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In Situ Proapoptotic Peptide-Generating Rapeseed Protein-Based Nanocomplexes Synergize Chemotherapy for Cathepsin-B Overexpressing Breast Cancer.

Publication ,  Journal Article
Wang, Z; Zhang, RX; Zhang, T; He, C; He, R; Ju, X; Wu, XY
Published in: ACS Appl Mater Interfaces
December 5, 2018

Intracellular activation of nanomaterials within cancer cells presents a powerful means to enhance anticancer specificity and efficacy. In light of upregulated lysosomal protease cathepsin-B (CathB) in many types of invasive cancer cells, herein, we exploit CathB-catalyzed biodegradation of acetylated rapeseed protein isolate (ARPI) to design polymer-drug nanocomplexes that can produce proapoptotic peptides in situ and synergize chemotherapy. ARPI forms nanocomplexes with chitosan (CS) and anticancer drug doxorubicin (DOX) [DOX-ARPI/CS nanoparticles (NPs)] by ionic self-assembly. The dual acidic pH- and CathB-responsive properties of the nanocomplexes and CathB-catalyzed biodegradation of ARPI enable efficient lysosomal escape and nuclei trafficking of released DOX, resulting in elevated cytotoxicity in CathB-overexpressing breast cancer cells. The ARPI-derived bioactive peptides exhibit synergistic anticancer effect with DOX by regulating pro- and antiapoptotic-relevant proteins ( p53, Bax, Bcl-2, pro-caspase-3) at mitochondria. In an orthotopic breast tumor model of CathB-overexpressing breast cancer, DOX-ARPI/CS NPs remarkably inhibit tumor growth, enhance tumor cell apoptosis and prolong host survival without eliciting any systemic toxicity. These results suggest that exploitation of multifunctional biomaterials to specifically produce anticancer agents inside cancer cells and trigger drug release to the subcellular target sites is a promising strategy for designing effective synergistic nanomedicines with minimal off-target toxicity.

Duke Scholars

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Published In

ACS Appl Mater Interfaces

DOI

EISSN

1944-8252

Publication Date

December 5, 2018

Volume

10

Issue

48

Start / End Page

41056 / 41069

Location

United States

Related Subject Headings

  • Seed Storage Proteins
  • Neoplasm Proteins
  • Nanostructures
  • Nanoscience & Nanotechnology
  • MCF-7 Cells
  • Humans
  • Female
  • Drug Carriers
  • Doxorubicin
  • Cathepsin B
 

Citation

APA
Chicago
ICMJE
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Wang, Z., Zhang, R. X., Zhang, T., He, C., He, R., Ju, X., & Wu, X. Y. (2018). In Situ Proapoptotic Peptide-Generating Rapeseed Protein-Based Nanocomplexes Synergize Chemotherapy for Cathepsin-B Overexpressing Breast Cancer. ACS Appl Mater Interfaces, 10(48), 41056–41069. https://doi.org/10.1021/acsami.8b14001
Wang, Zhigao, Rui Xue Zhang, Tian Zhang, Chunsheng He, Rong He, Xingrong Ju, and Xiao Yu Wu. “In Situ Proapoptotic Peptide-Generating Rapeseed Protein-Based Nanocomplexes Synergize Chemotherapy for Cathepsin-B Overexpressing Breast Cancer.ACS Appl Mater Interfaces 10, no. 48 (December 5, 2018): 41056–69. https://doi.org/10.1021/acsami.8b14001.
Wang Z, Zhang RX, Zhang T, He C, He R, Ju X, et al. In Situ Proapoptotic Peptide-Generating Rapeseed Protein-Based Nanocomplexes Synergize Chemotherapy for Cathepsin-B Overexpressing Breast Cancer. ACS Appl Mater Interfaces. 2018 Dec 5;10(48):41056–69.
Wang, Zhigao, et al. “In Situ Proapoptotic Peptide-Generating Rapeseed Protein-Based Nanocomplexes Synergize Chemotherapy for Cathepsin-B Overexpressing Breast Cancer.ACS Appl Mater Interfaces, vol. 10, no. 48, Dec. 2018, pp. 41056–69. Pubmed, doi:10.1021/acsami.8b14001.
Wang Z, Zhang RX, Zhang T, He C, He R, Ju X, Wu XY. In Situ Proapoptotic Peptide-Generating Rapeseed Protein-Based Nanocomplexes Synergize Chemotherapy for Cathepsin-B Overexpressing Breast Cancer. ACS Appl Mater Interfaces. 2018 Dec 5;10(48):41056–41069.
Journal cover image

Published In

ACS Appl Mater Interfaces

DOI

EISSN

1944-8252

Publication Date

December 5, 2018

Volume

10

Issue

48

Start / End Page

41056 / 41069

Location

United States

Related Subject Headings

  • Seed Storage Proteins
  • Neoplasm Proteins
  • Nanostructures
  • Nanoscience & Nanotechnology
  • MCF-7 Cells
  • Humans
  • Female
  • Drug Carriers
  • Doxorubicin
  • Cathepsin B