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基于双波段发光镧系纳米粒子的多功能成像与治疗平台用于抑制肿瘤转移

A Versatile Imaging and Therapeutic Platform Based on Dual-Band Luminescent Lanthanide Nanoparticles toward Tumor Metastasis Inhibition.

作者信息

Li Yang, Tang Jinglong, Pan Dong-Xu, Sun Ling-Dong, Chen Chunying, Liu Ying, Wang Ye-Fu, Shi Shuo, Yan Chun-Hua

机构信息

Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Rare Earth Materials Chemistry and Applications, PKU-HKU Joint Laboratory in Rare Earth Materials and Bioinorganic Chemistry, College of Chemistry and Molecular Engineering, Peking University , Beijing 100871, China.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China , Beijing 100190, China.

出版信息

ACS Nano. 2016 Feb 23;10(2):2766-73. doi: 10.1021/acsnano.5b07873. Epub 2016 Jan 26.

Abstract

Upconversion (UC) luminescent lanthanide nanoparticles (LNPs) are expected to play an important role in imaging and photodynamic therapy (PDT) in vitro and in vivo. However, with the absorption of UC emissions by photosensitizers (PSs) to generate singlet oxygen ((1)O2) for PDT, the imaging signals from LNPs are significantly weakened. It is important to activate another imaging route to track the location of the LNPs during PDT process. In this work, Nd(3+)-sensitized LNPs with dual-band visible and near-infrared (NIR) emissions under single 808 nm excitation were reported to address this issue. The UC emissions in green could trigger covalently linked rose bengal (RB) molecules for efficient PDT, and NIR emissions deriving from Yb(3+) and magnetic resonance imaging (MRI) were used for imaging simultaneously. Notably, the designed therapeutic platform could further effectively avoid the overheating effect induced by the laser irradiation, due to the minimized absorption of biological media at around 808 nm. TdT-mediated dUTP nick end labeling (TUNEL) assay showed serious cell apoptosis in the tumor after PDT for 2 weeks, leading to an effective tumor inhibition rate of 67%. Benefit from the PDT, the tumor growth-induced liver and spleen burdens were largely attenuated, and the liver injury was also alleviated. More importantly, pulmonary and hepatic tumor metastases were significantly reduced after PDT. The Nd(3+)-sensitized LNPs provide a multifunctional nanoplatform for NIR light-assisted PDT with minimized heating effect and an effective inhibition of tumor growth and metastasis.

摘要

上转换(UC)发光镧系纳米粒子(LNPs)有望在体外和体内成像及光动力疗法(PDT)中发挥重要作用。然而,由于光敏剂(PSs)吸收UC发射光以产生用于PDT的单线态氧(¹O₂),来自LNPs的成像信号会显著减弱。激活另一条成像途径以在PDT过程中追踪LNPs的位置很重要。在这项工作中,报道了在单一808 nm激发下具有双波段可见光和近红外(NIR)发射的Nd(3+)敏化LNPs来解决这个问题。绿色的UC发射光可触发共价连接的孟加拉玫瑰红(RB)分子以实现高效PDT,同时源自Yb(3+)的近红外发射和磁共振成像(MRI)用于成像。值得注意的是,由于生物介质在808 nm左右的吸收最小化,所设计的治疗平台可进一步有效避免激光照射引起的过热效应。TdT介导的dUTP缺口末端标记(TUNEL)分析显示,PDT治疗2周后肿瘤中出现严重的细胞凋亡,导致有效的肿瘤抑制率为67%。得益于PDT,肿瘤生长引起的肝脏和脾脏负担大大减轻,肝损伤也得到缓解。更重要的是,PDT后肺和肝肿瘤转移显著减少。Nd(3+)敏化的LNPs为近红外光辅助PDT提供了一个多功能纳米平台,具有最小化的热效应,并能有效抑制肿瘤生长和转移。

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