Biosynthesis of Multifunctional Transformable Peptides for Inducing Tumor Cell Apoptosis

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 19; no. 48; pp. e2303035 - n/a
• Main Authors: Di, Yufei, Shen, Qi, Yang, Zhiwen, Song, Gang, Fang, Tiantian, Liu, Yazhou, Liu, Yamei, Luo, Qun, Wang, Fuyi, Yan, Xuehai, Bai, Haotian, Huang, Yiming, Lv, Fengting, Wang, Shu
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01.11.2023
• Subjects: Anticancer properties; Apoptosis; Biosynthesis; Cancer; Cathepsin B; Controllability; Dimerization; E coli; Light irradiation; living materials; Morphology; nanofibers; Nanomaterials; Nanoparticles; Nanotechnology; Peptides; Polyelectrolytes; Proteins; Self-assembly; self‐assembled proteins; transformation; Transformations (mathematics); Tumors
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202303035

Engineered nanomaterials hold great promise to improve the specificity of disease treatment. Herein, a fully protein‐based material is obtained from nonpathogenic Escherichia coli (E. coli), which is capable of morphological transformation from globular to fibrous in situ for inducing tumor cell apoptosis. The protein‐based material P1 is comprised of a β‐sheet‐forming peptide KLVFF, pro‐apoptotic protein BAK, and GFP along with targeting moieties. The self‐assembled nanoparticles of P1 transform into nanofibers in situ in the presence of cathepsin B, and the generated nanofibrils favor the dimerization of functional BH3 domain of BAK on the mitochondrial outer membrane, leading to efficient anticancer activity both in vitro and in vivo via mitochondria‐dependent apoptosis through Bcl‐2 pathway. To precisely manipulate the morphological transformation of biosynthetic molecules in living cells, a spatiotemporally controllable anticancer system is constructed by coating P1‐expressing E. coli with cationic conjugated polyelectrolytes to release the peptides in situ under light irradiation. The biosynthetic peptide‐based enzyme‐catalytic transformation strategy in vivo would offer a novel perspective for targeted delivery and shows great potential in precision disease therapeutics. A biosynthesized protein‐based material is fabricated by non‐pathogenic Escherichia coli (E. coli). The self‐assembled nanoparticles of P1 could transform into nanofibers in situ, which could lead to efficient anticancer activity. Furthermore, a spatiotemporally controllable anticancer system is constructed by coating P1‐expressing E. coli with cationic conjugated polyelectrolytes to release the peptides in situ under light irradiation.