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

doi:10.1016/j.biomaterials.2022.121488

Oncolytic peptide nanomachine circumvents chemo resistance of renal cell carcinoma

Biomaterials. 2022 May:284:121488. doi: 10.1016/j.biomaterials.2022.121488. Epub 2022 Mar 29.

Authors

Jia Yang¹, Rui Zheng¹, Muhetaerjiang Mamuti¹, Da-Yong Hou², Yong-Dan Zhao¹, Hong-Wei An³, Hao Wang⁴, Yuliang Zhao⁵

Affiliations

¹ CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Haidian District, Beijing, 100190, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Haidian District, Beijing, 100190, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, PR China.
² CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Haidian District, Beijing, 100190, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Haidian District, Beijing, 100190, China.
³ CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Haidian District, Beijing, 100190, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Haidian District, Beijing, 100190, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, PR China. Electronic address: anhw@nanoctr.cn.
⁴ CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Haidian District, Beijing, 100190, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Haidian District, Beijing, 100190, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, PR China. Electronic address: wanghao@nanoctr.cn.
⁵ CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Haidian District, Beijing, 100190, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Haidian District, Beijing, 100190, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, PR China. Electronic address: zhaoyl@nanoctr.cn.

PMID: 35367840
DOI: 10.1016/j.biomaterials.2022.121488

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.

Keywords: Cancer therapy; Morphology transformation; Nanomaterials; Peptides; Self-assembly.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Renal Cell* / therapy
Cell Line, Tumor
Female
Humans
Kidney Neoplasms* / therapy
Male
Oncolytic Virotherapy* / methods
Oncolytic Viruses* / physiology
Peptides / chemistry
Tumor Microenvironment

Substances

Peptides