title: Chitosan-Decorated Doxorubicin-Encapsulated Nanoparticle Targets and Eliminates Tumor Reinitiating Cancer Stem-like Cells.
abstract: Tumor reinitiating cancer stem-like cells are responsible for cancer recurrence associated with conventional chemotherapy. We developed a doxorubicin-encapsulated polymeric nanoparticle surface-decorated with chitosan that can specifically target the CD44 receptors of these cells. This nanoparticle system was engineered to release the doxorubicin in acidic environments, which occurs when the nanoparticles are localized in the acidic tumor microenvironment and when they are internalized and localized in the cellular endosomes/lysosomes. This nanoparticle design strategy increases the cytotoxicity of the doxorubicin by six times in comparison to the use of free doxorubicin for eliminating CD44(+) cancer stem-like cells residing in 3D mammary tumor spheroids (i.e., mammospheres). We further show these nanoparticles reduced the size of tumors in an orthotopic xenograft tumor model with no evident systemic toxicity. The development of nanoparticle system to target cancer stem-like cells with low systemic toxicity provides a new treatment arsenal for improving the survival of cancer patients.
authors.affiliation: †Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio 43210, United States.|‡Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio 43210, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Rao
authors.affiliation: †Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio 43210, United States.|‡Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio 43210, United States.|§Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.affiliation: §Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States.|∥Division of Hematology, The Ohio State University, Columbus, Ohio 43210, United States.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Han
authors.affiliation: †Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio 43210, United States.|‡Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio 43210, United States.
authors.forename: Shuting
authors.initials: S
authors.lastname: Zhao
authors.affiliation: †Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio 43210, United States.|‡Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio 43210, United States.
authors.forename: Jenna
authors.initials: J
authors.lastname: Dumbleton
authors.affiliation: †Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio 43210, United States.|‡Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio 43210, United States.
authors.forename: Pranay
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: ⊥Biomolecular Engineering Program, Department of Physics and Chemistry, Milwaukee School of Engineering, Milwaukee, Wisconsin 53202, United States.
authors.forename: Wujie
authors.initials: W
authors.lastname: Zhang
authors.affiliation: #Centre for Biomedical Engineering, Department of Electronic Science and Technology, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: §Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States.|∥Division of Hematology, The Ohio State University, Columbus, Ohio 43210, United States.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.affiliation: ∇Division of Genitourinary Pathology, The Ohio State University, Columbus, Ohio 43210, United States.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Zynger
authors.affiliation: ○Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
authors.forename: Xiongbin
authors.initials: X
authors.lastname: Lu
authors.affiliation: †Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio 43210, United States.|‡Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio 43210, United States.|§Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D053758:Nanoparticles / Q000008:administration & dosage*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D048271:Chitosan
keywords: CD44; EPR; cancer stem-like cell; chitosan; nanoparticle; targeting