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Docetaxel-loaded single-wall carbon nanohorns using anti-VEGF antibody as a targeting agent: characterization, in vitro and in vivo antitumor activity

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Abstract

A novel antitumor drug delivery system, docetaxel (DTX)-loaded oxidized single-wall carbon nanohorns (oxSWNHs) with anti-VEGF monoclonal antibody (mAb) as a target agent was constructed. DTX was absorbed onto the oxSWNHs via the physical adsorption or π–π interaction. DSPE–PEG–COOH was non-covalently wrapped to the hydrophobic surface of oxSWNHs to improve its water solubility and biocompatibility. The mAb was bonded to the PEG through amide bond. The DTX@oxSWNHs-PEG-mAb (DDS) exhibited suitable particle size (191.2 ± 2.1 nm), good particle size distribution (PDI: 0.196), and negative zeta potential (−24.3 ± 0.85 mV). These features enhanced permeability and retention (EPR) effect and reduced the drug molecule uptake by the reticuloendothelial system. The in vitro drug release followed non-Fickian diffusion (n = 0.6857, R = 0.9924) with the cumulative release of DTX 59 ± 1.35 % at 72 h. Compared with free DTX, the DDS enhanced the cytotoxicity in MCF-7 cell lines in vitro efficiently (IC50: 2.96 ± 0.6 μg/ml), and provided higher antitumor efficacy (TGI: 69.88 %) in vivo. The histological analysis indicated that the DDS had no significant side effect. Therefore, the new DDS is promising to attain higher pharmaceutical efficacy and lower side effects than free DTX for cancer therapy. The research demonstrated that DTX@oxSWNHs-PEG-mAb might have promising biomedical applications for future cancer therapy.

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Acknowledgments

The work was funded by the National Natural Science Foundation of China (No. 81173023) and supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). We wish to thank Professor Yu Liu, China Pharmaceutical University for their anti-VEGF monoclonal antibody. We appreciate Dr. Degang Fu for TEM measurements.

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Authors and Affiliations

  1. Department of Analytical Chemistry, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Qian Zhao, Nannan Li, Chang Shu, Ruixin Li, Xiaona Ma, Xuequan Li, Ran Wang & Wenying Zhong

  2. Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Wenying Zhong

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  1. Qian Zhao
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  2. Nannan Li
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  3. Chang Shu
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Correspondence to Wenying Zhong.

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Zhao, Q., Li, N., Shu, C. et al. Docetaxel-loaded single-wall carbon nanohorns using anti-VEGF antibody as a targeting agent: characterization, in vitro and in vivo antitumor activity. J Nanopart Res 17, 207 (2015). https://doi.org/10.1007/s11051-015-3015-4

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