title: pH- and NIR light responsive nanocarriers for combination treatment of chemotherapy and photodynamic therapy.
abstract: The side effects of antitumor drugs and low treatment efficacy are two major challenges of current chemotherapy. To address these issues, we developed a new kind of smart nanocarriers that combine pH-responsive chemotherapy and near-infrared (NIR) light triggered photodynamic therapy. These nanocarriers were based on upconversion nanoparticle (UCN)-loaded folate-conjugated polymeric lipid vesicles (UFPLVs). Merocyanine 540 (MC540), as a photosensitizer, was loaded in the UFPLVs; doxorubicin hydrochloride (DOX), as an antitumor drug, was conjugated to the surfaces of UFPLVs by pH-sensitive hydrazone bonds. The newly developed MC540&DOX-UFPLVs had a nanosized structure with targeting ligand modification, so they had the potential to accumulate into tumor sites via a combination of passive and active targeting effects. An in vitro singlet oxygen test showed that the nanocarriers can generate cytotoxic singlet oxygen successfully under the irradiation of NIR light. In vitro DOX release profiles demonstrated that the nanocarriers can achieve a pH-triggered drug release. It has been demonstrated by a cellular uptake study that the nanocarriers can efficiently deliver drugs and photosensitizers into tumor cells. In vitro and in vivo combination treatments evidenced the high antitumor effects of MC540&DOX-UFPLVs under NIR light irradiation. These results suggest that the MC540&DOX-UFPLVs may be promising nanocarriers for tumor combination therapy applications.
authors.affiliation: School of Life Sciences, School of Materials Science and Engineering, Tianjin University, Tianjin 300072, PR China. jinchang@tju.edu.cn wanghj@tju.edu.cn.
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Life Sciences, School of Materials Science and Engineering, Tianjin University, Tianjin 300072, PR China. jinchang@tju.edu.cn wanghj@tju.edu.cn.
authors.forename: Weitao
authors.initials: W
authors.lastname: Yang
authors.affiliation: The second hospital of Tianjin Medical University, Tianjin 300211, PR China. lixiaodonglxd@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.affiliation: The second hospital of Tianjin Medical University, Tianjin 300211, PR China. lixiaodonglxd@163.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Life Sciences, School of Materials Science and Engineering, Tianjin University, Tianjin 300072, PR China. jinchang@tju.edu.cn wanghj@tju.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dou
authors.affiliation: School of Life Sciences, School of Materials Science and Engineering, Tianjin University, Tianjin 300072, PR China. jinchang@tju.edu.cn wanghj@tju.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Su
authors.affiliation: School of Life Sciences, School of Materials Science and Engineering, Tianjin University, Tianjin 300072, PR China. jinchang@tju.edu.cn wanghj@tju.edu.cn and Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chang
authors.affiliation: School of Life Sciences, School of Materials Science and Engineering, Tianjin University, Tianjin 300072, PR China. jinchang@tju.edu.cn wanghj@tju.edu.cn and Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, PR China.
authors.forename: Hanjie
authors.initials: H
authors.lastname: Wang
authors.affiliation: The second hospital of Tianjin Medical University, Tianjin 300211, PR China. lixiaodonglxd@163.com.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.affiliation: Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, PR China.
authors.forename: Bingbo
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007259:Infrared Rays; D053758:Nanoparticles / Q000737:chemistry*; D010778:Photochemotherapy / Q000295:instrumentation*; D017319:Photosensitizing Agents / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011744:Pyrimidinones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D017319:Photosensitizing Agents; D011108:Polymers; D011744:Pyrimidinones; C003954:merocyanine dye