title: Co-delivery of doxorubicin and curcumin by pH-sensitive prodrug nanoparticle for combination therapy of cancer.
abstract: Ample attention has focused on cancer drug delivery via prodrug nanoparticles due to their high drug loading property and comparatively lower side effects. In this study, we designed a PEG-DOX-Cur prodrug nanoparticle for simultaneous delivery of doxorubicin (DOX) and curcumin (Cur) as a combination therapy to treat cancer. DOX was conjugated to PEG by Schiff's base reaction. The obtained prodrug conjugate could self-assemble in water at pH 7.4 into nanoparticles (PEG-DOX NPs) and encapsulate Cur into the core through hydrophobic interaction (PEG-DOX-Cur NPs). When the PEG-DOX-Cur NPs are internalized by tumor cells, the Schiff's base linker between PEG and DOX would break in the acidic environment that is often observed in tumors, causing disassembling of the PEG-DOX-Cur NPs and releasing both DOX and Cur into the nuclei and cytoplasma of the tumor cells, respectively. Compared with free DOX, free Cur, free DOX-Cur combination, or PEG-DOX NPs, PEG-DOX-Cur NPs exhibited higher anti-tumor activity in vitro. In addition, the PEG-DOX-Cur NPs also showed prolonged blood circulation time, elevated local drug accumulation and increased tumor penetration. Enhanced anti-tumor activity was also observed from the PEG-DOX-Cur-treated animals, demonstrating better tumor inhibitory property of the NPs. Thus, the PEG-DOX-Cur prodrug nanoparticle system provides a simple yet efficient approach of drug delivery for chemotherapy.
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science &Peking Union Medical College. Tianjin 300192, P.R. China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science &Peking Union Medical College. Tianjin 300192, P.R. China.
authors.forename: Cuihong
authors.initials: C
authors.lastname: Yang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, P.R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science &Peking Union Medical College. Tianjin 300192, P.R. China.
authors.forename: Jinjian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science &Peking Union Medical College. Tianjin 300192, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science &Peking Union Medical College. Tianjin 300192, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Huang
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science &Peking Union Medical College. Tianjin 300192, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Chu
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science &Peking Union Medical College. Tianjin 300192, P.R. China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Gao
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, P.R. China.
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.affiliation: Department of Urology, Tianjin First Central Hospital, Tianjin 300192, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science &Peking Union Medical College. Tianjin 300192, P.R. China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Liu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy*; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D011355:Prodrugs; D004317:Doxorubicin; D003474:Curcumin