copolymerized in the presence of alginic acid (ALG-H) in aqueoussolutions without any organic solvents or surfactants, yielding stablecomplex micelles in one-pot.

Transmission electron microscopy (TEM) and particle sizeanalyses have shown that stable micelles with an average diameterof 120 nm and narrowed distribution are formed. The ζ potential isnegative (around −60 mV), indicating that the outer shell of themicelle partly consists of alginate which has not been complexed.The drug doxorubicin is conjugated with the micelles with a highloading efficiency through the formation of hydrazone bonds withDAA structural units. The drug is released under acidic conditions.The micelles exhibit many advantages such as simple preparationwithout organic solvents or surfactants, low cost, biocompatible,non-cytotoxic and pH controlled release.

Scheme 1. (a) The doxorubicin-conjugated micelle of poly[(2-dimethylamino) ethylmethacrylate-co-diacetone acrylamide] and alginic acid; (b) the drug release profile.

Keywords: Polyion, Complex micelle, Doxorubicin, Alginate,pH-controlled release

AcknowledgmentsThis work was supported by the State Key Laboratory of

Hydrology-Water Resources and Hydraulic Engineering, HohaiUniversity (No: 2010490911).

References[1] A. Boudier, A. Aubert-Pouëssel, N. Mebarek, A. Chavanieu, J. Quentin, D.

Martire, Development of tripartite polyion micelles for efficient peptide deliveryinto dendritic cells without altering their plasticity, J. Control. Release 154 (2011)156–163.

[2] Y. Luo, A. Wang, J. Yuan, Q. Gao, Preparation, characterization and drug releasebehavior of polyion complex micelles, Int. J. Pharm. 374 (2009) 139–144.

doi:10.1016/j.jconrel.2013.08.042

Polymer–lipid hybrid nanoparticles with reduction-triggeredrelease for improved antitumor efficiency

Can Cui, Ya-Nan Xue, Ming Wu, Yang Zhang, Ping Yu,Ren-Xi Zhuo, Shi-Wen Huang⁎

Key Laboratory of Biomedical Polymers of Ministry of Education,Department of Chemistry, Wuhan University, Wuhan 430072, ChinaE-mail addresses: ccals@163.com (C. Cui),swhuang@whu.edu.cn (S.-W. Huang).

Polymer–lipid hybrid nanoparticles (PLNPs) are importantnanocarriers for chemotherapeutic delivery, which combine the desirablecharacteristics of polymericNPs and liposomes, prevent the carried agentsfrom free diffusion out of the PLNPs and reduce thewater penetration rateinto the PLNPs, thereby enhancing the drug encapsulation yield and slowdrug release from the PLNPs [1]. However, fast release of encapsulatedanticancer drugs into targeted tumor cells is crucial for enhancing the

pharmaceutical effect. In the past decade, reduction-sensitive nano-carriers have received more attention for the fast delivery of antitumordrugs due to the significant difference of the concentration of reducingagents between the extracellular milieu and intracellular fluid.

Here, reduction-sensitive PLNPs consisting of (I) poly(D,L-lactide-co-glycolide) hydrophobic core, (II) soybean lecithin monolayer, and(III) amphiphilic polymer mPEG-S-S-C16 composed of a C16 alkylgroup and mPEG for providing a sheddable PEG shell, were preparedand evaluated for anticancer drug delivery. Reduction-insensitivePLNPs with analogical structure were also prepared as control.The obtained DOX-loaded reduction-sensitive PLNPs with an averagesize of about 92 nm were loaded with DOX with a content of 3.8%.In vitro release revealed that, in the presence of dithiothreitol(DTT), DOX-loaded reduction-sensitive PLNPs released DOX fasterthan DOX-loaded reduction-insensitive PLNPs, whereas they showeda similar release rate in the absence of DTT. MTT assay demonstratedsignificantly enhanced cytotoxicity of DOX-loaded reduction-sensi-tive PLNPs against HeLa cells compared with DOX-loaded reduction-insensitive PLNPs. CLSM showed that DOX-loaded reduction-sensi-tive PLNPs were efficiently internalized into HeLa cells and releasedDOX into the cytoplasm, which entered the nuclei. In contrast,in the case of DOX-loaded reduction-insensitive PLNPs, only a littleDOX was found in the nucleus. Endocytosis inhibition resultsindicated that DOX-loaded reduction-sensitive PLNPs entered cellsprominently via clathrin-mediated endocytosis. The results demon-strated that reduction-sensitive PLNPs showed more effective intra-cellular delivery of anticancer drug into tumor cells than reduction-insensitive PLNPs.

Fig. 1. (A) Cytotoxicity of DOX-loaded PLNPs and free DOX in HeLa cells after incubationfor 48 h and (B) CLSM images of HeLa cells after treatment with DOX-loaded reduction-sensitive PLNPs (a) and DOX-loaded reduction-insensitive PLNPs (b) for 24 h.

Keywords: Polymer–lipid, Hybrid nanoparticle, Reduction-sensitive,Drug delivery

AcknowledgmentsThis workwas supported by the National Natural Science Foundation

of China (21074101) and National Basic Research Program of China(2009CB930300).

Reference[1] Y.T. Liu, K. Li, J. Pan, B. Liu, S.S. Feng, Folic acid conjugated nanoparticles of

mixed lipid monolayer shell and biodegradable polymer core for targeted deliveryof docetaxel, Biomaterials 31 (2010) 330–338.

doi:10.1016/j.jconrel.2013.08.043

A one-step green chemical route to fabricate photoluminescentcarbon dots with great potential application in bioimaging

Changjun Liua,b, Fan Lia, Peng Zhangb, Xinyun Zhaib, Jian Yanga,Yuan Liub, Feng Tiana

aInstitute of Medical Equipment, Academy of Military Medical Science,Tianjin 300161, China

Abstracts / Journal of Controlled Release 172 (2013) e14–e97 e17

bSchool of Materials Science and Engineering, Tianjin Key Laboratoryof Composite and Functional Materials, Tianjin University,Tianjin 300072, ChinaE-mail addresses: hunterlcj@163.com (C. Liu),tianfeng62037@yahoo.com.cn (F. Tian).

Since reported firstly by Sun and his coworkers at 2006 [1],carbon dots have excited tremendous research interest owing totheir remarkable advantages in stable photoluminescence (PL),broad excitation spectra, tunable emission wavelength and excellentbiocompatibility compared with conventional organic dyes andsemiconductor quantum dots. Therefore, carbon dots are a promisingcandidate in many fields of technologies such as gene/drug delivery[2], bioimaging [3], photocatalysts, sensors and diagnostics. Herein,strong fluorescent carbon dots were prepared on a large scale bymicrowave assisted pyrolysis of D-Glucosamine hydrochloride solu-tion in minutes. For this absolutely green strategy, the mostfavorable feature was that neither an acid solvent nor diamine-terminated surface passivation agent was needed. The synthesizedcarbon dots exhibited very low cytotoxicity, excellent watersolubility and multicolor photoluminescent properties. For laserconfocal microscopy observation, the carbon dots treated COS-7cells became quite bright, showing blue, green and red color,respectively, under 405 nm, 488 nm and 543 nm excitation wave-lengths, revealing that the carbon dots had been internalized into thecells. Owing to its multicolor luminescence, carbon dots endow usersmuch freedom to choose the excitation wavelength for observation,which is a great advantage over other labeling agents.

Fig. 1. Schematic illustration of the fabrication of carbon dots (a); laser scanningconfocal microscopy images of carbon dots treated COS-7 cells (b, scale bars:40 μm).

Keywords: Carbon dots, Photoluminescence, Bioimaging, Microwave

AcknowledgmentsThe authors gratefully acknowledge the support for this work

from the National Science and Technology Major Project of China(Grant 2012ZX10004801-003).

References[1] Y.P. Sun, B. Zhou, Y. Lin, W. Wang, K.A.S. Fernando, P. Pathak, M.J. Meziani, B.A.

Harruff, X. Wang, H. Wang, P.G. Luo, H. Yang, M.E. Kose, B. Chen, L.M. Veca,S.Y. Xie, Quantum-sized carbon dots for bright and colorful photoluminescence,J. Am. Chem. Soc. 128 (2006) 7756–7757.

[2] C.J. Liu, P. Zhang, X.Y. Zhai, F. Tian, W.C. Li, J.H. Yang, Y. Liu, H.B. Wang, W.Wang, W.G. Liu, Nano-carrier for gene delivery and bioimaging based on carbondots with PEI-passivation enhanced fluorescence, Biomaterials 33 (2012)3604–3613.

[3] C.J. Liu, P. Zhang, F. Tian, W.C. Li, F. Li, W.G. Liu, One-step synthesis of surfacepassivated carbon nanodots by microwave assisted pyrolysis for enhancedmulticolor photoluminescence and bioimaging, J. Mater. Chem. 21 (2011)13163–13171.

doi:10.1016/j.jconrel.2013.08.044

Application of aqueous silicone–acrylate emulsions in coatedcontrolled release fertilizer

Changwen Du, Yazhen Shen, Jianmin ZhouState Key Laboratory of Soil and Sustainable Agriculture, Institute of SoilScience Chinese Academy of Sciences, Nanjing 210008, ChinaE-mail address: chwdu@issas.ac.cn (C. Du).

Hydrophobic polymer coated fertilizers are the major categories ofcontrolled release fertilizer (CRF) as they have excellent nutrient releaseprofiles [1]. Water-borne coating techniques have been mainly studiedbecause of strict pollution regulations. Aqueous based coatings candecrease coating costs and avoid possible secondary pollution resultingfrom volatile organic solvent based coatings [2]. The objectives of thisstudy were to synthesize water-borne silicone–acrylate emulsions forcoated CRF. The waterborne acrylate emulsions modified by differentorganic silicones (n-butyl acrylate (BA),methylmethacrylate (MMA) andvinyltriethoxysilane (VTES))were synthesized to develop coated CRF, andthe influences of monomer ratio on the coating properties and nutrientrelease profiles were investigated. Silicone–acrylate emulsions usingdifferent BA/MMAratios of 110:90, 100:100 and90:110werepreparedbymini-emulsion polymerization, which were denoted by S1, S2 and S3,respectively. The synthesized silicone–acrylate emulsions were used todevelop coated CRF with fluidized bed. Fourier transform photoacousticspectroscopy (FTIR-PAS) was employed to characterize the coatings, andthe nutrient's release profiles were determined. The wide and strong OHabsorption at 3250–3750 cm−1 showed a lower intensity in S3 than in S1and S2, which resulted from higher monomer reactivity ratios of MMA.The band in the range of 990–1130 cm−1 was broad and strong becauseof the SiOSi asymmetric stretching,which indicated that VTESwas graftedonto the acrylate chain. The absorption band appearing at 1640 cm−1 inthe spectrum, which corresponded to the CC vibration, was very weakcompared to the strong CO vibration at 1740 cm−1, and this suggests thatCC in VTES had been well reacted with acrylate. For silicone–acrylateemulsions with different BA/MMA ratios, the nutrient release durationswere in the order of S1 N S2 N S3 (Fig. 1), and S1 coated CRF just deliveredabout 20% of the total nutrients (NPK) in 30 days. Therefore, the waterborne silicone–acrylate emulsions were successfully synthesized withexcellent performance of nutrient controlled release, which providednovel and improved materials for coated CRF industry.

Keywords: Coated fertilizer, Aqueous emulsion, Release profile,Photoacoustic spectroscopy

AcknowledgmentsThis work was supported by the national R&D project in “the

Twelfth Five Year” (2011BAD11B01-02) and the cooperation projectbetween Chinese Academy of Sciences and local industry.

Fig. 1. Characterization of water borne coatings: effects on nutrient release.

Abstracts / Journal of Controlled Release 172 (2013) e14–e97e18