Cell-killing potential of a water-soluble radical initiator.
Cell-killing potential of a water-soluble radical initiator.
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水溶性自由基引发剂的细胞杀伤潜力。
DOI：
10.1002/ijc.1424
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发表时间：
2001
影响因子：
6.4
通讯作者：
Langer,R
中科院分区：
文献类型：
--
作者：
Ameer,GA;Crumpler,ET;Langer,R
重氮化合物2，2 ′-偶氮双[2-（2-咪唑啉-2-基）丙烷]二盐酸盐（AIPC）是一种水溶性自由基引发剂，可在温和温度（37°-40 ° C）下活化。该化合物的潜在生物医学应用包括通过自由基聚合制备水凝胶（例如，细胞包封或药物递送）和癌细胞的热敏化以诱导局部细胞死亡。在这项研究中，我们评估了该化合物是否可以在37° C体外和活体肿瘤动物模型中诱导细胞死亡。采用磺基罗丹明B比色法测定细胞毒性，通过监测体外人胶质瘤细胞的生长抑制来定量。将AIPC包埋在纤维蛋白凝胶中，并暴露于培养物中的细胞，作为将化合物定位在控释环境中的潜在方式。通过定量细胞中caspase-3活性来评估细胞死亡的作用机制。体内研究包括在大鼠皮下生长的人类胶质瘤肿瘤，以研究肿瘤内注射AIPC的影响。AIPC也被皮下注射到正常组织中。0.2%和0.02%（在RPMI培养基中的w/v）的浓度分别显示93%和84%的细胞生长抑制。48小时后，使用凝胶包埋AIPC的细胞生长抑制与溶液中AIPC获得的细胞生长抑制相当（0.2% w/v时86%抑制）。暴露于AIPC导致半胱天冬酶活性显著增加（20分钟后高达163个单位），表明诱导凋亡是AIPC的可能作用机制。组织学照片显示，相对于正常组织，癌组织对AIPC的作用更敏感。© 2001 Wiley利斯公司
The diazo compound, 2,2′‐azobis [2‐(2‐imidazolin‐2‐yl) propane] dihydrochloride (AIPC), is a water‐soluble radical initiator that can be activated at mild temperatures (37°–40°C). Potential biomedical applications of this compound include the fabrication of hydrogels by radical polymerization (e.g., cell encapsulation or drug delivery) and the thermal sensitization of cancerous cells to induce localized cell death. In this study we evaluated whether this compound could induce cell death at 37°Cin vitroandin vivousing a tumor animal model. Cytotoxicity was quantitated with a sulfo‐rhodamine B colorimetric assay by monitoring growth inhibition of human glioma cellsin vitro. AIPC was entrapped in fibrin gel and exposed to cells in culture as a potential way to localize the compound in a controlled release environment. The mechanism of action for cell death was evaluated by quantitating caspase‐3 activity in cells.In vivostudies included human glioma tumors that were grown subcutaneously in rats to study the effect of intra‐tumor injections of AIPC. AIPC was also injected subcutaneously into normal tissue. Concentrations of 0.2% and 0.02% (w/v in RPMI medium) showed 93% and 84% inhibition of cell growthin vitro, respectively. Cell‐growth inhibition using gel‐entrapped AIPC was comparable to that obtained with AIPC in solution after 48 hr (86% inhibition at 0.2% w/v). Exposure to AIPC resulted in a significant increase of caspase activity (up to 163 units after 20 min), suggesting induced apoptosis as a possible mechanism of action of the AIPC. Histological pictures showed that, relative to normal tissue, cancerous tissue was more sensitive to the effects of AIPC. © 2001 Wiley‐Liss, Inc.