title: Superparamagnetic hollow hybrid nanogels as a potential guidable vehicle system of stimuli-mediated MR imaging and multiple cancer therapeutics.
abstract: Hollow hybrid nanogels were prepared first by the coassembly of the citric acid-coated superparamagnetic iron oxide nanoparticles (SPIONs, 44 wt %) with the graft copolymer (56 wt %) comprising acrylic acid and 2-methacryloylethyl acrylate units as the backbone and poly(ethylene glycol) and poly(N-isopropylacrylamide) as the grafts in the aqueous phase of pH 3.0 in the hybrid vesicle structure, followed by in situ covalent stabilization via the photoinitiated polymerization of MEA residues within vesicles. The resultant hollow nanogels, though slightly swollen, satisfactorily retain their structural integrity while the medium pH is adjusted to 7.4. Confining SPION clusters to such a high level (44 wt %) within the pH-responsive thin gel layer remarkably enhances the transverse relaxivity (r2) and renders the MR imaging highly pH-tunable. For example, with the pH being adjusted from 4.0 to 7.4, the r2 value can be dramatically increased from 138.5 to 265.5 mM(-1) s(-1). The DOX-loaded hybrid nanogels also exhibit accelerated drug release in response to both pH reduction and temperature increase as a result of the substantial disruption of the interactions between drug molecules and copolymer components. With magnetic transport guidance toward the target and subsequent exposure to an alternating magnetic field, this DOX-loaded nanogel system possessing combined capabilities of hyperthermia and stimuli-triggered drug release showed superior in vitro cytotoxicity against HeLa cells as compared to the case with only free drug or hyperthermia alone. This work demonstrates that the hollow inorganic/organic hybrid nanogels hold great potential to serve as a multimodal theranostic vehicle functionalized with such desirable features as the guidable delivery of stimuli-mediated diagnostic imaging and hyperthermia/chemotherapies.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 300, Taiwan.
authors.forename: Wen-Hsuan
authors.initials: WH
authors.lastname: Chiang
authors.forename: Viet Thang
authors.initials: VT
authors.lastname: Ho
authors.forename: Hsin-Hung
authors.initials: HH
authors.lastname: Chen
authors.forename: Wen-Chia
authors.initials: WC
authors.lastname: Huang
authors.forename: Yi-Fong
authors.initials: YF
authors.lastname: Huang
authors.forename: Sung-Chyr
authors.initials: SC
authors.lastname: Lin
authors.forename: Chorng-Shyan
authors.initials: CS
authors.lastname: Chern
authors.forename: Hsin-Cheng
authors.initials: HC
authors.lastname: Chiu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D019343:Citric Acid / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005290:Ferric Compounds / Q000737:chemistry; D005782:Gels / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D016062:Porosity; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D005290:Ferric Compounds; D005782:Gels; D058185:Magnetite Nanoparticles; D009942:Organometallic Compounds; D011108:Polymers; C000499:ferric oxide; D019343:Citric Acid