedly, this strategy could improve the anti-proteolytic ability and cytomembrane penetrability of the BH3 peptide. As a result, BH3-AuNp successfully induced the apoptosis of two cancer cell lines by an order of magnitude compared to BH3. This therapeutic and feasible peptide nano-engineering strategy will help peptides overcome the pharmaceutical obstacles, awaken its biological functions, and possibly revive the research about peptide-derived nanomedicine., (© 2021 IOP Publishing Ltd.)- Published
- 2021
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