Delivery of paeonol by nanoparticles enhances its in vitro and in vivo antitumor effects

Abstract

Paeonol (Pae; 2′-hydroxy-4′-methoxyacetophenone) has attracted intense attention as a potential therapeutic agent against various cancers. However, the use of Pae is limited owing to its hydrophobicity. Recently, biodegradable polymeric nanoparticles with amphiphilic copolymers have been used as drug carriers; these have better bioavailability and are promising tumor-targeted drug delivery systems. In the current study, we prepared Pae-loaded nanoparticles (Pae-NPs) with amphiphilic block copolymers using nanoprecipitation. The physiochemical characteristics and antitumor effects of nanoparticles were evaluated in different cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed substantial inhibition of cell growth by Pae-NPs. Moreover, lower doses of Pae-NPs inhibited cell growth more efficiently than the equivalent doses of free Pae. Inhibition was characterized by significant elevation of intracellular reactive oxygen species and subsequent inhibition of Akt and regulation of apoptotic proteins, which could be partly reversed by pretreatment with the antioxidant N-acetylcysteine. In vivo results also demonstrated that Pae-NPs could exert much stronger antitumor effects than free Pae. Therefore, Pae-NPs represent a promising delivery system to overcome the low solubility of Pae and enable its use in treating cancer.

Paeonol induces cytoprotective autophagy via blocking the Akt/mTOR pathway in ovarian cancer cells

“…Finally, we generated a xenograft tumour model to determine whether Pae induced anticancer activity in vivo. The xenograft mice were treated with DMSO control (without Pae), Pae (40 mg/kg) 10,16 , or a combination of Pae (40 mg/kg) and HCQ (60 mg/kg) 40 . As shown in Fig.…”

“…Therefore, the rational control of autophagy is of great significance for cancer treatment. Pae has been isolated from the Moutan Cortex, and cumulative evidence suggests that it has effective antitumour activity against various cancer cells 12,15,16 . However, the properties of Pae regarding antiproliferation and the induction of apoptosis and autophagy and the intrinsic relationships in ovarian cancer cells are unknown (Fig.…”

“…Paeonol (Pae; 2′-hydroxy-4′-methoxyacetophenone), a phenolic acid compound derived from the root bark of the Moutan Cortex ( Paeonia suffruticosa ) 7 , has been reported to possess all types of potent properties, including anti-inflammatory 8 , antioxidant 9 , immune regulatory activity 10 , and reverse chemoresistance 11 . Recently, Pae was shown to exhibit favourable anticancer activities in ovarian cancer cells 12,13 and other types of cancer cell lines, such as prostate cancer 14 , melanoma 15 , lung cancer 16 , gastric cancer 17 , and colon cancer 18 . Although the antitumour activity of Pae has been suggested by cumulative evidence, the detailed underlying mechanisms have not been investigated.…”

Biological Activities of Paeonol in Cardiovascular Diseases: A Review

“…Nonetheless, the therapeutic efficacy of paeonol was shown to be limited by the first-pass effect and poor bioavailability due to low aqueous solubility [ 18 ]. To counteract these issues, several nanotechnology-assisted drug delivery systems, for example, microemulsion gel, transethosome, porous microsphere, liquid crystalline nanoparticles, and microsponge, were developed, particularly to treat cancer and skin diseases [ 35 , 36 , 37 , 38 , 39 , 40 ]. These delivery systems had greatly enhanced the therapeutic effects of paeonol due to their high encapsulation capacity and stability, together with better control of drug release and retention time in the targeting tissues.…”

Beneficial Effects Exerted by Paeonol in the Management of Atherosclerosis

“…Results show that these carriers, with high encapsulation efficiency and stability, are biocompatible with paeonol and dramatically raise skin permeability, control release of drug, extend time of drug residence in local tissues, and lower irritation to covered areas, implying superior effects of these complexes in treating skin diseases [ 23 , 26 – 29 ]. Additionally, paeonol-loaded nanoparticles are more effective in cancer treatment when compared to paeonol alone [ 30 ]. Nonetheless, there is no paeonol-related drug delivery system which has been designed and prepared for atherosclerosis therapy up to now.…”