title: Co-delivery of all-trans-retinoic acid and doxorubicin for cancer therapy with synergistic inhibition of cancer stem cells.
abstract: Combination treatment through simultaneous delivery of two or more drugs with nanoparticles has been demonstrated to be an elegant and efficient approach for cancer therapy. Herein, we employ a combination therapy for eliminating both the bulk tumor cells and the rare cancer stem cells (CSCs) that have a high self-renewal capacity and play a critical role in cancer treatment failure. All-trans-retinoic acid (ATRA), a powerful differentiation agent of cancer stem cells and the clinically widely used chemotherapy agent doxorubicin (DOX) are simultaneously encapsulated in the same nanoparticle by a single emulsion method. It is demonstrated that ATRA and DOX simultaneous delivery-based therapy can efficiently deliver the drugs to both non-CSCs and CSCs to differentiate and kill the cancer cells. Differentiation of CSCs into non-CSCs can reduce their self-renewal capacity and increase their sensitivity to chemotherapy; with the combined therapy, a significantly improved anti-cancer effect is demonstrated. Administration of this combinational drug delivery system can markedly augment the enrichment of drugs both in tumor tissues and cancer stem cells, prodigiously enhancing the suppression of tumor growth while reduce the incidence of CSC in a synergistic manner.
authors.affiliation: Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Sun
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230026, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230026, China.
authors.forename: Shi-Yong
authors.initials: SY
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230026, China.
authors.forename: Song
authors.initials: S
authors.lastname: Shen
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230026, China.
authors.forename: Xiao-Jiao
authors.initials: XJ
authors.lastname: Du
authors.affiliation: Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Cong-Fei
authors.initials: CF
authors.lastname: Xu
authors.affiliation: Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Zhi-Ting
authors.initials: ZT
authors.lastname: Cao
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230026, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Bao
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230026, China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Zhu
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230026, China.
authors.forename: Xian-Zhu
authors.initials: XZ
authors.lastname: Yang
authors.affiliation: Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China; CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui 230026, China; High Magnetic Field Laboratory of CAS, University of Science and Technology of China, Hefei, Anhui 230026, China. Electronic address: jwang699@ustc.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010316:Particle Size; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D055672:Static Electricity; D014212:Tretinoin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D014212:Tretinoin; D004317:Doxorubicin
keywords: All-trans-retinoic acid; Cancer stem cell; Co-delivery; Combination therapy; Doxorubicin