title: Hydrazone-bearing PMMA-functionalized magnetic nanocubes as pH-responsive drug carriers for remotely targeted cancer therapy in vitro and in vivo.
abstract: To develop vehicles for efficient chemotherapeutic cancer therapy, we report a remotely triggered drug delivery system based on magnetic nanocubes. The synthesized magnetic nanocubes with average edge length of around 30 nm acted as cores, whereas poly(methyl methacrylate) (PMMA) was employed as an intermediate coating layer. Hydrazide was then tailored onto PMMA both for doxorubicin (DOX) loading and pH responsive drug delivery via the breakage of hydrazine bonds. The successful fabrication of the pH responsive drug carrier was confirmed by transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and magnetic hysteresis loops, respectively. The carrier was stable at neutral environment and doxorubicin released at pH of 5.0. Cell viability assay and confocal laser scanning microscopy observations demonstrated that the loaded DOX could be efficiently released after cellular endocytosis and induced cancer cells apoptosis thereby. More importantly, the carrier could be guided to the tumor tissue site with an external magnetic field and led to efficient tumor inhibition with low side effects, which were reflected by magnetic resonance imaging (MRI), change of tumor size, TUNEL staining, and H&E staining assays, respectively. All results suggest that hydrazide-tailoring PMMA-coated magnetic nanocube would be a promising pH-responsive drug carrier for remotely targeted cancer therapy in vitro and in vivo.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University , Chongqing 400044, P. R. China.
authors.forename: Xingwei
authors.initials: X
authors.lastname: Ding
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Jinghua
authors.initials: J
authors.lastname: Li
authors.forename: Zhong
authors.initials: Z
authors.lastname: Luo
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.forename: Beilu
authors.initials: B
authors.lastname: Zhang
authors.forename: Junjie
authors.initials: J
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Kaiyong
authors.initials: K
authors.lastname: Cai
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D014183:Transplantation, Heterologous
chemical_list: D000903:Antibiotics, Antineoplastic; D001672:Biocompatible Materials; D004337:Drug Carriers; D006835:Hydrazones; D058185:Magnetite Nanoparticles; D004317:Doxorubicin; D019904:Polymethyl Methacrylate; D016650:Fluorescein-5-isothiocyanate