期刊
JOURNAL OF CONTROLLED RELEASE
卷 323, 期 -, 页码 333-349出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2020.04.027
关键词
Chemo-photodynamic therapy; ROS-responsive; Chlorin e6; Poly (propylene sulfide); Chondroitin sulfate
资金
- Major Research Project of Shandong Province, P.R.China [2018GSF118004]
- Shandong Provincial Major Science AMP
- Technology Innovation Project, P.R.China [2018CXGC1411]
- Major Basic Research Projects of Shandong Natural Science Foundation, P.R.China [ZR2018ZC0232]
- China Postdoctoral Science Foundation [2019M652413]
To improve the anti-cancer therapeutic effect of nanosystems for chemo-photodynamic therapy, there remain several hurdles to be addressed, e.g., limited co-loading efficiency, insufficient stimulus-responsiveness and lack of synergetic effect. This work reported novel reactive-oxygen-species (ROS)-responsive chlorin e6 (Ce6) and paclitaxel (PTX) co-encapsulated chondroitin sulfate-g-poly (propylene sulfide) nanoparticles (CP/ChS-g-PPS NPs), wherein the drug loading efficiencies of Ce6 and PTX were as high as 14.93% and 24.31%, respectively. To enlarge the ROS signal at tumor sites thus enhancing the ROS-responsiveness of ChS-g-PPS NPs, near-infrared (NIR) light was utilized to induce Ce6 to produce more ROS to destruct the NPs. Our data showed that the photo-triggered self-destructive property of NPs helped drugs to spread deeper in tumors upon laser irradiation, making the NPs promising to thoroughly remove tumor cells. CP/ChS-g-PPS NPs exhibited a synergetic chemo-photodynamic therapy effect in vitro, which was suggested by the combination indexes of PTX and Ce6 lower than 1 when 20-80% inhibition rates of MCF-7 cells were achieved. As for the in vivo antitumor activity, the tumor inhibition rates of CP/ChS-g-PPS NPs (with laser irradiation) were as high as 92.76% and 88.57% in 4T1 bearing BALB/c mice and MCF-7 bearing BALB/c nude mice, respectively, which were significantly higher than those of other treatment groups. This work provided a simple yet effective strategy to develop photo-triggered ROS-responsive NPs for synergetic chemo-photodynamic therapy with quick ROS-responsive self-destruction, spatiotemporally controllability, reduced off-target toxicity, and desirable therapeutic effect.
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