title: Functionalized Multiwalled Carbon Nanotubes as Carriers of Ruthenium Complexes to Antagonize Cancer Multidrug Resistance and Radioresistance.
abstract: Multidrug resistance and radioresistance are major obstacles for successful cancer therapy. Due to the unique characteristics of high surface area, improved cellular uptake, and the possibility to be easily bound with therapeutics, carbon nanotubes (CNTs) have attracted increasing attention as potential nanodrug delivery systems. In this study, a CNT-based radiosensitive nanodrug delivery system was rationally designed to antagonize the multidrug resistance in hepatocellular carcinoma. The nanosystem was loaded with a potent anticancer ruthenium polypyridyl complex (RuPOP) via π-π interaction and formation of a hydrogen bond. The functionalized nanosystem (RuPOP@MWCNTs) enhanced the cellular uptake of RuPOP in liver cancer cells, especially drug-resistant R-HepG2 cells, through endocytosis. Consistently, the selective cellular uptake endowed the nanosystem amplified anticancer efficacy against R-HepG2 cells but not in normal cells. Interestingly, RuPOP@MWCNTs significantly enhanced the anticancer efficacy of clinically used X-ray against R-HepG2 cells through induction of apoptosis and G0/G1 cell cycle arrest, with the involvement of ROS overproduction, which activated several downstream signaling pathways, including DNA damage-mediated p53 phosphorylation, activation of p38, and inactivation of AKT and ERK. Moreover, the nanosystem also effectively reduces the toxic side effects of loaded drugs and prolongs the blood circulation in vivo. Taken together, the results demonstrate the rational design of functionalized carbon nanotubes and their application as effective nanomedicine to overcome cancer multidrug resistance.
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Yanxian
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Lilan
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Zhennan
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Chen
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy / Q000379:methods; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D058726:Nanoconjugates / Q000737:chemistry* / Q000648:ultrastructure; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D012428:Ruthenium / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D053769:Nanocapsules; D058726:Nanoconjugates; D037742:Nanotubes, Carbon; D011838:Radiation-Sensitizing Agents; D012428:Ruthenium
keywords: anticancer; carbon nanotube; drug delivery system; drug resistance; radioresistance