title: Selective killing of breast cancer cells expressing activated CD44 using CD44 ligand-coated nanoparticles in vitro and in vivo.
abstract: The cell surface glycoprotein CD44 is expressed in cancer cells and has been used as a therapeutic target in preclinical studies. However, the ubiquitous expression of CD44 in numerous cell types, including hematopoietic cells, has hindered its application in targeted therapy. Here, we demonstrated that CD44 was activated on breast cancer cells but was inactive on normal cells in vitro and in vivo. We analyzed 34 clinical primary tumor and normal breast tissues and demonstrated that CD44 was in an active state on breast cancer cells but in an inactive state on normal cells. Furthermore, based on the binding property of CD44 with its ligand hyaluronan (HA), we self-assembled HA-coated nanoparticles and studied their selective targeting efficacy. Our results indicate that HA-coated nanoparticles bearing the CD44 ligand selectively targeted cancer cells both in vitro and in vivo, killing breast cancer cells while sparing normal cells. Our study suggested that the active state of CD44 plays a crucial role in the selective targeting of breast cancer cells by avoiding nonspecific toxicity to CD44-quiescent normal cells. These findings may provide a new idea for the selective targeting of cancer cells in other human cancers.
authors.affiliation: Department of Molecular Biology Laboratory, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.|Department of Clinical Laboratory, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Molecular Biology Laboratory, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Pathology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Huizhen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biology Laboratory, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology Laboratory, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Molecular Biology Laboratory, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.|Department of Clinical Laboratory, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D004337:Drug Carriers / Q000378:metabolism; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D051379:Mice; D053758:Nanoparticles / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C497483:CD44 protein, human; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D017239:Paclitaxel
keywords: CD44; breast cancer; hyaluronan; selective targeting therapy