title: A redox-sensitive micelle-like nanoparticle self-assembled from amphiphilic adriamycin-human serum albumin conjugates for tumor targeted therapy.
abstract: The application of chemotherapeutic drug adriamycin (ADR) in cancer therapy is limited by its side effects like high toxicity and insolubility. Nanomedicine offers new hope for overcoming the shortcomings. But how to increase in vivo stability and to control intracellular drug release is a key issue for nano-based formulations. Herein, the hydrophobic ADR was successfully linked to the biocompatible human serum albumin (HSA) by disulfide bond 3-(2-pyridyldithio) propionyl hydrazide (PDPH), resulting in amphiphilic HSA-ADR. The novel ADR-HSA micellar NPs which were thus assembled exhibited a well-defined stable core shell structure with glutathione (GSH) sensitive linkers. The stable PDPH linkers at extracellular level were broken by GSH at intracellular level with a controlled ADR release profile. The in vitro cytotoxicity against gastric cancer cells (NCI-N87) was obviously enhanced by such redox-sensitive ADR-HSA NPs. Additionally, as observed by IVIS Lumina II Imaging System (Xenogen), the intratumor accumulation of ADR-HSA NPs was much higher than that of HSA/ADR NPs due to its high stability. Consequently, the in vivo tumor inhibition was significantly promoted after intravenous administration to the Balb/c nude mice bearing gastric tumors. These in vitro/vivo results indicated that disulfide-bond-containing ADR-HSA NPs were an effective nanodrug delivery system for cancer therapy.
authors.affiliation: Department of Medical Oncology, East Hospital, Tongji University, 150 Jimo Road, Shanghai 200120, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
authors.forename: Mengxin
authors.initials: M
authors.lastname: Zhao
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
authors.forename: Xiandi
authors.initials: X
authors.lastname: Zhu
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
authors.forename: Changhong
authors.initials: C
authors.lastname: Ke
authors.affiliation: Department of Orthopaedics, Changzheng Hospital, The Second Military Medical University, No. 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Jiangming
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics, Shanghai 200062, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yan
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
authors.forename: Fulei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China.
authors.forename: Xianxian
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, East Hospital, Tongji University, 150 Jimo Road, Shanghai 200120, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
authors.forename: Shangjing
authors.initials: S
authors.lastname: Guo
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D012709:Serum Albumin; D004317:Doxorubicin