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一种基于硫化铜和氯e6的用于光热和光动力联合治疗的高效双负载多功能纳米载体。

An efficient dual-loaded multifunctional nanocarrier for combined photothermal and photodynamic therapy based on copper sulfide and chlorin e6.

作者信息

Tan Xiaoxiao, Pang Xiaojuan, Lei Mingzhu, Ma Man, Guo Fang, Wang Jinping, Yu Meng, Tan Fengping, Li Nan

机构信息

Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, PR China.

Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, PR China.

出版信息

Int J Pharm. 2016 Apr 30;503(1-2):220-8. doi: 10.1016/j.ijpharm.2016.03.019. Epub 2016 Mar 14.

Abstract

The therapeutic effectiveness of photodynamic therapy (PDT) was hampered by the poor water solubility and instability in physiological conditions of the photosensitizers. Here, we designed folate conjugated thermosensitive liposomes (TSL) as the nanocarrier to improve the solubility, stability and biocompatibility of photosensitizer Chlorin e6 (Ce6). Based on the photothermal effect, we combined copper sulfide (CuS) as the photothermal agent to realize heat-triggered Ce6 release as well as synergistic effect of photothermal and photodynamic therapy. In vitro MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay showed that Ce6-CuS-TSL had low dark toxicity, while performed excellent phototoxicity under the combined 660 and 808 nm laser irradiation compared to any single laser irradiation alone. Moreover, in vivo combination therapy study revealed that Ce6-CuS-TSL inhibited tumor growth to a great extent without evident side effect under the laser irradiation. All detailed evidence demonstrated a considerable potential of Ce6-CuS-TSL for synergistic cancer treatment.

摘要

光动力疗法(PDT)的治疗效果受到光敏剂在生理条件下水溶性差和稳定性低的限制。在此,我们设计了叶酸偶联热敏脂质体(TSL)作为纳米载体,以提高光敏剂叶绿素e6(Ce6)的溶解度、稳定性和生物相容性。基于光热效应,我们将硫化铜(CuS)作为光热剂,以实现热触发的Ce6释放以及光热和光动力疗法的协同效应。体外MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐)试验表明,Ce6-CuS-TSL具有低暗毒性,而与任何单一激光照射相比,在660和808 nm激光联合照射下表现出优异的光毒性。此外,体内联合治疗研究表明,在激光照射下,Ce6-CuS-TSL在很大程度上抑制了肿瘤生长,且无明显副作用。所有详细证据表明Ce6-CuS-TSL在协同癌症治疗方面具有巨大潜力。

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