Fabrication of serum albumin-copper phthalocyanine nanoparticles for mitochondria-targeted phototherapy

doi:10.11949/0438-1157.20201078

Abstract

Abstract:

Copper phthalocyanine is a kind of dye with excellent photophysical properties and good photothermal stability, and it has a wide range of applications in the fields of printing and dyeing, solar cells, sensors and so on. Serum albumin, as the main transport protein in the blood, is often used for loading and transporting small molecules and drugs. In this work, LGS-CuPC-BSA nanoparticles (NPs) were constructed by self-assemble of bovine serum albumin (BSA) and copper phthalocyanine dyes (LGS-CuPc), which works as an integrated reagent for photodynamic and photothermal therapy. Under illumination at 671 nm (800 mW·cm^-2), the reactive oxygen species yield of LGS-CuPc-BSA NPs reached 23.3%, and the photothermal conversion efficiency was 36.8%. Compared with LGS-CuPc, LGS-CuPc-BSA nanoparticles showed low cytotoxicity, good biocompatibility and mitochondrial localization in tumor cells. LGS-CuPc-BSA nanoparticles significantly promoted cell apoptosis in vitro, realizing the combination therapy of photothermal and photodynamic therapy.

Key words: copper phthalocyanine, bovine serum albumin, photothermal therapy, photodynamic therapy, nanomaterials

摘要：

铜酞菁是一类具有优异光物理性质和良好光热稳定性的染料，在印染、太阳能电池、传感器等领域中应用广泛。血清白蛋白作为血液中主要的转运蛋白，常用于小分子和药物的负载和运输。通过牛血清白蛋白（BSA）和铜酞菁类染料（LGS-CuPc）的自组装，构建了LGS-CuPc-BSA纳米粒子（LGS-CuPc-BSA NPs），研究了其作为光动力和光热一体化试剂在光疗中的作用。在671 nm光照下（800 mW·cm^-2），LGS-CuPc-BSA NPs活性氧产率达到23.3%，光热转换效率为36.8%。与LGS-CuPc比较，LGS-CuPc-BSA NPs光动力和光热治疗效果明显提升，且表现出较低的细胞毒性、良好的生物相容性以及在肿瘤细胞线粒体的定位能力，实现对肿瘤细胞的有效杀伤。

关键词: 铜酞菁, 牛血清白蛋白, 光热治疗, 光动治疗, 纳米材料

CLC Number:

TQ 613.5

YU Fuqiang, DU Jianjun, LU Yang, MA He, FAN Jiangli, SUN Wen, LONG Saran, PENG Xiaojun. Fabrication of serum albumin-copper phthalocyanine nanoparticles for mitochondria-targeted phototherapy[J]. CIESC Journal, 2021, 72(1): 597-608.

于富强, 杜健军, 路杨, 马贺, 樊江莉, 孙文, 龙飒然, 彭孝军. 血清白蛋白-铜酞菁纳米粒子用于线粒体靶向光疗[J]. 化工学报, 2021, 72(1): 597-608.

Figures/Tables 17

Fig.1 Schematic illustration of preparation of LGS-CuPc-BSA NPs for mitochondrial targeted phototherapy

Fig.2 UV–vis absorption spectra of LGS-CuPc and LGS-CuPc-BSA NPs (a) and TEM image of LGS-CuPc-BSA NPs (b)

Fig.3 Singlet-oxygen generation of MB(a), LGS-CuPc(b), LGS-CuPc-BSA NPs (c) in DMF with DPBF, and the linear relationship between time and absorption of MB, LGS- CuPc, and LGS-CuPc-BSA NPs (d)

Fig.4 Photothermal heating curves for the change of temperature with time in different concentrations (20, 30, and 40 μmol·L-1) of LGS-CuPc (a), LGS-CuPc-BSA NPs irradiated by 671 nm laser (800 mW·cm-2) (b). The temperature variations of LGS-CuPc-BSA NPs for 5 cycles (20 min per cycle) (c). Calculation of τ value (d)

Fig.5 Cell viabilities after treatments with different concentrations of LGS-CuPc-BSA NPs (a) and LGS-CuPc (b) with and without 671 nm (800 mW·cm-2) laser irradiation for 10 min

Fig.6 Confocal images of co-stained MCF-7 cells with AM and PI in the presence of LGS-CuPc-BSA NPs and LGS-CuPc

Fig.7 ROS generation in MCF-7 cells

Fig.8 Confocal fluorescence images of Hoechst33342 and LGS-CuPc-BSA NPs in MCF-7 cells

Fig.9 Co-localization imaging of LGS-CuPc-BSA NPs and Mito-Tracker Green in MCF-7 cells

Fig.A1 Structure of LGS-CuPc, C.I.Direct Blue86

Fig.A2 TEM image of BSA

Fig.A3 Size distributions of LGS-CuPc-BSA NPs in PBS

Fig.A4 The ζ potentials of LGS-CuPc-BSA NPs in aqueous solution

Fig.A5 Size and PDI of LGS-CuPc-BSA NPs in PBS

Fig.A6 UV-vis absorption spectra of LGS-CuPc at different concentration

Fig.A7 The linear relationship between LGS-CuPc concentration and absorption intensity at 671 nm

Fig.A8 In vivo NIR fluorescencent images

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