期刊
DRUG DELIVERY
卷 30, 期 1, 页码 -出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10717544.2022.2162156
关键词
Celastrol; mitochondrial targeting; tumor targeting; delivery system; anticancer effect
A novel multistage-targeted celastrol delivery system (C-TL/HA) was developed by electrostatic binding of hyaluronic acid (HA) to celastrol-loaded cationic liposomes. The study showed that C-TL/HA successfully delivered celastrol into mitochondria, activated apoptosis of mitochondrial pathway, and exhibited higher tumor inhibition efficiency and lower toxic side effects compared with free celastrol. The HA coating not only improved stability and safety in vivo, but also enhanced drug uptake and tumor targeting through recognition of CD44 receptors.
In order to precisely deliver celastrol into mitochondria of tumor cells, improve antitumor efficacy of celastrol and overcome its troublesome problems in clinical application, a novel multistage-targeted celastrol delivery system (C-TL/HA) was developed via electrostatic binding of hyaluronic acid (HA) to celastrol-loaded cationic liposomes composed of natural soybean phosphatidylcholine and cholesterol modified with mitochondrial targeting molecular TPP. Study results in this article showed that C-TL/HA successfully transported celastrol into mitochondria, effectively activated apoptosis of mitochondrial pathway, exerted higher tumor inhibition efficiency and lower toxic side effects compared with free celastrol. More importantly, HA coating not only enabled this delivery system to have good stability and safety in vivo, but also increased drug uptake and facilitated tumor targeting through recognizing CD44 receptors rich on the surface of tumor cells. Conclusively, this HA-coated mitochondrial targeting liposomes may provide a prospect for the clinical application of celastrol in tumor therapy.
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