title: Multifunctional mesoporous silica nanoparticles mediated co-delivery of paclitaxel and tetrandrine for overcoming multidrug resistance.
abstract: The objective of the study is to fabricate multifunctional mesoporous silica nanoparticles for achieving co-delivery of conventional antitumor drug paclitaxel (PTX) and the multidrug resistance reversal agent tetrandrine (TET) expecting to overcome multidrug resistance of MCF-7/ADR cells. The nanoparticles were facile to prepare by self-assemble in situ drug loading approach. Namely, PTX and TET were solubilized in the cetyltrimethylammonium bromide (CTAB) micelles and simultaneously silica resources hydrolyze and condense to form nanoparticles. The obtained nanoparticles, denoted as PTX/TET-CTAB@MSN, exhibited pH-responsive release property with more easily released in the weak acidic environment. Studies on cellular uptake of nanoparticles demonstrated TET could markedly increase intracellular accumulation of nanoparticles. Furthermore, the PTX/TET-CTAB@MSN suppressed tumor cells growth more efficiently than only delivery of PTX (PTX-CTAB@MSN) or the free PTX. Moreover, the nanoparticle loading drugs with a PTX/TET molar ratio of 4.4:1 completely reversed the resistance of MCF-7/ADR cells to PTX and the resistance reversion index was 72.3. Mechanism research showed that both TET and CTAB could arrest MCF-7/ADR cells at G1 phase; and besides PTX arrested cells at G2 phase. This nanocarrier might have important potential in clinical implications for co-delivery of multiple drugs to overcome MDR.
authors.affiliation: Department of Pharmacy, Qilu Hospital of Shandong University, 107 Wenhua Xilu, Jinan 250012, PR China.
authors.forename: Lejiao
authors.initials: L
authors.lastname: Jia
authors.affiliation: Key Laboratory of Chemical Biology of Ministry of Education, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, PR China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, PR China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, PR China. Electronic address: qlchangping@163.com.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, PR China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, PR China.
authors.forename: Hejian
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, Qilu Hospital of Shandong University, 107 Wenhua Xilu, Jinan 250012, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D044182:Benzylisoquinolines / Q000008:administration & dosage* / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D065546:Drug Liberation; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D016062:Porosity; D012822:Silicon Dioxide / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D002593:Cetrimonium Compounds; D004337:Drug Carriers; D008823:Micelles; C009438:tetrandrine; D012822:Silicon Dioxide; D017239:Paclitaxel; D000077286:Cetrimonium
keywords: Co-delivery; Mesoporous silica nanoparticles; Multidrug resistance; Paclitaxel; Tetrandrine