基于三苯基膦的线粒体靶向聚乳酸纳米载药系统的制备及其对 7-羟基香豆素的抗肿瘤活性

Preparation and antitumor activity of triphenylphosphine-based mitochondrial targeting polylactic acid nanoparticles loaded with 7-hydroxyl coumarin.

机构信息

Department of Pharmaceutics, School of Pharmacy, Hubei University of Science and Technology, Xianning, China.

Hubei Key Laboratory of Diabetes and Angiopathy, Hubei University of Science and Technology, Xianning, China.

出版信息

J Biomater Appl. 2022 Jan;36(6):1064-1075. doi: 10.1177/08853282211037030. Epub 2021 Aug 1.

DOI:10.1177/08853282211037030

PMID:34338057

Abstract

Due to the low bioavailability and severe toxic side effects caused by the lack of selectivity of traditional chemotherapy drugs, the targeted delivery of chemotherapy drugs has become the key to tumor treatment. The activity and transmembrane potential of mitochondria in cancer cells were significantly higher than that of normal cells, making them a potential target for chemotherapeutic drug delivery. In this study, triphenylphosphine (TPP) based mitochondria targeting polylactic acid (PLLA) nanoparticles (TPP-PLLA NPs) were synthesized to improve the delivery efficiency of anticancer drugs. The carrier material was characterized by H NMR and FT-IR and 7-hydroxyl coumarin (7-HC) was successfully loaded into TPP-PLLA to form 7-HC/TPP-PLLA NPs. Further studies showed that TPP-PLLA NPs were primarily accumulated in the mitochondrial and 7-HC/TPP-PLLA NPs had higher antitumor activity. Taken together, our results indicated that TPP-PLLA NPs could be a promising mitochondria-targeted drug delivery system for cancer therapy.

摘要

由于传统化疗药物缺乏选择性而导致的生物利用度低和严重的毒副作用，化疗药物的靶向递送已成为肿瘤治疗的关键。癌细胞中线粒体的活性和跨膜电位明显高于正常细胞，使其成为化疗药物递送的潜在靶点。在本研究中，合成了基于三苯基膦（TPP）的线粒体靶向聚乳酸（PLLA）纳米粒子（TPP-PLLA NPs），以提高抗癌药物的递送效率。载体材料通过 H NMR 和 FT-IR 进行了表征，并成功地将 7-羟基香豆素（7-HC）载入 TPP-PLLA 中，形成 7-HC/TPP-PLLA NPs。进一步的研究表明，TPP-PLLA NPs 主要在线粒体中积累，而 7-HC/TPP-PLLA NPs 具有更高的抗肿瘤活性。综上所述，我们的研究结果表明，TPP-PLLA NPs 可能是一种有前途的用于癌症治疗的线粒体靶向药物递送系统。