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Biomimetic Nanomedicine Coupled with Neoadjuvant Chemotherapy to Suppress Breast Cancer Metastasis via Tumor Microenvironment Remodeling
Authors:Hai-jun Liu  Junfeng Wang  Mingming Wang  Yuzhen Wang  Shanshan Shi  Xiangxiang Hu  Quanguang Zhang  Daping Fan  Peisheng Xu
Affiliation:1. Department of Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, 715 Sumter, Columbia, SC, 29208 USA;2. Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, 6439 Garners Ferry Rod, Columbia, SC, 29209 USA;3. Department of Neuroscience & Regenerative Medicine, Medical College of Georgia at Augusta University, 1120 15th St., Augusta, GA, 30912 USA
Abstract:The biomimetic enzyme activity of cerium oxide nanoparticles (CeNPs) prefers ultrasmall particle size and bare surface. Unfortunately, those two features are not favorable for its in vivo application due to easy aggregation and fast renal filtration. To take advantage of the activity of CeNP for cancer therapy, a homologous targeted cerium oxide nanoparticle system, targeted CeNP (T-CeNP), with the integration of a biodegradable dendritic mesoporous silica nanoparticle, superoxide dismutase and catalase mimicking CeNPs, and the camouflage coating of cancer cell membrane has been developed. Attributed to the homologous targeting effect of cancer cell membrane, nanoparticles with camouflage coating are retained in the tumor in an orthotopic breast cancer metastatic model. Subsequently, T-CeNP effectively hinders cancer-associated fibroblast transdifferentiation and reprograms it back to a normal fibroblast. Consequently, T-CeNP coupled with doxorubicin reduces the size of primary tumors and prevents the post-surgery lung metastasis and liver metastasis of breast cancer.
Keywords:cancer metastasis  cancer-associated fibroblast  cerium oxide nanoparticle  homologous targeting  tumor microenvironment
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