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Oligo(p-phenylenevinylene) Derivative-Incorporated and Enzyme-Responsive Hybrid Hydrogel for Tumor Cell-Specific Imaging and Activatable Photodynamic Therapy
ACS Biomaterials Science & Engineering ( IF 5.8 ) Pub Date : 2017-09-13 00:00:00 , DOI: 10.1021/acsbiomaterials.7b00610
Meng Li 1 , Ping He 1 , Shengliang Li 1 , Xiaoyu Wang 1 , Libing Liu 1 , Fengting Lv 1 , Shu Wang 1
Affiliation  

Tumor-cell targeted and subcellular organelles-specific photosensitizer is imperative for high-efficiency photodynamic therapy (PDT). Herein, we designed and synthesized a new conjugated oligomer, oligo(p-phenylenevinylene-co-benzothiazole) (OPVBT), which could be used as photosensitizer to generate reactive oxygen species (ROS) upon light illumination. Advantageously, OPVBT was found to specifically accumulate in mitochondria, which is beneficial for effective subcellular organelles-targeted PDT. A biocompatible and biodegradable hydrogel was constructed based on Michael-type addition between cysteine-terminated matrix metalloproteinase (MMP)-cleavable oligopeptides and 4-arm vinyl sulfone-terminated poly(ethylene glycol) (PEG-VS). By functionalizing hydrogel with OPVBT and cell adhesion peptide motif RGD, cell attachment and spreading on the hydrogel were easily realized. More importantly, because of the MMP-sensitivity of the hydrogel, tumor cells could be specifically lighted up by OPVBT liberated from the hydrogel and the growth of tumor cells are further restrained by ROS generated from OPVBT upon light illumination. The hybrid hydrogel provides a new platform for tumor-specific imaging and killing, which shows good potential for constructing targeted PDT system with reduced side effects.

中文翻译:

Oligo(对苯撑乙烯撑)衍生物结合和酶促反应的混合水凝胶用于肿瘤细胞特异性成像和可激活的光动力疗法。

肿瘤细胞靶向和亚细胞器特异性光敏剂对于高效光动力疗法(PDT)至关重要。在此,我们设计并合成了新的共轭低聚物,低聚(p -phenylenevinylene--苯并噻唑(OPVBT),可用作光敏剂,在光照下可产生活性氧(ROS)。有利地,发现OPVBT特异性地积聚在线粒体中,这对于有效的靶向亚细胞器的PDT是有益的。基于在半胱氨酸终止的基质金属蛋白酶(MMP)可切割的寡肽和4-臂乙烯基砜终止的聚乙二醇(PEG-VS)之间的迈克尔型加成,构建了生物相容性和可生物降解的水凝胶。通过用OPVBT和细胞粘附肽基序RGD对水凝胶进行功能化,可以轻松实现细胞附着和在水凝胶上的扩散。更重要的是,由于水凝胶对MMP敏感,从水凝胶中释放出来的OPVBT可以特异性地点亮肿瘤细胞,而光照后OPVBT产生的ROS可以进一步抑制肿瘤细胞的生长。混合水凝胶为肿瘤特异性成像和杀伤提供了新的平台,显示出构建具有降低副作用的靶向PDT系统的良好潜力。
更新日期:2017-09-13
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