Key Laboratory of Advanced Technologies of Materials, Ministry of Education of China, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, PR China.
Eur J Pharm Biopharm. 2012 Nov;82(3):545-53. doi: 10.1016/j.ejpb.2012.08.012. Epub 2012 Sep 17.
The acidosis of tumor microenvironments is one of the universal phenomena of solid tumors, and the increased acidity may be in fact essential intermediates in the progression of tumor growth and several lethal phenotypic traits of tumors, such as invasion and metastasis. Acid-labile polymers PBELA with incorporating acetal groups into biodegradable backbone of poly(d,l-lactide)-poly(ethylene glycol) (PELA) were utilized to load hydroxycamptothecin (HCPT) into electrospun fibers for intratumoral chemotherapy. Compared with that under a simulated physiological condition of pH 7.4, the incubation of PBELA fibers in acidic media resulted in larger mass loss and molecular weight reduction of fiber matrices and enhanced HCPT release from fibers. In vitro cytotoxicity assay of HCPT-loaded PBELA fibers indicated 6-fold higher inhibitory activity against HepG2 cells after incubation in pH 6.8 media than that of pH 7.4, while there was no significant difference for free HCPT and HCPT-loaded PELA fibers. The tumor growth, tumor cell apoptosis, and animal survival rate after intratumoral implantation of HCPT-loaded PBELA fibers indicated a superior in vivo antitumor activity and fewer side effects than other treatment. Therefore, acid-labile electrospun fibers may be promising implants for localized therapy of inoperable tumors and for prevention of post-surgical tumor recurrence.
肿瘤微环境的酸中毒是实体瘤的普遍现象之一，酸度的增加实际上可能是肿瘤生长和侵袭、转移等几种致命肿瘤表型特征的重要中间产物。将缩醛基团引入可生物降解的聚（D，L-丙交酯）-聚（乙二醇）（PELA）主链中的酸不稳定聚合物 PBELA 被用于将羟基喜树碱（HCPT）负载到电纺纤维中进行肿瘤内化疗。与在 pH 值为 7.4 的模拟生理条件下相比，在酸性介质中孵育 PBELA 纤维会导致纤维基质的质量损失和分子量降低更大，并增强 HCPT 从纤维中的释放。在 pH 值为 6.8 的介质中孵育后，负载 HCPT 的 PBELA 纤维对 HepG2 细胞的体外细胞毒性测定显示出 6 倍的抑制活性，而 pH 值为 7.4 时则没有显著差异，对于游离 HCPT 和负载 HCPT 的 PELA 纤维也是如此。荷瘤小鼠瘤内植入负载 HCPT 的 PBELA 纤维后的肿瘤生长、肿瘤细胞凋亡和动物存活率表明，与其他治疗方法相比，其具有更好的体内抗肿瘤活性和更少的副作用。因此，酸不稳定的电纺纤维可能是用于不可切除肿瘤的局部治疗和预防手术后肿瘤复发的有前途的植入物。
