title: Fabrication and in vitro characterization of gadolinium-based nanoclusters for simultaneous drug delivery and radiation enhancement.
abstract: We report the synthesis of a gadolinium hydroxide (Gd(OH)3) nanorod based doxorubicin (Dox) delivery system that can enhance both magnetic resonance imaging contrast and radiation sensitivity. A simple and cost effective wet-chemical method was utilized in the presence of manganese (Mn) ions and Dox to produce the Gd(OH)3:Mn·Dox nanocluster structure. The Gd(OH)3:Mn·Dox nanocluster was composed of Mn-doped Gd(OH)3 nanorods arranged in parallel with Dox as a linker molecule between the adjacent nanorods. No other studies have utilized Dox as both the linker and therapeutic molecule in a nanostructure to date. The Gd(OH)3 nanorod is reported to have no significant cellular or in vivo toxicity, which makes it an ideal base material for this biomedical application. The Gd(OH)3:Mn·Dox nanocluster exhibited paramagnetic behavior and was stable in a colloidal solution. The nanocluster also enabled high Dox loading capacity and specifically released Dox in a sustained and pH-dependent manner. The positively charged Gd(OH)3:Mn·Dox nanoclusters were readily internalized into MDA-MB-231 breast cancer cells via endocytosis, which resulted in intracellular release of Dox. The released Dox in cells was effective in conferring cytotoxicity and inhibiting proliferation of cancer cells. Furthermore, a synergistic anticancer effect could be observed with radiation treatment. Overall, the Gd(OH)3:Mn·Dox nanocluster drug delivery system described herein may have potential utility in clinics as a multifunctional theranostic nanoparticle with combined benefits in both diagnosis and therapy in the management of cancer.
authors.affiliation: Department of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Shannon S
authors.initials: SS
authors.lastname: Yoo
authors.forename: Linghong
authors.initials: L
authors.lastname: Guo
authors.forename: Xuejun
authors.initials: X
authors.lastname: Sun
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Shaw
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Yuan
authors.forename: Raimar
authors.initials: R
authors.lastname: Löbenberg
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Roa
mesh_terms: D004317:Doxorubicin; D016503:Drug Delivery Systems; D005682:Gadolinium / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D053758:Nanoparticles; D000068936:Theranostic Nanomedicine
chemical_list: D004317:Doxorubicin; D005682:Gadolinium