In vitro and in vivo evaluation of antitumor drug-loaded aptamer targeted single-walled carbon nanotubes system.
OBJECTIVE
A multifunctional tumor-targeting drug delivery system employing single-walled carbon nanotubes (SWCNT) as drug carriers, AS1411 as targeting ligand and doxorubicine (DOX) as a model chemotherapy drug was constructed.


METHODS
Firstly, SWCNT were modified with F68 (4.0 mg/ml) by ultrasonic dispersing technology due to the action of hydrophobic force and Van der Waals force, endowing SWCNT water dispersions and biocompatibility. Meanwhile, DOX could be easily absorbed on the surface of SWCNT by the &#960;-&#960; stacking, electrostatic adsorption and hydrophobic interactions. Finally, AS1411 was attached to the surface of DOX-SWCNT by the π-π stacking and electrostatic adsorption to obtain a tumor-targeting delivery system. Cellular uptake, anti-tumor effect in vitro and in vivo, cell cycle and apoptosis and biodistribution of AS1411-DOX-SWCNT were investigated, compared with the DOX solution.


CONCLUSIONS
This AS1411-mediated DOX-loaded SWCNT (AS1411-DOX-SWCNT) delivery system not only retained both optical properties of SWCNT and cytotoxicity of DOX but also could accumulate in tumors, which facilitated combination of chemotherapy and photothermal therapy. AS1411-DOX-SWCNT could effectively promote DOX cellular uptake and then increase intracellular accumulation as a targeting delivery system. AS1411-DOX-SWCNT by NIR laser excited could trigger S phase arrest and the late stage apoptotic on PC3 cancer cells. The investigation in vivo further confirmed that this system possessed higher tumor targeting capacity and antitumor efficacy than DOX, especially with NIR laser irradiation.
Huijuan
H
Zhang
Lin
L
Hou
Xiaojing
X
Jiao
Ji
J
Yandan
Xiali
X
Zhu
Li
L
Hongji
Xiaozhe
X
Chen
Junxiao
J
Ren
Yadan
Y
Xia
School of Pharmaceutical Sciences, Zhengzhou University, No.100, Kexue Road, Zhengzhou 450001, China. zhangzz08@126.com.
Zhenzhong
Z
Zhang
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D052158:Aptamers, Peptide / Q000008:administration & dosage* / Q000627:therapeutic use*; D019540:Area Under Curve; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D037742:Nanotubes, Carbon; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D052158:Aptamers, Peptide; D037742:Nanotubes, Carbon; D004317:Doxorubicin