Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy.
Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy.
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DOI：
10.2147/ijn.s89474
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发表时间：
2015
影响因子：
8
通讯作者：
Rao NM
中科院分区：
文献类型：
--
作者：
Narsireddy A;Vijayashree K;Adimoolam MG;Manorama SV;Rao NM
光动力疗法面临的挑战包括开发高效的近红外光敏剂((5，10，15，20-tetrakis(4-hydroxyphenyl)-21H，23H-porphine[PS])和向肿瘤组织靶向输送PS。本研究合成了一种用于靶向PDT的双功能树枝状大分子。为了靶向，将聚酰胺胺树枝状大分子(G4)与PS和NTA基团偶联。利用His标签在大肠杆菌中表达了人表皮生长因子2的特异性多肽，并与树状大分子上的NTA基团特异性结合。对反应条件进行了优化，得到了PS和NTA的比例分别为50%和15%的树状大分子。用核磁共振、基质辅助激光解吸/电离、吸光度和荧光光谱对树枝状大分子进行了表征。利用PS荧光，通过共聚焦显微镜和荧光激活的细胞分选证实细胞摄取这些颗粒。在HER2阳性细胞SK-OV-3中，PS-树枝状大分子在PDT介导的细胞死亡分析中比游离PS更有效。在HER2阴性细胞系MCF-7中没有类似的作用。与游离PS相比，PS-树枝状大分子在异种动物肿瘤模型中显示出显著的肿瘤抑制作用。PS与树状大分子和靶向剂的偶联增强了PS的光动力治疗效果。
Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.