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.
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Authors | Lejiao Jia, Zhenyu Li, Jingyi Shen, Dandan Zheng, Xiaona Tian, Hejian Guo, Ping Chang |
Journal | International journal of pharmaceutics
(Int J Pharm)
Vol. 489
Issue 1-2
Pg. 318-30
(Jul 15 2015)
ISSN: 1873-3476 [Electronic] Netherlands |
PMID | 25956050
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier B.V. All rights reserved. |
Chemical References |
- Antineoplastic Agents, Phytogenic
- Benzylisoquinolines
- Cetrimonium Compounds
- Drug Carriers
- Micelles
- tetrandrine
- Silicon Dioxide
- Paclitaxel
- Cetrimonium
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Topics |
- Antineoplastic Agents, Phytogenic
(administration & dosage, chemistry)
- Benzylisoquinolines
(administration & dosage, chemistry)
- Cell Survival
(drug effects)
- Cetrimonium
- Cetrimonium Compounds
(chemistry)
- Drug Carriers
(administration & dosage, chemistry)
- Drug Liberation
- Drug Resistance, Multiple
(drug effects)
- Drug Resistance, Neoplasm
(drug effects)
- Humans
- MCF-7 Cells
- Micelles
- Nanoparticles
(administration & dosage, chemistry)
- Paclitaxel
(administration & dosage, chemistry)
- Porosity
- Silicon Dioxide
(administration & dosage, chemistry)
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