Urinary exosomes-based Engineered Nanovectors for Homologously Targeted Chemo-Chemodynamic Prostate Cancer Therapy via abrogating EGFR/AKT/NF-kB/IkB signaling

Shaojun Pan; Yuhui Zhang; Mark Huang; Zhoufeng Deng; Amin Zhang; Lijia Pei; Lirui Wang; Weiyong Zhao; Lijun Ma; Qian Zhang; Daxiang Cui

doi:10.1016/j.biomaterials.2021.120946

Urinary exosomes-based Engineered Nanovectors for Homologously Targeted Chemo-Chemodynamic Prostate Cancer Therapy via abrogating EGFR/AKT/NF-kB/IkB signaling

Biomaterials. 2021 Aug:275:120946. doi: 10.1016/j.biomaterials.2021.120946. Epub 2021 Jun 4.

Authors

Shaojun Pan¹, Yuhui Zhang², Mark Huang³, Zhoufeng Deng⁴, Amin Zhang⁵, Lijia Pei⁶, Lirui Wang⁵, Weiyong Zhao⁴, Lijun Ma⁴, Qian Zhang⁷, Daxiang Cui⁸

Affiliations

¹ School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China; Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai, 200240, PR China; First Affiliated Hospital of Bengbu Medical College, Bengbu, 233030, China.
² Department of General Practice, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.
³ School of Electronic Information and Electrical Engineering, Shenzhen University, Shenzhen, 518061, China.
⁴ Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, PR China.
⁵ Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai, 200240, PR China.
⁶ First Affiliated Hospital of Bengbu Medical College, Bengbu, 233030, China.
⁷ Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai, 200240, PR China. Electronic address: qianzhang0130@sjtu.edu.cn.
⁸ School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China; Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai, 200240, PR China. Electronic address: dxcui@sjtu.edu.cn.

PMID: 34119884
DOI: 10.1016/j.biomaterials.2021.120946

Abstract

Multi-functional nanovectors based on exosomes from cancer cell culture supernatants in vitro has been successfully utilized for tumor-specific targeting and immune escape. However, the labor-intensive purification procedures for rich-dose and high-purity homogeneous exosomes without using targeting ligands are still a challenging task. Herein, we developed a nanovector Exo-PMA/Fe-HSA@DOX through cloaked by urinary exosome membrane as a chemo/chemodynamic theranostic nano-platform for targeted homologous prostate cancer therapy which pertain to the abrogation of Epidermal Growth Factor Receptor (EGFR) and its downstream AKT/NF-kB/IkB signaling instead of ERK signaling cascades. Urinary exosomes-based nanovectors own the same urological cancer cell membrane antigen inclusive of E-cadherin, CD 47 and are free from intracellular substance such as Histone 3 and COX Ⅳ. The targeting properties of the homologous cancer cell are well preserved in Exo-PMA/Fe-HSA@DOX nanovectors in high purity. Meanwhile, the nanovectors based on urinary exosomes from prostate patients deeply penetrated into prostate cancer DU145 3D MCTS, and successfully achieve superior synergistic low-dose chemo/chemodynamic performance in vivo. In addition, the blockage of bypassing EGFR/AKT/NF-kB/IkB signaling pathway is greatly enhanced via elevated intracellular PMA/Fe-HSA@DOX nanoparticles (NPs). It is expected that the rich source and high purity of urinary exosomes offer a reliable solution for mass production of such nanovectors in the future. The targeted homologous cancer therapy based on the urinary exosomes from cancer patients exemplifies a novel targeted anticancer scheme with efficient and facile method.

Keywords: Fenton reaction; Nanovectors; Targeted prostate cancer therapy; Urinary exosome.

Publication types

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

MeSH terms

Cell Line, Tumor
ErbB Receptors
Exosomes*
Humans
Male
NF-kappa B
Prostatic Neoplasms* / drug therapy
Proto-Oncogene Proteins c-akt
Signal Transduction

Substances

NF-kappa B
EGFR protein, human
ErbB Receptors
Proto-Oncogene Proteins c-akt