Self-quenchable biofunctional nanoparticles of heparin–folate-photosensitizer conjugates for photodynamic therapy
Self-quenchable biofunctional nanoparticles of heparin–folate-photosensitizer conjugates for photodynamic therapy
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DOI：
10.1016/j.carbpol.2011.05.011
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发表时间：
2011-08
影响因子：
11.2
通讯作者：
Li Li-Li;Byoung-chan Bae;T. Tran;Kwonhyeok Yoon;K. Na;K. Huh
中科院分区：
文献类型：
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作者：
Li Li-Li;Byoung-chan Bae;T. Tran;Kwonhyeok Yoon;K. Na;K. Huh
通过化学偶联肝素、疏水性光敏剂脱镁叶绿酸a（PhA）和靶向配体叶酸，合成了新型两亲性多糖/PS偶联物，研究了其在光动力学治疗（PDT）中的潜在应用。肝素-PhA（HP）和叶酸-肝素-PhA（FHP）缀合物的抗凝活性与肝素相比显著降低，从而潜在地减少出血性副作用。共轭物的临界自猝灭浓度随PhA含量的增加而降低。HP和FHP缀合物在水介质中通过自组装过程形成纳米颗粒，纳米颗粒尺寸为130- 170 nm，尺寸分布呈单峰模式。通过测量DMF和PBS中单线态氧的产生来评价HP和FHP纳米颗粒的光活性。纳米粒子在PBS中表现出自光猝灭效应，而在DMF中单线态氧的产生显著增加。HP和FHP纳米颗粒对HeLa细胞表现出明显的光毒性，并且在没有光处理的情况下具有最小的暗毒性。
Novel amphiphilic polysaccharide/PS conjugates synthesized by chemical conjugation of heparin with a hydrophobic photosensitizer (PS), pheophorbide a (PhA), and a targeting ligand, folate, were investigated for their potential application in photodynamic therapy (PDT). The anticoagulant activity of heparin-PhA (HP) and folate–heparin–PhA (FHP) conjugates was significantly decreased compared to that of heparin, thereby potentially reducing the hemorrhagic side effects. The critical self-quenching concentrations of the conjugates were decreased as the content of PhA rose. HP and FHP conjugates formed nano-sized particles in aqueous medium through a self-assembling process, and the nanoparticles were 130–170nm in size, with a unimodal pattern of size distribution. Photoactivity of HP and FHP nanoparticles was evaluated by measuring the generation of singlet oxygen in DMF and PBS. The nanoparticles displayed a self-photoquenching effect in PBS, while the generation of singlet oxygen dramatically increased in DMF. HP and FHP nanoparticles exhibited marked phototoxicity on HeLa cells and were minimally dark-toxic without light treatment.