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.

Cel-CS1K: A Celastrol–Chitosan Conjugate for Treating Diet-Induced Obesity

“…Recently, researchers have increasingly focused on the role of celastrol in weight loss through multiple pathway (e.g., leptin sensitivity, energy expenditure, and appetite control). − However, the potential for the clinical use of celastrol is largely limited by its toxicity and poor water solubility. Fortunately, several pharmaceutic strategies have been developed to circumvent these problems, including liposomes, − nanoencapsulation, polymer drugs, and polymeric micelles. , Various celastrol-loaded carriers greatly improve the bioavailability of celastrol and significantly reduce the adverse reactions of drugs. − …”

Orally administered dual-targeted astaxanthin nanoparticles as novel dietary supplements for alleviating hepatocyte oxidative stress

“…21 Liposomes have been used for celastrol delivery by incorporating TPP-modified cholesterol with natural soy phosphatidylcholine, paving the way for the clinical application of triptolide in tumor therapy. 22 Furthermore, researchers have successfully developed novel fluorescent carbon dots with intrinsic mitochondrial targeting capabilities, by employing a one-step hydrothermal treatment of mercaptosuccinic acid, ethylenediamine, and chitosan. 23 The resulting carbon dots enable mitochondrial imaging and photodynamic cancer therapy specifically targeting mitochondria.…”