title: pH-Sensitive mesoporous silica nanoparticles anticancer prodrugs for sustained release of ursolic acid and the enhanced anti-cancer efficacy for hepatocellular carcinoma cancer.
abstract: Ursolic acid (UA) as a nature product exhibits good anti-cancer activity, low toxicity, and good liver protection features. However, the low-solubility and poor bioavailability restrict its further clinical application. To overcome this problem, a pH-sensitive prodrug delivery system (UA@MSN-UA) that incorporated acid-sensitive linkage between drug and silica-based mesoporous nanosphere (MSN) was successfully designed and synthesized. The physicochemical properties of the UA@MSN-UA nanoparticles were investigated for shape, particle size, zeta potential, nitrogen adsorption-desorption and infrared (IR) spectroscopy. The nanoparticles were further evaluated for in vitro cytotoxicity, including proliferation inhibition, cell cycle distribution and apoptotic effects against human hepatocellular carcinoma HepG2 cells. The TEM image showed that the size of synthesized MSN nanoparticle was a near-spherical shape with ~100nm diameter. In vitro cytotoxicity testing demonstrated that UA@MSN-UA nanoparticles prodrug exhibited higher proliferation inhibition, cell cycle arrest at the G2/M phase and significantly caused the early and late apoptosis in HepG2 cells, which would be contributed to high loading capacity, high cellular uptake and sustained release of UA. Overall, the UA-modified MSN prodrug delivery system can be a promising drug carrier for improving the bioavailability of UA, and further enhance its anti-cancer efficacy.
authors: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, China; Fujian Provincial Key Laboratory of Cancr Metastasis Chemoprevention, Fuzhou University, Fuzhou, China.
authors: Tao
authors: T
authors: Li
authors: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, China; Fujian Provincial Key Laboratory of Cancr Metastasis Chemoprevention, Fuzhou University, Fuzhou, China.
authors: Xiufen
authors: X
authors: Chen
authors: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, China; Fujian Provincial Key Laboratory of Cancr Metastasis Chemoprevention, Fuzhou University, Fuzhou, China.
authors: Yajun
authors: Y
authors: Liu
authors: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, China; Fujian Provincial Key Laboratory of Cancr Metastasis Chemoprevention, Fuzhou University, Fuzhou, China.
authors: Lulu
authors: L
authors: Fan
authors: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, China.
authors: Liqing
authors: L
authors: Lin
authors: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, China.
authors: Yu
authors: Y
authors: Xu
authors: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, China.
authors: Sijia
authors: S
authors: Chen
authors: Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350108, China; Fujian Provincial Key Laboratory of Cancr Metastasis Chemoprevention, Fuzhou University, Fuzhou, China. Electronic address: shaojingwei@fzu.edu.cn.
authors: Jingwei
authors: J
authors: Shao
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D014315:Triterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000097245:Ursolic Acid
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011355:Prodrugs; D012822:Silicon Dioxide; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: Amino modification; Cancer therapy; Hepatocellular carcinoma (HCC); Mesoporous silica nanoparticles; Ursolic acid