title: A tumoral acidic pH-responsive drug delivery system based on a novel photosensitizer (fullerene) for in vitro and in vivo chemo-photodynamic therapy.
abstract: Fullerene has shown great potential both in drug delivery and photodynamic therapy. Herein, we developed a doxorubicin (DOX)-loaded poly(ethyleneimine) (PEI) derivatized fullerene (C60-PEI-DOX) to facilitate combined chemotherapy and photodynamic therapy in one system, and DOX was covalently conjugated onto C60-PEI by the pH-sensitive hydrazone linkage. The release profiles of DOX from C60-PEI-DOX showed a strong dependence on the environmental pH value. The biodistributions of C60-PEI-DOX were investigated by injecting CdSe/ZnS (Qds) labeled conjugates (C60-PEI-DOX/Qds) into tumor-bearing mice. C60-PEI-DOX/Qds showed a higher tumor targeting efficiency compared with Qds alone. Compared with free DOX in an in vivo murine tumor model, C60-PEI-DOX afforded higher antitumor efficacy without obvious toxic effects to normal organs owing to its good tumor targeting efficacy and the 2.4-fold greater amount of DOX released in the tumor than in the normal tissues. C60-PEI-DOX also showed high antitumor efficacy during photodynamic therapy. The ability of C60-PEI-DOX nanoparticles to combine local specific chemotherapy with external photodynamic therapy significantly improved the therapeutic efficacy of the cancer treatment, the combined treatment demonstrating a synergistic effect. These results suggest that C60-PEI-DOX may be promising for high treatment efficacy with minimal side effects in future therapy.
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, People's Republic of China.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Shi
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, People's Republic of China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Yu
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, People's Republic of China.
authors.forename: Rou
authors.initials: R
authors.lastname: Ma
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, People's Republic of China.
authors.forename: Ruiyuan
authors.initials: R
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, People's Republic of China. Electronic address: zhangzz08@126.com.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D037741:Fullerenes / Q000737:chemistry / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000378:metabolism; D007834:Lasers; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D009928:Organ Specificity / Q000187:drug effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D037741:Fullerenes; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D011094:Polyethyleneimine
keywords: Fullerene; Nanocarrier; Photodynamic therapy; Synergistic effect; pH-responsive