Redox-responsive PEGylated self-assembled prodrug-nanoparticles formed by single disulfide bond bridge periplocymarin-vitamin E conjugate for liver cancer chemotherapy

Abstract

Periplocymarin (PPM), a cardiac glycoside, has a narrow therapeutic index, poor tumor selectivity and severe cardiovascular toxicity which hinder its wide clinical applications in cancer treatment. Herein, we report novel redox-responsive prodrug-nanoparticles (MPSSV-NPs) self-assembled by co-nanoprecipitation of PPM-vitamin E conjugate and a PEG derivative of linoleate (mPEG2000-LA) in water. It was found that the characteristics of PPM-vitamin E nanoparticles (PSSV-NPs) were improved through co-nanoprecipitation with increased percentages of mPEG2000-LA. Moreover, the MPSSV-NPs were optimized according to the in vitro release and cytotoxicity study. Furthermore, the optimized MPSSVNPs dramatically enhanced the circulation time and tumor distribution of PSSV-NPs after single intravenous injection. The in vivo studies in malignant H 22 -bearing mice revealed that MPSSV-NPs could effectively suppress tumor growth without causing obvious systemic toxicity. Altogether, these results suggested that MPSSV-NPs could offer a safe, multifunctional and viable nanoplatform for cardiac glycosides in cancer treatment. ARTICLE HISTORY

Enhanced Oral Bioavailability, Anti-Tumor Activity and Hepatoprotective Effect of 6-Shogaol Loaded in a Type of Novel Micelles of Polyethylene Glycol and Linoleic Acid Conjugate

“…Ginger extractive (10% gingerol) was purchased from Nanjing Zelang Biological Technology Co. Ltd. (Nanjing, China). mPEG 2K -LA was synthesized in our laboratory [32]. (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and trypsin were provided by the Beyotime Institute of Biotechnology (Jiangsu, China).…”

Redox‐responsive glycosylated combretastatin A‐4 derivative as novel tubulin polymerization inhibitor for glioma and drug delivery

“…In the last few decades, redox-responsive drug delivery systems have been designed to target cancers specifically and keep the high therapeutic concentration while reduce side effects (Li et al, 2020). Especially, the disulfide bond-based conjugate has been received increasing attention recently (Li et al, 2018;Sun et al, 2018;Zhang et al, 2017), which is stable in the blood and normal tissues (low reductive conditions) (Yang, Sun, et al, 2020). Compared to normal cells, the tumor cells overproduce the glutathione (GSH), which could cause the rapid destruction of the disulfide bond to achieve stimuli-responsiveness (Du et al, 2020).…”

Periplocymarin Induced Colorectal Cancer Cells Apoptosis Via Impairing PI3K/AKT Pathway

“…Periplocymarin (PPM) is isolated from cortex periplocae, the dry root of Periploca sepium Bge, which is traditionally used as antirheumatic and diuretic agent in Chinese medicine (7). Previous studies have indicated that, PPM performed antitumor effects in various of cancer (8,9). For example, it has been found that PPM promoted prostate adenocarcinoma (PC3) cell apoptosis and inhibit proliferation of U937, HCT-8, Bel-7402, BGC823, A549, and A2780 cell lines in vitro with IC50 values of 0.02-0.29 mM (10).…”