NUS Graduate School for Integrative Sciences & Engineering (NGS) , Singapore 117456.
ACS Nano. 2015 Jan 27;9(1):191-205. doi: 10.1021/nn503450t. Epub 2015 Jan 7.
Because of the limited penetration depth of visible light that generally excites most of the available photosensitizers (PSs), conventional photodynamic therapy (PDT) is limited to the treatment of superficial and flat lesions. Recently, the application of deep penetrating near-infrared (NIR) light excitable upconversion nanoparticles (UCNs) in conjunction with PDT has shown to have clear potential in the treatment of solid tumors due to its ability to penetrate thick tissue. However, various constructs developed so far have certain limitations such as poor or unstable PS loading, reducing their therapeutic efficacy and limiting their application to solution or cell-based studies. In this work, we present a method to fabricate uniform core-shell structured nanoconstruct with a thin layer of photocatalyst or PS-titanium dioxide (TiO2) stably coated on individual UCN core. Our design allows controllable and highly reproducible PS loading, preventing any leakage of PS compared to previously developed nanoconstructs, thus ensuring repeatable PDT results. Further surface modification of the developed nanoconstructs with polyethylene glycol (PEG) rendered them biocompatible, demonstrating good therapeutic efficacy both in vitro and in vivo.
由于可见光的穿透深度有限,通常只能激发大部分可用的光敏剂 (PS),传统的光动力疗法 (PDT) 仅限于治疗浅表和扁平的病变。最近,与 PDT 结合使用的深穿透近红外 (NIR) 光激发上转换纳米粒子 (UCN) 的应用因其能够穿透厚组织而在治疗实体瘤方面显示出明显的潜力。然而,迄今为止开发的各种构建体具有一定的局限性,例如 PS 负载不良或不稳定,从而降低了它们的治疗效果,并限制了它们在溶液或基于细胞的研究中的应用。在这项工作中,我们提出了一种制造具有均匀核壳结构纳米结构的方法,其中在单个 UCN 核上稳定地涂覆有薄的光催化剂或 PS-二氧化钛 (TiO2)。我们的设计允许可控且高度可重复的 PS 负载,与以前开发的纳米结构相比,防止 PS 的任何泄漏,从而确保可重复的 PDT 结果。通过进一步用聚乙二醇 (PEG) 对开发的纳米结构进行表面修饰,使其具有生物相容性,在体外和体内均表现出良好的治疗效果。