Specifically Increased Paclitaxel Release in Tumor and Synergetic Therapy by a Hyaluronic Acid–Tocopherol Nanomicelle
| Autor: | Jie Yang, Hanbo Zhang, Zuhua Wang, Chunqi Zhu, Qingpo Li, Fenfen Kong, Jian You, Lihua Luo, Yong-Zhong Du, Wei Li, Xiaomeng Guo |
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| Rok vydání: | 2017 |
| Předmět: |
Materials science
Paclitaxel Tocopherols 02 engineering and technology 010402 general chemistry 01 natural sciences Micelle chemistry.chemical_compound Drug Delivery Systems In vivo Cell Line Tumor Hyaluronic acid Humans Tissue Distribution General Materials Science Hyaluronic Acid Micelles Drug Carriers Glutathione 021001 nanoscience & nanotechnology 0104 chemical sciences chemistry Biochemistry Drug delivery Cancer cell 0210 nano-technology Linker |
| Zdroj: | ACS Applied Materials & Interfaces. 9:20385-20398 |
| ISSN: | 1944-8252 1944-8244 |
| DOI: | 10.1021/acsami.7b02606 |
| Popis: | Recently, interest in tumor-targeted and site-specific drug release from nanoparticles as a means of drug delivery has increased. In this study, we report a smart nanosized micelle formed by hyaluronic acid (HA) conjugated with d-α-tocopherol succinate (TOS) using a disulfide bond as the linker (HA-SS-TOS, HSST). HSST micelles can specifically bind to the CD44 receptors that are overexpressed by cancer cells. The high levels of glutathione (GSH) in tumor cells selectively break the disulfide bond linker. This effect results in the synchronous release of the payload and a TOS fragment. These two components subsequently demonstrate synergetic anticancer activity. First, we demonstrate that drug release from HSST occurs rapidly in physiological high redox conditions and inside cancer cells. Significant GSH-triggered drug release was also observed in vivo. Furthermore, an in vivo biodistribution study indicated that the HSST micelles efficiently accumulated at the tumor sites, primarily due to an enhanced permeability and retention effect and the efficient binding to the cancer cells that overexpressed the CD44 receptor. Interestingly, the synchronous release of paclitaxel (PTX) and the TOS fragment from the PTX-loaded HSST caused synergetic tumor cell killing and tumor growth inhibition. Our work presents a useful candidate for a drug delivery system that can specifically accumulate at tumor tissue, selectively release its payload and a TOS fragment, and thus display a synergetic anticancer effect. |
| Databáze: | OpenAIRE |
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