Selective Intratumoral Drug Release and Simultaneous Inhibition of Oxidative Stress by a Highly Reductive Nanosystem and Its Application as an Anti-tumor Agent.

Abstract

Excessive oxidative stress is always associated with the serious side effects of chemotherapy. In the current study, we developed a vitamin E based strongly reductive nanosystem to increase the loading efficiency of docetaxel (DTX, DTX-VNS), reduce its side toxicity and enhance the antitumor effect. Methods: We used Förster Resonance Energy Transfer (FRET) to reveal the in vivo and in vitro fate of DTX-VNS over time. All FRET images were observed using the Maestro imaging system (CRI, Inc., Woburn, MA) and Fluo-View software (Olympus LX83-FV3000). Results: Through FRET analyzing, we found that our nanosystem showed a selective rapider release of drugs in tumors compared to normal organs due to the higher levels of ROS in tumor cells than normal cells, and the accumulation of DTX at tumor sites in the DTX-VNS group was also notably more than that in the Taxotere group after 24 h injection. Meanwhile, DTX-VNS had a prominently stronger anti-tumor effect in various models than Taxotere, and had a synergistic effect of immunotherapy. Conclusions: Our work presented a useful reference for clinical exploration of the in vivo behavior of nanocarriers (DTX-VNS), inhibition oxidative stress and selective release of drugs at tumor sites, thus reducing the side effects and enhancing the anti-tumor effects.

• Authors: Chunqi Zhu, Lihua Luo, Xindong Jiang, Mengshi Jiang, Zhenyu Luo, Xiang Li, Weigen Qiu, Zhaolei Jin, Tianxiang Shen, Chunlong Li, Qingpo Li, Yunqing Qiu, Jian You
• Journal: Theranostics (Theranostics) Vol. 10 Issue 3 Pg. 1166-1180 ( 2020) ISSN: 1838-7640 [Electronic] Australia
• PMID: 31938058 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Reactive Oxygen Species
• Docetaxel

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Cell Line, Tumor
• Docetaxel (administration & dosage, pharmacology)
• Drug Carriers (chemistry)
• Drug Liberation
• Female
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles (chemistry)
• Neoplasms (drug therapy)
• Oxidative Stress (drug effects)
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)