In Vivo Targeted Deep-Tissue Photodynamic Therapy Based on Near-Infrared Light Triggered Upconversion Nanoconstruct
In Vivo Targeted Deep-Tissue Photodynamic Therapy Based on Near-Infrared Light Triggered Upconversion Nanoconstruct
复制标题
基于近红外光触发上转换纳米结构的体内靶向深部组织光动力治疗
DOI：
10.1021/nn304872n
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发表时间：
2013-01-01
期刊：
影响因子：
17.1
通讯作者：
Gu, Yueqing
中科院分区：
文献类型：
--
作者：
Cui, Sisi;Yin, Deyan;Gu, Yueqing
当前光动力疗法（PDT）的两个主要挑战是激发光的有限组织穿透和光敏剂（PS）的差的肿瘤选择性。为了解决这些问题，我们开发了一种多功能纳米结构，包括将近红外（NIR）光转换为可见光的上转换纳米颗粒（UCNPs）和光敏剂酞菁锌（II）（ZnPc）。将叶酸修饰的两亲性壳聚糖（FASOC）包覆在UCNPs表面，使ZnPc与UCNPs紧密锚在一起，从而促进UCNPs与ZnPc之间的共振能量转移。共聚焦显微镜和近红外小动物成像证明了纳米结构对过表达叶酸受体的癌细胞的增强的肿瘤选择性。活性氧（ROS）的产生在癌细胞下1厘米的组织是更高的UCNPs激发与980 nm的光比660 nm的照射。体内PDT治疗深部肿瘤的实验表明，基于纳米结构的近红外光触发PDT具有显著的治疗效果，肿瘤抑制率高达50%，而传统的可见光激活PDT的肿瘤抑制率明显降低18%。这些结果表明，多功能纳米构建体是用于深层肿瘤治疗的有前景的PDT试剂，并展示了用于增强PDT功效的新范例。
Two major challenges of current photodynamic therapy (PDT) are the limited tissue penetration of excitation light and poor tumor-selectivity of the photosensitizer (PS). To address these issues, we developed a multifunctional nanoconstruct consisting of upconverslon nanoparticles (UCNPs) that transform near-Infrared (NIR) light to visible light and a photosensitizer zinc(II) phthalocyanine (ZnPc). Folate-modified amphiphilic chitosan (FASOC) was coated on the surface of UCNPs to anchor the ZnPc close to the UCNPs, thereby facilitating resonance energy transfer from UCNPs to ZnPc. Confocal microscopy and NIR small animal imaging demonstrated the enhanced tumor-selectivity of the nanoconstructs to cancer cells that overexpressed folate receptor. Reactive oxygen species (ROS) generation in cancer cells under a 1-cm tissue was higher upon excitation of UCNPs with the 980 nm light than that with 660 nm irradiation. In vivo PDT treatments for deep-seated tumors demonstrated that NIR light-triggered PDT based on the nanoconstructs possessed remarkable therapeutic efficacy with tumor inhibition ratio up to 50% compared with conventional visible light-activated PDT with a noticeable reduced tumor inhibition ratio of 18%. These results indicate that the multifunctional nanoconstruct Is a promising PDT agent for deep-seated tumor treatment and demonstrate a new paradigm for enhancing PDT efficacy.