N-Succinyl-chitosan nanoparticles coupled with low-density lipoprotein for targeted osthole-loaded delivery to low-density lipoprotein receptor-rich tumors

Abstract

N-Succinyl-chitosan (NSC) was synthesized and NSC nanoparticles (NPs) with loaded osthole (Ost) (Ost/NSC-NPs) were prepared by emulsion solvent diffusion. Subsequently, low-density lipoprotein (LDL)-mediated NSC-NPs with loaded Ost (Ost/LDL-NSC-NPs) were obtained by coupling LDL with Ost/NSC-NPs through amide linkage. The average particle size of Ost/NSC-NPs was approximately 145 nm, the entrapment efficiency was 78.28%±2.06%, and the drug-loading amount was 18.09%±0.17%. The release of Ost from Ost/NSC-NPs in vitro showed a more evident sustained effect than the native material. The half maximal inhibitory concentration of Ost/LDL-NSC-NPs was only 16.23% that of the free Ost at 24 hours in HepG2 cells. Ost inhibited HepG2 cell proliferation by arresting cells in the synthesis phase of the cell cycle and by triggering apoptosis. Cellular uptake and subcellular localization in vitro and near-infrared fluorescence real-time imaging in vivo showed that Ost/LDL-NSC-NPs had high targeting efficacy. Therefore, LDL-NSC-NPs are a promising system for targeted Ost delivery to liver tumor.

Osthole Induces Cell Cycle Arrest and Inhibits Migration and Invasion via PTEN/Akt Pathways in Osteosarcoma

“…Osthole has been shown to exert a wide variety of biological effects, such as anti-seizure, anti-osteoporosis and anti-inflammation [10,11,12,13]. It has been well documented that osthole inhibits the growth and proliferation of various cancer cells through inducing apoptosis or cell cycle arrest [14,15]. Moreover, osthole derivative NBM-T-BMX-OS01 sensitizes A549 cells to cisplatin [16].…”

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

“…LDL was also utilized to modify osthole-loading N-succinyl chitosan NPs, attaining high targeting efficacy indicated by investigations in vitro and in vivo. 228 Hepatic arterial infusion of LDL-based NPs was employed for docosahexaenoic acid (DHA) transporting. 229 LDL-DHA showed selective cytotoxicity against rat (H4IIE), mouse (Hepa1C7, TIB-75) and human (SK-Hep1) HCC cells, and its hepatic artery injection generated improved therapeutic and biologic effects compared with LDL NPs loaded with triolein or sham surgery controls.…”

Distinctive polymer micelle designed for siRNA delivery and reversal of MDR1 gene-dependent multidrug resistance

“…Doxorubicin hydrochloride (Dox‐HCl) was supplied by Dalian Meilun Biotech (Dalian, China). NSC was synthesized in our laboratory as previously reported . PLL (molecular weight, 3.5 kDa) was supplied by Guilin Peptide Technology (Guilin, China).…”

“…NSC was synthesized based on CS using our previously reported procedure . To conjugate NSC to PLL, 0.4 g of NSC was dissolved in 25 mL of distilled water at room temperature.…”