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Binding and conformation of dendrimer-based drug delivery systems: a molecular dynamics study

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Abstract

All atomistic molecular dynamics simulations were performed on poly (amidoamine) (PAMAM) dendrimers that compound non-covalently with anticancer drug molecules including DOX, MTX, CE6, and SN38. The binding energies as well as their associated interaction energies and deformation energies were combined to evaluate the relative binding strength among drug, PAMAM, and PEG chains. We find that the deformation of dendrimers due to drug loading plays a crucial role in the drug binding. It is energetically favorable for the drug molecules to bind with PAMAM while the drugs bind with PEG metastable chains via kinetic confinement. Surface PEGylation helps dendrimers to accommodate more drug molecules with greater strength without inducing too much expansion. This work indicates that tuning the functionalized terminal groups of dendrimers is critical to design efficient dendrimer-based drug delivery systems.

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Acknowledgments

The authors are grateful for financial supports from “Shanghai Pujiang Talent” program (Grant No. 12PJ1406500), “Shanghai High-tech Area of Innovative Science and Technology (Grant No. 14521100602)”, STCSM; “Key Program of Innovative Scientific Research” (Grant No. 14ZZ130) and “Key Laboratory of Advanced Metal-based Electrical Power Materials”, the Education Commission of Shanghai Municipality; State Key Laboratory of Heavy Oil Processing, China University of Petroleum (Grant No. SKLOP201402001); National Natural Science Foundation of China (Grant Nos. 51202137, 61240054, and 11274222). Computations were carried out at Hujiang HPC facilities at USST, Shanghai Supercomputer Center, and National Supercomputing Center in Shenzhen, P.R. China.

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Authors and Affiliations

  1. Department of Physics and Materials Genome Institute, Shanghai University, Shanghai, 200444, P. R. China

    Fa-Da Zhang, Yi Liu & Xin-Luo Zhao

  2. School of Materials Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, P. R. China

    Fa-Da Zhang, Yi Liu, Jing-Cheng Xu, Sheng-Juan Li, Xiu-Nan Wang & Yue Sun

  3. School of Energy & Power Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, P. R. China

    Fa-Da Zhang & Xiu-Nan Wang

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  1. Fa-Da Zhang
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Correspondence to Yi Liu or Jing-Cheng Xu.

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Zhang, FD., Liu, Y., Xu, JC. et al. Binding and conformation of dendrimer-based drug delivery systems: a molecular dynamics study. Adv. Manuf. 3, 221–231 (2015). https://doi.org/10.1007/s40436-015-0120-7

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  • DOI: https://doi.org/10.1007/s40436-015-0120-7

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