MicroMRI system(0.5 T,MicroMR-18). The in vivo imaging experimentswere carried out on a medical MRI system (Signal exciteTM HD, GE).

Results and discussion1H NMR and GPC results showed that all dendrimers had

controlled compositions and molecular weights. As is shown in Fig.1, the dendrimers have a low PDI, from 1.02 to 1.05. It reveals that thesynthesized dendrimers had a well-defined molecular weight and aprecise number of end groups. The T1s at different concentrations fordendritic contrast agent G1.5-PEG-DTPA-Gd(III) as an example andMagnevist were tested at 0.5 T. The longitudinal ionic relaxivity of thedendritic contrast agent (R1=15.2 mM−1 s−1) was much higherthan Magnevist (R1=4.3 mM−1 s−1) which is the most widely usedMRI contrast agent (Fig. 2).

As shown in Fig. 3, the in vivo MR imaging revealed that the mouseinjected with dendritic CA had much brighter kidney images than thatinjectedwithMagnevist. The signal intensity values of every organwererecorded from 0 to 75 min post injection. The data indicated that thevalues of dendritic CA in renal cortex and liver were significantly higherthan that of Magnevist at all time points examined. It revealed that thedendritic MRI CAG1 had a favorable renal imaging ability and it can alsocirculate in blood vessels for a relatively long time. The mice survivedafter injected G1.5-PEG-DTPA-Gd(III), which could be a preliminaryevidence to prove its biocompatibility. Further cytotoxicity test is inprogress. Thedendritic CAs could also enrich in tumor tissues for theEPReffect [6]. Tumor imagingwith thedendritic CAs having targeting groupslike folic acid are under research.

ConclusionNovel dendritic MRI CAs based on biodegradable dendrimers with a

narrow molecular weight distribution and defined structures, weresuccessfully synthesized. The dendritic CA G1.5-PEG-DTPA-Gd(III) hadsignificant enhanced R1 of 15.2 mM−1 s−1, higher than 4.3 mM−1 s−1 ofMagnevist. MRI imaging in vivo indicated that it had a much longercirculation time than Magnevist and significantly enhanced signal in thekidney.

References[1] S. Langereis, A. Dirksen, T.M. Hackeng, M.H.P. van Genderen, E.W. Meijer, Dendrimers and

magnetic resonance imaging, New J. Chem. 31 (2007) 1152–1160.[2] H. Kobayashi, M.W. Brechbiel, Dendrimer-based macromolecular MRI contrast agents:

characteristics and application, Mol. Imaging 2 (2003) 1–10.[3] A.R. Menjoge, R.M. Kannan, D.A. Tomalia, Dendrimer-based drug and imaging conjugates:

design considerations for nanomedical applications, Drug Discov. Today 15 (2010) 171–185.[4] J.C. Roberts, M.K. Bhalgat, R.T. Zera, Preliminary biological evaluation of polyamidoa-

mine (PAMAM) Starburst(TM) dendrimers, J. Biomed. Mater. Res. 30 (1996) 53–65.[5] X.P. Ma, J.B. Tang, Y.Q. Shen, M.H. Fan, H.D. Tang, M. Radosz, Facile synthesis of

polyester dendrimers from sequential click coupling of asymmetrical monomers, J. Am.Chem. Soc. 131 (2009) 14795–14803.

[6] H. Maeda, J. Fang, T. Inutsuka, Y. Kitamoto, Vascular permeability enhancement in solidtumor: various factors, mechanisms involved and its implications, Int. Immunopharma-col. 3 (2003) 319–328.

doi:10.1016/j.jconrel.2011.09.047

Effect of nano-structured polymer surfaces on osteoblastadhesion and proliferation

Soo-Jeong Yeon1, Jin-Wook Lee2, Jae-Won Lee1, Young-Je Kwark3,Seung Hyun Kim2, Kuen Yong Lee11Department of Bioengineering, Hanyang University, Seoul 133-791,Republic of Korea2Division of Nano-Systems Engineering, Inha University,Incheon 402-751, Republic of Korea

Abstracts / Journal of Controlled Release 152 (2011) e192–e269 e257

Scheme 1. Synthesis of dendritic MRI CA (G1.5-PEG-DTPA).

14 16 18

G0G1G2

Time (min)

G3

Fig. 1. Molecular-weight progress of the dendrimers with double bond end groups,measured by GPC.

Fig. 2. In vitro relaxivities of dendritic CA and Magnevist in water at 0.5 T and 32 °C.

Fig. 3. Whole body MR-imaging of mice injected with 0.033 mmol Gd/kg of G1.5-PEG-DTPA-Gd(III) (a) and Magnevist (b). The images were obtained within 20 min postinjection.

3Department of Organic Materials and Fiber Engineering,Soongsil University, Seoul 156-743, Republic of KoreaE-mail address: ysj2327@hotmail.com (S.-J. Yeon).

Abstract summaryControlling cell–matrix interactions in the nanometer size scale is

important for regulating cell phenotype in tissue engineering. Wehypothesized that adhesion and proliferation of osteoblasts could beinfluenced by varying the nano-structured surfaces. Poly(styrene-b-ethylene oxide) diblock copolymers were used to generate the nano-structured surfaces. As PS domain size decreased, cell proliferationwas enhanced. This approach to controlling cell phenotype by varyingthe surface structure in the nanometer size scale could be useful fordesigning novel scaffolds in tissue engineering applications.

Keywords: Cell–matrix interaction, Osteoblast, Nano-scale

IntroductionCell–matrix interactions regulate the shape and activity of the cell,

including migration, growth, and differentiation. Cells interact withextracellular matrices (ECMs) in many ways, often through aphenomenon known as contact guidance. Contact guidance ischaracterized by the response of cells to structures on the micro-and nanometer size scale [1]. Adhesion domains in synthetic ECMswith nano-scale structures significantly contribute to cell–matrixinteractions. In this study, we hypothesized that controlling thesurface structures of polymer matrices in the nanometer scale couldbe critical in regulation of osteoblast phenotype.

Experimental methodsPreparation of nano-structured surfaces. Poly(styrene-b-ethylene

oxide) (PS-b-PEO) diblock copolymers with different molecularweights and compositions were purchased from Polymer SourceInc. Dodecylbenzenesulfonic acid (DBSA) was used as an amphiphilicsurfactant exhibiting the molecular assembly [2]. PS-b-PEO and DBSAwere separately dissolved in benzene and then mixed together toform nano-structured surfaces and their structure was observed byAFM.

Cell culture. Mouse osteoblasts (MC3T3-E1) were seeded on nano-structured matrix at a density of 2.0×104 cells/mL, and were culturedin α-MEM supplemented with 10% FBS and 1% PS (37 °C, 5% CO2). Thenumber of cells was counted using a hemacytometer.

Results and discussionNano-structured surfaces were produced through self-assembly of

PS-b-PEO block copolymer/DBSA surfactant complex systems, andtheir structures were controlled by the composition and Mw ofcomponents (Fig. 1). In these patterned structure, PS domains had around shape and were considered cell adhesion sites.

We tested whether the difference in PS domain size (dPS) couldinfluence osteoblast adhesion and proliferation. MC3T3-E1 cells wereseeded on the surfaces with different PS domain sizes. We found thatthe cell growth was enhanced as dPS decreased, irrespective of thesame number of initially adhered cells. However, the aspect ratio ofadherent osteoblasts increased as dPS increased.

ConclusionVarious surfaces with well-defined and well-ordered domains

were prepared using PS-b-PEO block copolymer/DBSA surfactantcomplex systems. Adhesion and proliferation of osteoblasts werecontrolled by the surface nano-structures and the domain size was acritical parameter. This approach to controlling cellular adhesion andproliferation by varying the surface nano-structures could be usefulfor design of novel biomaterials for tissue engineering applications.

References[1] A.I. Teixeira, G.A. Abrams, P.J. Bertics, C.J. Murphy, P.F. Nealey, Epithelial contact guidance

on well-defined micro- and nanostructured substrates, Cell Sci. 116 (2003) 1881–1892.[2] J.W. Lee, C. Lee, S.Y. Choi, S.H. Kim, Block copolymer-surfactant complexes in thin

films for multiple usages from hierarchical structure to nano-objects, Macromolecules43 (2010) 442–447.

doi:10.1016/j.jconrel.2011.09.048

Active targeting and fluorescence-labeled micelles: Preparation,characterization and cellular uptake evaluation

Jun Yue1,2, Shi Liu1, Guojun Mo1,2, Rui Wang1,2, Xiabin Jing11State Key Laboratory of Polymer Physics and Chemistry,Changchun Institute of Applied Chemistry, Chinese Academy of Sciences,Changchun 130022, China2Graduate School of Chinese Academy of Sciences, Beijing 100049, ChinaE-mail address: yuejun@ciac.jl.cn (J. Yue).

Abstract summaryA novel amphipathic copolymer propargyl poly(ethylene glycol)-

b-poly(l-lactide) (propargyl-PEG-PLA) was synthesized successfully.By mixing with another amphipathic block copolymer poly(ethyleneglycol)-b-poly(l-lactide-co-2,2-dihydroxylmethyl-propylene carbo-nate/Rhodamine) [MPEG-P(LA-co-DHP/Rh)], fluorescence-labeledhybrid micelles were obtained. Transferrin as a targeting ligand wasimmobilized onto the surface of the hybrid micelles through the“click reaction”. The intracellular uptake of the hybrid micelles by

Abstracts / Journal of Controlled Release 152 (2011) e192–e269e258

Fig. 1. AFM images of (a) PS-b-PEO (40k/35k)/DBSA ([EO]/[DBSA]=0.5, dPS=58±5nm) and (b) PS-b-PEO (58.6k/31k)/DBSA ([EO]/[DBSA]=1.0, dPS=80±5 nm).

Fig. 2. Effect of domain size (dPS) on osteoblast proliferation (left bar, dPS=58±5 nm;right bar, dPS=80±5 nm).