Dynamic core crosslinked camptothecin prodrug micelles with reduction sensitivity and boronic acid-mediated enhanced endocytosis: An intelligent tumor-targeted delivery nanoplatform
| Autor: | Shulei Zhu, Yanyun Xu, Wei Lu, Jiahui Yu, Tiandong Chen, Yushu Huang, Wu Yanqian, Xiongwen Zhang, Yi Xiao, Wanli Zhang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Polymers
Mice Nude Pharmaceutical Science Antineoplastic Agents 02 engineering and technology Endocytosis 030226 pharmacology & pharmacy Micelle Polyethylene Glycols Mice 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems 0302 clinical medicine In vivo Cell Line Tumor PEG ratio medicine Animals Humans Prodrugs Phenylboronic acid Micelles Drug Carriers Mice Inbred BALB C Hep G2 Cells Prodrug 021001 nanoscience & nanotechnology Boronic Acids Drug Liberation Polyglutamic Acid chemistry Drug delivery Biophysics Nanoparticles Camptothecin Female 0210 nano-technology medicine.drug |
| Zdroj: | International Journal of Pharmaceutics. 580:119250 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2020.119250 |
| Popis: | The physicochemical properties of camptothecin (CPT) limit its clinical application. To maximize drug efficacy, a novel intelligent prodrug delivery nanoplatform with a tumor microenvironment-cleavable core crosslinking strategy was proposed based on a phenylboronic acid (PBA) modified polyethylene glycol (PEG)-polyglutamic acid (PGlu) polymer with disulfide-bonded CPT, called PBA-PEG-P(Glu-co-GlussCPT). The fabricated nanoplatform was a spherical micelle that could withstand dilution and carry a large number of therapeutic molecules to the tumor tissues, thereby minimizing premature drug release. Moreover, the nanoplatform release 6.2 ± 0.62, 12.4 ± 1.8, 46.7 ± 0.33, and 79.2 ± 1.58% of CPT after incubation in 0.02, 1, 5, and 10 mM dithiothreitol for 24 h, respectively, exhibiting good reduction-sensitivity. Moreover, the nanoplatform exhibited significant antiproliferative activity against tumor cells. In addition, with PBA modification, the nanoplatform demonstrated enhanced endocytosis efficiency. This prodrug nanoplatform also exhibited significant in vivo antitumor efficacy on both murine and human hepatoma xenograft models, without showing significant systemic toxicity but demonstrating good biocompatibility. In other words, this novel intelligent prodrug delivery nanoplatform with tumor microenvironment-cleavable core crosslinking strategy and active targeting strategy based on prodrug polymer PBA-PEG-P(Glu-co-GlussCPT) demonstrated multiple functions and significant potential for antitumor drug delivery. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect