Multifunctional mesoporous silica nanoparticles modified with tumor-shedable hyaluronic acid as carriers for doxorubicin.
In this paper, a CD44-targeted and redox-responsive drug delivery system based on mesoporous silica nanoparticles (MSNs) was synthesized by conjugating tumor-shedable hyaluronic acid (HA) on the surface of MSNs via disulfide bonds. Doxorubicin hydrochloride (DOX·HCl) was physically encapsulated into HA modified MSNs (MSNs/SS/HA@DOX) as a model drug. MSNs/SS/HA@DOX (40nm) had a high drug loading (14.1%) and redox-responsive drug release property. The cellular uptake behaviors of MSNs/SS/HA@DOX by HeLa and LO2 cells were evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM). MSNs/SS/HA@DOX exhibited higher cellular uptake efficacy via CD44-mediated endocytosis by HeLa cells (CD44 over-expressed cells) than by LO2 cells (CD44 deficient cells). The in vitro cytotoxicity assay demonstrated that MSNs/SS/HA@DOX exhibited higher cytotoxicity to HeLa cells than to LO2 cells. These results indicated that MSNs/SS/HA@DOX might be promising as a multifunctional drug delivery system to improve the anti-tumor efficacy of chemotherapeutic drugs.
School of Pharmacy, Binzhou Medical University, Yantai, PR China.
Jing
J
Zhang
School of Pharmacy, Binzhou Medical University, Yantai, PR China.
Yujie
Y
Sun
School of Pharmacy, Binzhou Medical University, Yantai, PR China.
Baocheng
B
Tian
School of Pharmacy, Binzhou Medical University, Yantai, PR China.
Keke
K
Li
School of Pharmacy, Binzhou Medical University, Yantai, PR China.
Lele
L
Wang
School of Pharmacy, Binzhou Medical University, Yantai, PR China.
Yan
Y
Liang
School of Pharmacy, Binzhou Medical University, Yantai, PR China. Electronic address: hanjingtian002@163.com.
Jingtian
J
Han
D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D005453:Fluorescence; D006367:HeLa Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D055672:Static Electricity
D004337:Drug Carriers; D012822:Silicon Dioxide; D004317:Doxorubicin; D006820:Hyaluronic Acid
CD44-targeted; Doxorubicin; Drug delivery system; Mesoporous silica nanoparticles; Redox-responsive