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The drug loading behavior of PAMAM dendrimer: Insights from experimental and simulation study

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Abstract

Poly(amidoamine) (PAMAM) dendrimers are widely studied as drug vectors due to their particular structure and excellent properties. Drug molecules can be loaded in the internal cavity of dendrimers or adsorbed on the surface. In this paper, the interaction force and spatial configuration between PAMAM and several typical chemotherapy drugs (doxorubicin (DOX), paclitaxel (TAX), hydroxycamptothecin (HCPT)) is studied by molecular dynamics (MD) simulations. Several essential parameters of dendrimers as drug carriers are analyzed by combining experiments and MD simulations, including particle size, drug loading, drug release, and biocompatibility. The simulation of dendrimer@drug complexes demonstrates that many cavities are semi-open, and most drug molecules are not completely wrapped. The internal structure of PAMAM dendrimers became looser with more extended nuclei, which increased the non-covalent interactions between PAMAM dendrimers and drug molecules. The umbrella sampling simulations reveal that the change of binding energies between dendrimers and drug molecules is responsible for the variation in drug release rate. This study provides valuable enlightenment information for the drug loading/release of PAMAM dendrimers.

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References

  1. Lu Y, Slomberg D L, Shah A, et al. Nitric oxide-releasing amphiphilic poly(amidoamine) (PAMAM) dendrimers as antibacterial agents. Biomacromolecules, 2013, 14: 3589–3598

    Article  Google Scholar 

  2. Zhou L, Shan Y, Hu H, et al. Synthesis and biomedical applications of dendrimers. Curr Org Chem, 2018, 22: 600–612

    Article  Google Scholar 

  3. Cong H, Zhou L, Meng Q, et al. Preparation and evaluation of PA-MAM dendrimer-based polymer gels physically cross-linked by hydrogen bonding. Biomater Sci, 2019, 7: 3918–3925

    Article  Google Scholar 

  4. Maji S, Agarwal T, Maiti T K. PAMAM (generation 4) incorporated gelatin 3D matrix as an improved dermal substitute for skin tissue engineering. Colloids Surfs B-Biointerfaces, 2017, 155: 128–134

    Article  Google Scholar 

  5. Luong D, Kesharwani P, Deshmukh R, et al. PEGylated PAMAM dendrimers: Enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery. Acta Biomater, 2016, 43: 14–29

    Article  Google Scholar 

  6. Sun Y, Ma X, Jing X, et al. PAMAM-functionalized cellulose nano-crystals with needle-like morphology for effective cancer treatment. Nanomaterials, 2021, 11: 1640

    Article  Google Scholar 

  7. Sonuç Karaboğa M N, Sezgintürk M K. Determination of C-reactive protein by PAMAM decorated ITO based disposable biosensing system: A new immunosensor design from an old molecule. Talanta, 2018, 186: 162–168

    Article  Google Scholar 

  8. Sun Y, Hu H, Jing X, et al. Co-delivery of chemotherapeutic drugs and cell cycle regulatory agents using nanocarriers for cancer therapy. Sci China Mater, 2021, 64: 1827–1848

    Article  Google Scholar 

  9. Sun Y, Jing X, Ma X, et al. Versatile types of polysaccharide-based drug delivery systems: From strategic design to cancer therapy. Int J Mol Sci, 2020, 21: 9159

    Article  Google Scholar 

  10. Sun Q, Sun X, Ma X, et al. Integration of nanoassembly functions for an effective delivery cascade for cancer drugs. Adv Mater, 2014, 26: 7615–7621

    Article  Google Scholar 

  11. Xiong Z, Shen M, Shi X. Dendrimer-based strategies for cancer therapy: Recent advances and future perspectives. Sci China Mater, 2018, 61: 1387–1403

    Article  Google Scholar 

  12. Zou W T, Zhong W, Sun M G, et al. pH-Responsive dendrimer-functionalized cotton cellulose nanocrystals for effective cancer treatment. Ferroelectrics, 2021, 578: 108–112

    Article  Google Scholar 

  13. Wu J S, Li J X, Shu N, et al. A polyamidoamine (PAMAM) derivative dendrimer with high loading capacity of TLR7/8 agonist for improved cancer immunotherapy. Nano Res, 2022, 15: 510–518

    Article  Google Scholar 

  14. Pishavar E, Oroojalian F, Salmasi Z, et al. Recent advances of dendrimer in targeted delivery of drugs and genes to stem cells as cellular vehicles. Biotechnol Prog, 2021, 37: e3174

    Google Scholar 

  15. Ren L, Lv J, Wang H, et al. A coordinative dendrimer achieves excellent efficiency in cytosolic protein and peptide delivery. Angew Chem Int Ed, 2020, 59: 4711–4719

    Article  Google Scholar 

  16. Zhang C, Pan D, Luo K, et al. Dendrimer-doxorubicin conjugate as enzyme-sensitive and polymeric nanoscale drug delivery vehicle for ovarian cancer therapy. Polym Chem, 2014, 5: 5227–5235

    Article  Google Scholar 

  17. Tian W, Ma Y. Theoretical and computational studies of dendrimers as delivery vectors. Chem Soc Rev, 2013, 42: 705–727

    Article  Google Scholar 

  18. Sathe R Y, Bharatam P V. Drug-dendrimer complexes and conjugates: Detailed furtherance through theory and experiments. Adv Colloid Interface Sci, 2022, 303: 102639

    Article  Google Scholar 

  19. Tian F, Lin X, Valle R P, et al. Poly(amidoamine) dendrimer as a respiratory nanocarrier: Insights from experiments and molecular dynamics simulations. Langmuir, 2019, 35: 5364–5371

    Article  Google Scholar 

  20. Wang B, Sun Y, Davis T P, et al. Understanding effects of PAMAM dendrimer size and surface chemistry on serum protein binding with discrete molecular dynamics simulations. ACS Sustain Chem Eng, 2018, 6: 11704–11715

    Article  Google Scholar 

  21. Liu Y, Bryantsev V S, Diallo M S, et al. PAMAM dendrimers undergo pH responsive conformational changes without swelling. J Am Chem Soc, 2009, 131: 2798–2799

    Article  Google Scholar 

  22. Jafari M, Mehrnejad F, Talandashti R, et al. Effect of the lipid composition and cholesterol on the membrane selectivity of low generations PAMAM dendrimers: A molecular dynamics simulation study. Appl Surf Sci, 2021, 540: 148274

    Article  Google Scholar 

  23. Maingi V, Kumar M V S, Maiti P K. PAMAM dendrimer-drug interactions: Effect of pH on the binding and release pattern. J Phys Chem B, 2012, 116: 4370–4376

    Article  Google Scholar 

  24. Jain V, Maiti P K, Bharatam P V. Atomic level insights into realistic molecular models of dendrimer-drug complexes through MD simulations. J Chem Phys, 2016, 145: 124902

    Article  Google Scholar 

  25. Jing X, Sun Y, Liu Y, et al. Alginate/chitosan-based hydrogel loaded with gene vectors to deliver polydeoxyribonucleotide for effective wound healing. Biomater Sci, 2021, 9: 5533–5541

    Article  Google Scholar 

  26. Raemdonck K, Demeester J, de Smedt S. Advanced nanogel engineering for drug delivery. Soft Matter, 2009, 5: 707–715

    Article  Google Scholar 

  27. Van Der Spoel D, Lindahl E, Hess B, et al. GROMACS: Fast, flexible, and free. J Comput Chem, 2005, 26: 1701–1718

    Article  Google Scholar 

  28. Martínez L, Andrade R, Birgin E G, et al. PACKMOL: A package for building initial configurations for molecular dynamics simulations. J Comput Chem, 2009, 30: 2157–2164

    Article  Google Scholar 

  29. Kästner J. Umbrella sampling. WIREs Comput Mol Sci, 2011, 1: 932–942

    Article  Google Scholar 

  30. Gao W, Jiao Y, Dai L L. The effects of size, shape, and surface composition on the diffusive behaviors of nanoparticles at/across water-oil interfaces via molecular dynamics simulations. J Nanopart Res, 2016, 18: 91

    Article  Google Scholar 

  31. Barra P A, Barraza L, Jiménez V A, et al. Complexation of mefenamic acid by low-generation PAMAM dendrimers: Insight from NMR spectroscopy studies and molecular dynamics simulations. Macromol Chem Phys, 2014, 215: 372–383

    Article  Google Scholar 

  32. Hu J, Xu T, Cheng Y. NMR insights into dendrimer-based host-guest systems. Chem Rev, 2012, 112: 3856–3891

    Article  Google Scholar 

  33. Meng Q, Hu H, Zhou L, et al. Logical design and application of prodrug platforms. Polym Chem, 2019, 10: 306–324

    Article  Google Scholar 

  34. Marzinek J K, Bond P J, Lian G, et al. Free energy predictions of ligand binding to an α-helix using steered molecular dynamics and umbrella sampling simulations. J Chem Inf Model, 2014, 54: 2093–2104

    Article  Google Scholar 

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Biomedical Materials and Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao, 266071, China

    LiPing Zhou, Bing Yu, Hao Hu, HaiLin Cong & YouQing Shen

  2. State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University, Qingdao, 266071, China

    LiPing Zhou, Bing Yu & HaiLin Cong

  3. Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 100083, China

    LiPing Zhou

  4. School of Materials Science and Engineering, China University of Petroleum, Qingdao, 266580, China

    JiaWei Li & Jun Zhang

  5. Center for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, China

    YouQing Shen

Authors
  1. LiPing Zhou
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  2. JiaWei Li
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  4. Jun Zhang
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Corresponding authors

Correspondence to Jun Zhang, Hao Hu or HaiLin Cong.

Additional information

This work was supported by the National Natural Science Foundation of China (Grant Nos. 21874078, 22074072, and 22274083), the Taishan Young Scholar Program of Shandong Province (Grant No. tsqn20161027), the China Postdoctoral Science Foundation (Grant No. 2018M630752), the Postdoctoral Scientific Research Foundation of Qingdao, the Innovation and Development Joint Fund of Natural Science Foundation of Shandong Province (Grant No. ZR2022LZY022), the Science and Technology Planing Project of South District of Qingdao City (Grant No. 2022-4-005-YY), the Exploration Project of the State Key Laboratory of BioFibers and Eco-Textiles of Qingdao University (Grant No. TSKT202101), and the High Level Discipline Project of Shandong Province.

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The supporting information is available online at tech.scichina.com and link.springer.com. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Zhou, L., Li, J., Yu, B. et al. The drug loading behavior of PAMAM dendrimer: Insights from experimental and simulation study. Sci. China Technol. Sci. 66, 1129–1140 (2023). https://doi.org/10.1007/s11431-022-2178-8

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  • DOI: https://doi.org/10.1007/s11431-022-2178-8

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