title: Cancer stem cell therapy using doxorubicin conjugated to gold nanoparticles via hydrazone bonds.
abstract: Nanoparticle-mediated delivery of chemotherapies has demonstrated enhanced anti-cancer efficacy, mainly through the mechanisms of both passive and active targeting. Herein, we report other than these well-elucidated mechanisms, rationally designed nanoparticles can efficiently deliver drugs to cancer stem cells (CSCs), which in turn contributes significantly to the improved anti-cancer efficacy. We demonstrate that doxorubicin-tethered gold nanoparticles via a poly(ethylene glycol) spacer and an acid-labile hydrazone bond mediate potent doxorubicin delivery to breast CSCs, which reduces their mammosphere formation capacity and their cancer initiation activity, eliciting marked enhancement in tumor growth inhibition in murine models. The drug delivery mediated by the nanoparticles also markedly attenuates tumor growth during off-therapy stage by reducing breast CSCs in tumors, while the therapy with doxorubicin alone conversely evokes an enrichment of breast CSCs. Our findings suggest that with well-designed drug delivery system, the conventional chemotherapeutic agents are promising for cancer stem cell therapy.
authors.affiliation: Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, PR China.
authors.forename: Tian-Meng
authors.initials: TM
authors.lastname: Sun
authors.forename: Yu-Cai
authors.initials: YC
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Jin-Zhi
authors.initials: JZ
authors.lastname: Du
authors.forename: Cheng-Qiong
authors.initials: CQ
authors.lastname: Mao
authors.forename: Chun-Yang
authors.initials: CY
authors.lastname: Sun
authors.forename: Rui-Zhi
authors.initials: RZ
authors.lastname: Tang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Zhu
authors.forename: Xian-Zhu
authors.initials: XZ
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005260:Female; D006046:Gold / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016688:Mice, Inbred NOD; D053758:Nanoparticles / Q000737:chemistry*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D006046:Gold; D004317:Doxorubicin
keywords: Breast cancer; Cancer stem cells; Drug delivery; Drug resistance; Gold nanoparticles