title: Drug-loaded and superparamagnetic iron oxide nanoparticle surface-embedded amphiphilic block copolymer micelles for integrated chemotherapeutic drug delivery and MR imaging.
abstract: We report on the fabrication of organic/inorganic hybrid micelles of amphiphilic block copolymers physically encapsulated with hydrophobic drugs within micellar cores and stably embedded with superparamagnetic iron oxide (SPIO) nanoparticles within hydrophilic coronas, which possess integrated functions of chemotherapeutic drug delivery and magnetic resonance (MR) imaging contrast enhancement. Poly(ε-caprolactone)-b-poly(glycerol monomethacrylate), PCL-b-PGMA, and PCL-b-P(OEGMA-co-FA) amphiphilic block copolymers were synthesized at first by combining ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP), and post- modification techniques, where OEGMA and FA are oligo(ethylene glycol) monomethyl ether methacrylate and folic acid-bearing moieties, respectively. A model hydrophobic anticancer drug, paclitaxel (PTX), and 4 nm SPIO nanoparticles were then loaded into micellar cores and hydrophilic coronas, respectively, of mixed micelles fabricated from PCL-b-PGMA and PCL-b-P(OEGMA-co-FA) diblock copolymers by taking advantage of the hydrophobicity of micellar cores and strong affinity between 1,2-diol moieties in PGMA and Fe atoms at the surface of SPIO nanoparticles. The controlled and sustained release of PTX from hybrid micelles was achieved, exhibiting a cumulative release of ~61% encapsulated drugs (loading content, 8.5 w/w%) over ~130 h. Compared to that of surfactant-stabilized single SPIO nanoparticles (r(2) = 28.3 s(-1) mM(-1) Fe), the clustering of SPIO nanoparticles within micellar coronas led to considerably enhanced T(2) relaxivity (r(2) = 121.1 s(-1) mM(-1) Fe), suggesting that hybrid micelles can serve as a T(2)-weighted MR imaging contrast enhancer with improved performance. Moreover, preliminary experiments of in vivo MR imaging were also conducted. These results indicate that amphiphilic block copolymer micelles surface embedded with SPIO nanoparticles at the hydrophilic corona can act as a new generation of nanoplatform integrating targeted drug delivery, controlled release, and disease diagnostic functions.
authors: CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors: Jinming
authors: J
authors: Hu
authors: Yinfeng
authors: Y
authors: Qian
authors: Xiaofeng
authors: X
authors: Wang
authors: Tao
authors: T
authors: Liu
authors: Shiyong
authors: S
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D003287:Contrast Media / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008279:Magnetic Resonance Imaging / Q000379:methods*; D059346:Magnets / Q000737:chemistry*; D008823:Micelles; D008958:Models, Molecular; D008968:Molecular Conformation; D017239:Paclitaxel / Q000737:chemistry / Q000378:metabolism; D058105:Polymerization; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D004337:Drug Carriers; D005290:Ferric Compounds; D008823:Micelles; D011108:Polymers; C000499:ferric oxide; D017239:Paclitaxel