Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer Therapy
Dong-Bing Cheng,
Xue-Hao Zhang,
Yuanfang Chen,
Hao Chen,
Zeng-Ying Qiao,
Hao Wang
Affiliations
Dong-Bing Cheng
CAS Center for Excellence in Nanoscience, Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China
Xue-Hao Zhang
CAS Center for Excellence in Nanoscience, Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China; College of Science, Huazhong Agricultural University, Wuhan 430070, China
Yuanfang Chen
CAS Center for Excellence in Nanoscience, Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China
Hao Chen
College of Science, Huazhong Agricultural University, Wuhan 430070, China
Zeng-Ying Qiao
CAS Center for Excellence in Nanoscience, Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China; Corresponding author
Hao Wang
CAS Center for Excellence in Nanoscience, Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China
Summary: In some malignant tumor, especially for pancreatic tumor, poor solid-tumor penetration of nanotherapeutics impedes their treatment efficacy. Herein, we develop a polymer-peptide conjugate with the deep tissue penetration ability, which undergoes a cascade process under ultrasound (US), including (1) the singlet oxygen 1O2 is generated by P18, (2) the thioketal bond is cleaved by the 1O2, (3) the departure of PEG chains leads to the in situ self-assembly, and (4) the resultant self-assembled PK nanoparticles show considerable cellular internalization. Owing to the synergistic effect of US on increasing the membrane permeability, the endocytosis and lysosome escape of PK nanoparticles are further enhanced effectively, resulting in the improved therapeutic efficacy. Thanks to the high tissue-penetrating depth and spatial precision of US, PTPK presents enhanced tumor inhibition in an orthotopic pancreatic tumor model. Therefore, the US-activated cascade effect offers a novel perspective for precision medicine and disease theranostics.
