期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 188, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.colsurfb.2019.110722
关键词
Carrier-free nanoparticles; 7-Ethyl-10-hydroxycamptothecin; Chlorin e6; Synergistic efficacy; Self-assembly mechanism
资金
- National Natural Science Foundation of China [21473085]
- Natural Science Foundation of Shandong Province of China [ZR2017BH065, ZR2016CL14]
- Project of Shandong Province Higher Educational Science and Technology Program [J17KA234]
- Open Project of Shandong Collaborative Innovation Center for Antibody Drugs [CIC-AD1831, CIC-AD1832]
- Tai-Shan Scholar Research Fund of Shandong Province of China [319190201]
The combination therapy strategy based on both chemotherapy and photodynamic therapy (PDT) exhibits great potential for advanced cancer treatment. Multimodal nanodrug delivery systems based on both chemotherapeutic drug and photodynamic agent have been proven to possess excellent synergistic efficacy. In this study, 7-ethyl-10-hydroxycamptothecin (SN38) and chlorin e6 (Ce6) were co-assembled into novel carrier-free nanoparticles (SN38/Ce6 NPs) via simple antisolvent precipitation method. As expected, SN38/Ce6 NPs exhibited uniform morphology with a particle size of around 150 nm and a zeta potential of about -30 mV, good stability in aqueous solution/at lyophilized state and high cellular uptake efficiency against murine mammary carcinoma (4T1) cell lines. Besides, enhanced singlet oxygen generation capacity of the nanoparticles was both observed in test-tube and in 4T1 cell lines in contrast with Ce6 injection. Moreover, a similar to 85 % inhibition rate of SN38/Ce6 NPs with laser was detected, which was significantly higher (P < 0.05) than those without laser (similar to 65 %) and injections (less than 20 %), verified the excellent synergistic antitumor efficacy of the nanoparticles due to combined chemo-photodynamic therapy, enhanced tumor accumulation and higher cellular internalization. Notably, chemical thermodynamic method and molecular dynamics (MD) simulations supplied solid data and visual images to estimate the driving forces for the self-assembly process of the carrier-free nanoparticles as primary hydrophobic interactions (pi-pi stacking) and subordinate hydrogen bonds. Conclusively, the above self-assembled carrier-free nanoparticles represented a promising synergistic anticancer strategy capable of maximal therapeutic efficacy and minimal systemic toxicity. Moreover, the application of thermodynamic method together with MD simulations in the investigation of NPs self-assembly process also provided new ideas for the assembly mechanism exploration of more complicated nanodrug delivery system.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据