The development and evaluation of hyaluronic acid coated mitochondrial targeting liposomes for celastrol delivery

Abstract

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.

Keywords:

• Celastrol
• mitochondrial targeting
• tumor targeting
• delivery system
• anticancer effect

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethical approval statement

All animals were housed in a specific pathogen free environment (ventilated room, 24 ± 2 °C, 55-65% humidity, 12 h light/dark cycle and had free access to standard water and food (SYXK 2017-0067). The procedures in accordance with the “Regulations of Hubei province on the administration of laboratory animals” and “Guiding principles in the Care and Use of Animals” (China) were approved by the Laboratory Animal Ethics Committee of Hubei University of Chinese Medicine (HUCMS202109020).

Supporting materials

Characterization of CT; Screening the mass ratios of CT:SPC; Screening the mole ratios of HA:CT; Storage stability of C-TL and C-TL/HA at 4 °C; Representative images of the HE-stained normal tissues after treatment.

Additional information

Funding

This work was supported by National Natural Science Fundation of China (Grant Nos. 31900919, U21A20297).