title: Stable and efficient Paclitaxel nanoparticles for targeted glioblastoma therapy.
abstract: Development of efficient nanoparticles (NPs) for cancer therapy remains a challenge. NPs are required to have high stability, uniform size, sufficient drug loading, targeting capability, and ability to overcome drug resistance. In this study, the development of a NP formulation that can meet all these challenging requirements for targeted glioblastoma multiform (GBM) therapy is reported. This multifunctional NP is composed of a polyethylene glycol-coated magnetic iron oxide NP conjugated with cyclodextrin and chlorotoxin (CTX) and loaded with fluorescein and paclitaxel (PTX) (IONP-PTX-CTX-FL). The physicochemical properties of the IONP-PTX-CTX-FL are characterized by transmission electron microscope, dynamic light scattering, and high-performance liquid chromatography. The cellular uptake of NPs is studied using flow cytometry and confocal microscopy. Cell viability and apoptosis are assessed with the Alamar Blue viability assay and flow cytometry, respectively. The IONP-PTX-CTX-FL had a uniform size of ≈44 nm and high stability in cell culture medium. Importantly, the presence of CTX on NPs enhanced the uptake of the NPs by GBM cells and improved the efficacy of PTX in killing both GBM and GBM drug-resistant cells. The IONP-PTX-CTX-FL demonstrated its great potential for brain cancer therapy and may also be used to deliver PTX to treat other cancers.
authors.affiliation: Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.|Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
authors.forename: Qingxin
authors.initials: Q
authors.lastname: Mu
authors.affiliation: Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Jeon
authors.affiliation: Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu City, 300, Taiwan.
authors.forename: Meng-Hsuan
authors.initials: MH
authors.lastname: Hsiao
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA, 98195, USA.
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Patton
authors.affiliation: Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.
authors.forename: Kui
authors.initials: K
authors.lastname: Wang
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
authors.affiliation: Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.
authors.forename: Miqin
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000068196:Albumin-Bound Paclitaxel / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D003505:Cyclodextrins / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D005290:Ferric Compounds / Q000737:chemistry; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D012604:Scorpion Venoms / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000068196:Albumin-Bound Paclitaxel; D020099:Coated Materials, Biocompatible; D003505:Cyclodextrins; D005290:Ferric Compounds; D012604:Scorpion Venoms; C091539:Chlorotoxin; C000499:ferric oxide
keywords: chlorotoxin; glioblastoma; iron oxide nanoparticles; paclitaxel; β-cyclodextrin