Targeting-Triggered Porphysome Nanostructure Disruption for Activatable Photodynamic Therapy
Targeting-Triggered Porphysome Nanostructure Disruption for Activatable Photodynamic Therapy
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DOI：
10.1002/adhm.201300651
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发表时间：
2014-08-01
影响因子：
10
通讯作者：
Zheng, Gang
中科院分区：
文献类型：
--
作者：
Jin, Cheng S.;Cui, Liyang;Zheng, Gang
光动力学疗法（PDT）和光热疗法（PTT）具有传统疗法的优点，并通过局部激光照射实现额外的治疗选择性。与通过热坏死消融靶组织的PTT相比，PDT通过单线态氧诱导靶细胞死亡而不损伤下层结缔组织，从而保留其生物学功能。可活化的光敏剂通过疾病相关的活化机制提供额外水平的治疗选择性。在这项研究中，叶酸偶联卟啉囊泡作为靶向触发可激活的PDT纳米级信标。卟啉囊泡是目前报道的最稳定、最有效的卟啉释放系统，但其纳米结构将单线态氧的产生机制转化为热烧蚀机制。通过叶酸受体介导的内吞作用，叶酸-卟啉小体被迅速内化到细胞中，并导致纳米结构的有效破坏，从而切换回用于有效PDT的密集堆积的卟啉的光动力活性。在体外和体内研究中，叶酸-卟啉体可以实现叶酸受体选择性PDT功效，这证明了靶向触发的卟啉体纳米结构的PDT活化对于高选择性肿瘤消融的稳健性。卟啉囊泡的剂型可以用其他靶向配体进行修饰，作为可激活的光敏剂，用于未来的个性化治疗。
Photodynamic therapy (PDT) and photothermal therapy (PTT) possess advantages over the conventional therapies with additional treatment selectivity achieved with local laser irradiation. Comparing to PTT that ablates target tissue via thermal necrosis, PDT induces target cell death via singlet oxygen without damaging the underling connective tissue, thus preserving its biological function. Activatable photosensitizers provide an additional level of treatment selectivity via the disease-associated activation mechanism. In this study, folate-conjugated porphysomes are introduced as targeting-triggered activatable nano-sized beacons for PDT. Porphysomes are reported previously as the most stable and efficient delivery system of porphyrin, but their nanostructure converts the singlet oxygen generation mechanism to thermal ablation mechanism. By folate-receptor-mediated endocytosis, folate-porphysomes are internalized into cells rapidly and resulted in efficient disruption of nanostructures, thus switching back on the photodynamic activity of the densely packed porphyrins for effective PDT. In both in vitro and in vivo studies, folate-porphysomes can achieve folate receptor-selective PDT efficacy, which proves the robustness of targeting-triggered PDT activation of porphysome nanostructure for highly selective tumor ablation. The formulation of porphysomes can be modified with other targeting ligands as activatable photosensitizers for personalized treatment in future.