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基于上转换纳米材料发光和透明质酸特异性的新型光敏剂的构建
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摘要
光动力治疗(photodynamic therapy,PDT),相比于化学疗法和放射性疗法而言,属于微创性治疗手段。近几十年,PDT已经迅速发展成为化疗或放疗的有效替代手段,应用在许多包括癌症在内的疾病的治疗中~([1])。传统的PDT中,激发光敏剂分子的光源多为对人体组织穿透力较弱的可见光或紫外光,从而限制了PDT对更深层组织癌细胞的杀伤作用。为了弥补以上传统PDT的不足,许多研究中利用稀土掺杂的上转换纳米材料(upconversion nanoparticles,UCNPs)来作为光敏剂分子的载体~([2-4])。UCNPs可以被穿透能力强近红外光(near-infrared,NIR)激发而上转换出的可见或紫外光,继而也作为能量供体激发负载其上的光敏剂分子,实现对癌细胞的杀伤作用。本实验利用UCNPs@mSiO_2作为载体,将具有特异性识别癌细胞表面CD44蛋白的透明质酸(HA)分子~([5,6])嫁接到表面,一方面,赋予组合体对癌细胞的特异性识别功能;另一方面,利用HA封堵介孔硅表面孔隙,防止光敏剂分子的泄漏,从而构建一种强穿透力和高靶向的新型光敏剂。合成之后在肿瘤细胞和荷瘤小鼠中对新型光敏剂进行了初步的药效分析。
Photodynamic therapy(PDT) is known as minimally invasive therapy compared with chemotherapy and radiotherapy. In the past few decades, photodynamic therapy(PDT) has emerged as alternative treatment approach to chemotherapy and radiotherapy to treat various diseases including cancer. In traditional PDT, most PS molecules currently applied in PDT are excited by visible or even UV light, which exhibit rather poor penetration depth in biological tissues, thus limitting the application of PDT in the treatment of large or internal tumors. Many research reported a new approach to deliver light into deeper tissues for PDT treatment is using NIR-excitable upconversion nanoparticles(UCNPs) as an photosensitizer carrier. UCNPs have been considered as an energy donor, which emit high energy UV or visible photons under excitation by the NIR light, to excit photosensitizer loaded to kill cancer cell. This paper represent a solution, hyaluronic acid(HA),which have been reported to increase drug/cargo accumulation specically in CD44 over-expressing cancer cells,have been connected on the surface of UNCPs@mSiO_2 by covalent bonds. UNCPs@mSiO_2@HA are endowed with targeting to tumer cell,and hyaluronic acid coated could prevent photosensitizers leakage from the mesoporous. Eventually,we fabricate a new photosensitizers complex which have deep penetration depth and specific recognition.Then The success of using UCNP-PS nanocomplexes for in vitro PDT cancer cell killing under NIR light thus encourages further investigations of this approach for in vivo cancer treatment, which will be discussed in the following section.
引文
[1]Moan,J.;Peng,Q.Anticancer Res.2002,23;3591.
    [2]Qian,HS.;Guo,HC.;Ho,PCL.;Mahendran,R,et al.;Small.2009,5;2285.
    [3]Lim,ME.;Lee,Y-l.;Zhang,Y.;Chu,JJH.Biomaterials.2012,33;1912.
    [4]Zhao,Z.;Han,Y.;Lin,C.;Hu,D,et al.;Chem Asian J.2012,7;830.
    [5]Platt,VM.;Szoka Jr,FC.Mol Pharm.2008,5;474.
    [6]Toole,BP.Nat Rev Cancer.2004,4;528.

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