title: A novel redox-sensitive system based on single-walled carbon nanotubes for chemo-photothermal therapy and magnetic resonance imaging.
abstract: Recently, nanomaterials with multiple functions, such as drug carrier, magnetic resonance imaging (MRI) and optical imaging, and photothermal therapy, have become more and more popular in cancer research. In this work, a novel redox-sensitive system constructed from hyaluronic acid (HA), single-walled carbon nanotubes (SWCNTs), doxorubicin (DOX), and gadolinium (Gd) was successfully developed. Herein, HA-modified SWCNTs (SWCNTs-HA) was first synthesized, and then DOX was conjugated with HA by disulfide bond (SWCNTs-HA-ss-DOX). Finally, MRI contrast agents, Gd(3+)-ion loading occurred through the sidewall defects of SWCNTs, whose cytotoxicity could be sequestered within the SWCNTs. In vitro release of DOX showed that this system accomplished much faster drug release under reducing condition. Confocal microscopy analysis confirmed that Gd/SWCNTs-HA-ss-DOX were capable of simultaneously delivering DOX and SWCNTs into Michigan Cancer Foundation-7 cells via HA receptor-mediated endocytosis followed by rapid transport of cargoes into the cytosol. Enhanced cytotoxicity of Gd/SWCNTs-HA-ss-DOX further proved that the sensitive system was more potent for intracellular drug delivery as compared with the insensitive control. Meanwhile, tumor cell killing potency was improved when Gd/SWCNTs-HA-ss-DOX were combined with near-infrared irradiation, with IC50 of 0.61 µg/mL at 48 hours. In vivo investigation demonstrated that Gd/SWCNTs-HA-ss-DOX could effectively accumulate in tumor sites and possessed the greatest synergistic antitumor efficacy, especially under the 808 nm laser irradiation. More importantly, this system could be used as a contrast agent for MRI to identify the location and extent of tumor tissues. These results suggested that Gd/SWCNTs-HA-ss-DOX might be a promising system for targeting chemo-photothermal therapy and MRI diagnosis in future clinical anticancer applications.
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, Henan Province, Zhengzhou, People's Republic of China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, Henan Province, Zhengzhou, People's Republic of China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, Henan Province, Zhengzhou, People's Republic of China.
authors.forename: Junxiao
authors.initials: J
authors.lastname: Ren
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, Henan Province, Zhengzhou, People's Republic of China.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, Henan Province, Zhengzhou, People's Republic of China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, Henan Province, Zhengzhou, People's Republic of China.
authors.forename: Qianhua
authors.initials: Q
authors.lastname: Feng
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, Henan Province, Zhengzhou, People's Republic of China.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, Henan Province, Zhengzhou, People's Republic of China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Shan
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, Henan Province, Zhengzhou, People's Republic of China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, Henan Province, Zhengzhou, People's Republic of China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, People's Republic of China.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D003287:Contrast Media / Q000008:administration & dosage; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D005682:Gadolinium / Q000008:administration & dosage; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000737:chemistry; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010084:Oxidation-Reduction; D010789:Phototherapy / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D003287:Contrast Media; D004337:Drug Carriers; D037742:Nanotubes, Carbon; D012333:RNA, Messenger; D004317:Doxorubicin; D006820:Hyaluronic Acid; D005682:Gadolinium
keywords: cancer diagnosis; multifunctional; redox-responsive; synergistic effect; tumor targeting