Pegylated Composite Nanoparticles Containing Upconverting Phosphors and meso-Tetraphenyl porphine (TPP) for Photodynamic Therapy
Pegylated Composite Nanoparticles Containing Upconverting Phosphors and meso-Tetraphenyl porphine (TPP) for Photodynamic Therapy
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DOI：
10.1002/adfm.201002516
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发表时间：
2011-07-08
影响因子：
19
通讯作者：
Prud'homme, Robert K.
中科院分区：
文献类型：
--
作者：
Shan, Jingning;Budijono, Stephanie J.;Prud'homme, Robert K.
上转换纳米磷光体（UCNP）用于光动力疗法（PDT）的利用由于其将深穿透近红外（NIR）光（即，978 nm）至可见光。先前尝试将UCNPs与光敏剂共定位的尝试遭受低光敏剂负载和纳米颗粒聚集的问题。在此，提出了一种新型复合纳米颗粒制剂的制备，该制剂包含100 nm β-NaYF 4：Yb 3+，Er 3 + UCNP和内消旋四苯基卟啉（TPP）光敏剂，通过生物相容性聚（乙二醇-嵌段-（DL）乳酸）嵌段共聚物（PEG-b-PLA）稳定。通过快速纳米沉淀（FNP）工艺实现相对于UCNP晶体10重量%的光敏剂负载。复合纳米颗粒表面上的空间稳定PEG层防止纳米颗粒聚集并确保纳米颗粒在水、PBS缓冲液和含有血清蛋白的培养基中的稳定性，从而产生适合于体内应用的纳米颗粒。基于利用HeLa宫颈癌细胞系的体外研究，复合纳米颗粒显示出在NIR激发下的低暗毒性和有效的癌细胞杀伤活性。用134 W cm（-2）的978 nm光照射45 min，导致75%的HeLa细胞死亡。这是第一次定量的细胞杀伤能力的UCNP/TPP复合纳米粒子配制的光动力疗法。
The utilization of upconverting nanophosphors (UCNP) for photodynamic therapy (PDT) has gained significant interests due to its ability to convert deep-penetrating near-infra red (NIR) light (i.e., 978 nm) to visible light. Previous attempts to co-localize UCNPs with photosensitizers suffer from low photosensitizer loading and problems with nanoparticle aggregation. Here, the preparation of a novel composite nanoparticle formulation comprising 100 nm beta-NaYF4 : Yb3+, Er3+ UCNPs, and meso-tetraphenyl porphine (TPP) photosensitizer, stabilized by biocompatible poly(ethylene glycol-block-(DL)lactic acid) block copolymers (PEG-b-PLA) is presented. A photosensitizer loading of 10 wt% with respect to UCNP crystal was achieved via the Flash NanoPrecipitation (FNP) process. A sterically stabilizing PEG layer on the composite nanoparticle surface prevents nanoparticle aggregation and ensures nanoparticle stability in water, PBS buffer, and culture medium containing serum proteins, resulting in nanoparticle suitable for in vivo applications. Based on in vitro studies utilizing HeLa cervical cancer cell lines, the composite nanoparticles are shown to exhibit low dark toxicity and efficient cancer cell-killing activity upon NIR excitation. Exposure with 134 W cm(-2) of 978 nm light for 45 min resulted in 75% HeLa cell death. This is the first quantification of the cell-killing capabilities of the UCNP/TPP composite nanoparticles formulated for photodynamic therapy.