Tumor-pH-Sensitive PLLA-Based Microsphere with Acid Cleavable Acetal Bonds on the Backbone for Efficient Localized Chemotherapy,Biomacromolecules

当前位置： X-MOL 学术 › Biomacromolecules › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Tumor-pH-Sensitive PLLA-Based Microsphere with Acid Cleavable Acetal Bonds on the Backbone for Efficient Localized Chemotherapy
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-06-08 00:00:00 , DOI: 10.1021/acs.biomac.8b00734
Junhua Li ₁ , Xuequan Zhang ₂ , Mingying Zhao ₂ , Lihuang Wu ₁ , Kui Luo ₃ , Yuji Pu ₁ , Bin He ₁

Affiliation

Nanoparticle- and microsphere-based drug delivery systems (DDSs) have attracted wide attention in cancer therapy; those DDSs that are responsive to tumor environment can selectively identify tumor and normal tissues and therefore have shown enhanced anticancer efficacy and alleviated systemic toxicity. Here, tumor-pH-sensitive polymeric microspheres, which are prepared by multiblock poly(l-lactide) with pH-sensitive acetal bonds in the backbone, are employed to efficiently load water-soluble anticancer drug doxorubicin hydrochloride (DOX·HCl, drug loading content: ∼10%). The pH-sensitive DOX-loaded hollow microspheres were in the size range 2–10 μm and exhibited acid-accelerated degradation of polymer matrix and drug release, and thereby efficient in vitro cancer cell inhibition. The microspheres were further intratumorally injected into breast-tumor-bearing mice, and the in vivo anticancer experiment showed that pH-sensitive DOX-loaded microsphere showed better antitumor efficiency and prolonged life-span than its counterpart that does not have pH-responsive property. Moreover, negligible organ toxicity, especially cardiotoxicity that generally exists in DOX-involved chemotherapy where DOX is administrated by intravenous injection, was observed for DOX-loaded microspheres. Hence, tumor-pH-sensitive polymeric microspheres have appeared to be a simple and efficient platform for delivering hydrophilic anticancer drug with excellent anticancer efficacy and low systemic toxicity.

中文翻译：

肿瘤pH敏感的基于PLLA的微球，在骨架上具有酸可裂解的缩醛键，可进行高效的局部化学治疗

基于纳米颗粒和微球的药物递送系统（DDS）在癌症治疗中引起了广泛关注。那些对肿瘤环境有反应的DDS可以选择性地识别肿瘤和正常组织，因此显示出增强的抗癌功效和减轻的全身毒性。在这里，通过对骨架中具有pH敏感的乙缩醛键的多嵌段聚（l-丙交酯）制备的对肿瘤pH敏感的聚合物微球可有效地负载水溶性抗癌药物盐酸阿霉素（DOX·HCl），药物负载含量：〜10％）。pH敏感的DOX负载的中空微球尺寸范围为2-10μm，并表现出酸加速的聚合物基质降解和药物释放，因此在体外有效癌细胞抑制作用。将微球进一步瘤内注射到荷瘤小鼠中，体内抗癌实验表明，与不具有pH响应特性的对应物相比，加载pH敏感的DOX的微球显示出更好的抗肿瘤效率和更长的寿命。此外，对于载有DOX的微球，观察到的器官毒性微不足道，特别是在通过DOX静脉注射给药的DOX涉及的化疗中通常存在的心脏毒性。因此，肿瘤pH敏感的聚合物微球似乎是一种简单有效的平台，可用于输送亲水性抗癌药物，具有出色的抗癌功效和低全身毒性。

更新日期：2018-06-08

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南