Oncolytic peptide nanomachine circumvents chemo resistance of renal cell carcinoma

Jia Yang, Rui Zheng, Muhetaerjiang Mamuti, Da Yong Hou, Yong Dan Zhao, Hong Wei An, Hao Wang, Yuliang Zhao

Research output: Contribution to journalArticlepeer-review

Abstract

Due to intrinsic and acquired chemo/radiotherapy-resistance, renal cell carcinoma shows limited therapeutic response to clinically utilized targeting drugs. Here a tumor-activated oncolytic peptide nanomachine is devised to selectively lysing tumor cell membrane without causing drug resistance. Specifically, in the acidic tumor microenvironment, the oncolytic peptide nanomachine automatically activated through morphologically transformation from nanoparticles to nanofibrils with restoring α-helical conformation, which physically bind to tumor cell membrane with multiple (spatially correlated and time-resolved) interactions and subsequently lyse local cell membrane. The IC50 of the oncolytic peptide nanomachine is as low as 2.44 μM and it inhibit up to 90% of tumor cells within 2 h with unique bystander killing effect. In vivo, the tumor inhibition rate of the oncolytic peptide nanomachine is 71% without off-target activity and hemolytic activity. These results support that tumor-selective oncolytic peptide nanomachine represent a promising alternative approach for multidrug-resistant tumor treatments by inducing cell membrane lysis.

Original languageEnglish (US)
Article number121488
JournalBiomaterials
Volume284
DOIs
StatePublished - May 2022

Keywords

  • Cancer therapy
  • Morphology transformation
  • Nanomaterials
  • Peptides
  • Self-assembly

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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