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首页> 外文期刊>Journal of Microencapsulation: Microcapsules Liposomes Nanoparticles Microcells Microspheres >Effect of alginate microencapsulation on the catalytic efficiency and in vitro enzyme-prodrug therapeutic efficacy of cytosine deaminase and of recombinant E. coli expressing cytosine deaminase
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Effect of alginate microencapsulation on the catalytic efficiency and in vitro enzyme-prodrug therapeutic efficacy of cytosine deaminase and of recombinant E. coli expressing cytosine deaminase

机译：海藻酸钠微囊化对胞嘧啶脱氨酶和表达胞嘧啶脱氨酶的重组大肠杆菌催化效率和体外酶前药治疗效果的影响

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摘要

Cytosine deaminase (CD) catalyses the enzymatic conversion of the non-toxic prodrug 5-fluorocytosine (5-FC) to the potent chemotherapeutic form, 5-fluorouracil (5-FU). Intratumoral delivery of CD localises chemotherapy dose while reducing systemic toxicity. Encapsulation in biocompatible microcapsules immunoisolates CD and protects it from degradation. We report on the effect of alginate encapsulation on the catalytic and functional activity of isolated CD and recombinant E. coli engineered to express CD (E. coli(CD)). Alginate microcapsules containing either CD or Escherichia coli(CD) were prepared using ionotropic gelation. Conversion of 5-FC to 5-FU was quantitated in unencapsulated and encapsulated CD/E. coli(CD) using spectrophotometry, with a slower rate of conversion observed following encapsulation. Both encapsulated CD/5-FC and E. coli(CD)/5-FC resulted in cell kill and reduced proliferation of 9L rat glioma cells, which was comparable to direct 5-FU treatment. Our results show that encapsulation preserves the therapeutic potential of CD and E. coli(CD) is equally effective for enzyme-prodrug therapy.
机译：胞嘧啶脱氨酶（CD）催化无毒前药5-氟胞嘧啶（5-FC）转化为有效的化学治疗形式5-氟尿嘧啶（5-FU）的酶促转化。 CD的肿瘤内递送可定位化疗剂量，同时降低全身毒性。封装在生物相容性微胶囊中可免疫分离CD，并保护CD免受降解。我们报告海藻酸盐封装对分离的CD和重组表达工程CD（E. coli（CD））的大肠杆菌的催化和功能活性的影响。使用离子凝胶法制备含有CD或大肠杆菌（CD）的藻酸盐微胶囊。在未封装和封装的CD / E中定量了5-FC向5-FU的转化。使用分光光度法测定大肠埃希菌（CD），并在封装后观察到较慢的转化率。封装的CD / 5-FC和大肠杆菌（CD）/ 5-FC均导致细胞杀伤并降低9L大鼠神经胶质瘤细胞的增殖，这与直接5-FU治疗相当。我们的结果表明，封装保留了CD的治疗潜力，而E. coli（CD）对于酶-前药治疗同样有效。

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