Binding and conformation of dendrimer-based drug delivery systems: a molecular dynamics study
Source abstract
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.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Dendrimers and Hyperbranched Polymers · RNA Interference and Gene Delivery · Chemical Synthesis and Analysis
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (36)
Show source-provided references
1. Menjoge AR, Kannan RM, Tomalia DA (2010) Dendrimer-based drug and imaging conjugates: design considerations for nanomedical applications. Drug Discov Today 15(5):171–18510.1016/j.drudis.2010.01.009 ↗
2. Tomalia DA, Baker H, Dewald J et al (1985) A new class of polymers: starburst-dendritic macromolecules. Polym J 17(1):117–13210.1295/polymj.17.117 ↗
3. Kolhe P, Misra E, Kannan RM et al (2003) Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers. Int J Pharm 259(1):143–16010.1016/S0378-5173(03)00225-4 ↗
4. Zhang YH, Thomas TP, Lee KH et al (2011) Polyvalent saccharide-functionalized generation 3 poly(amidoamine) dendrimer–methotrexate conjugate as a potential anticancer agent. Bioorgan Med Chem 19(8):2557–256410.1016/j.bmc.2011.03.019 ↗
5. Kurtoglu YE, Mishra MK, Kannan S et al (2010) Drug release characteristics of PAMAM dendrimer–drug conjugates with different linkers. Int J Pharm 384(1):189–19410.1016/j.ijpharm.2009.10.017 ↗
6. Wiener EC, Brechbiel MW, Brothers H et al (1994) Dendrimer-based metal-chelates: a new class of magnetic resonance imaging contrast agents. Magn Reson Med 31(1):1–810.1002/mrm.1910310102 ↗
7. Kobayashi H, Saga T, Kawamoto S et al (2001) Dynamic micro-magnetic resonance imaging of liver micrometastasis in mice with a novel liver macromolecular magnetic resonance contrast agent DAB-Am64-(1B4M-Gd) 64. Cancer Res 61(13):4966–4970
8. Majoros IJ, Williams CR, Baker JR (2008) Current dendrimer applications in cancer diagnosis and therapy. Curr Top Med Chem 8(14):1165–117910.2174/156802608785849049 ↗
9. Lee CC, MacKay JA, Frechet JMJ et al (2005) Designing dendrimers for biological applications. Nat Biotechnol 23(12):1517–152610.1038/nbt1171 ↗
10. Esfand R, Tomalia DA (2001) Poly (amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. Drug Discov Today 6(8):427–43610.1016/S1359-6446(01)01757-3 ↗
11. Kavyani S, Amjad-Iranagh S, Modarress H (2014) Aqueous poly(amidoamine) dendrimer G3 and G4 generations with several interior cores at pHs 5 and 7: a molecular dynamics simulation study. J Phys Chem B 118(12):3257–326610.1021/jp409195c ↗
12. Mignani S, El Kazzouli S, Bousmina M et al (2013) Expand classical drug administration ways by emerging routes using dendrimer drug delivery systems: a concise overview. Adv Drug Deliv Rev 65(10):1316–133010.1016/j.addr.2013.01.001 ↗
13. Svenson S, Tomalia DA (2012) Dendrimers in biomedical applications—reflections on the field. Adv Drug Deliv Rev 64(1):102–10510.1016/j.addr.2012.09.030 ↗
14. Tomalia DA, Naylor AM, Goddard WA (1990) Starburst dendrimers: molecular-level control of size, shape, surface chemistry, topology and flexibility from atoms to macroscopic matter. Angew Chem Int Edit 29(2):138–17510.1002/anie.199001381 ↗
15. Yabbarov NG, Posypanova GA, Vorontsov EA et al (2013) Targeted delivery of doxorubicin: drug delivery system based on PAMAM dendrimers. Biochemistry (Moscow) 78(8):884–89410.1134/S000629791308004X ↗
16. Chang YL, Liu N, Chen L et al (2012) Synthesis and characterization of DOX-conjugated dendrimer-modified magnetic iron oxide conjugates for magnetic resonance imaging, targeting, and drug delivery. J Mater Chem 22(19):9594–960110.1039/c2jm16792a ↗
17. Wang Y, Cao XY, Guo R et al (2011) Targeted delivery of doxorubicin into cancer cells using a folic acid–dendrimer conjugate. Polym Chem 2(8):1754–176010.1039/c1py00179e ↗
18. Chang YL, Li YP, Meng XL et al (2013) Dendrimer functionalized water soluble magnetic iron oxide conjugates as dual imaging probe for tumor targeting and drug delivery. Polym Chem 4(3):789–79410.1039/C2PY20740K ↗
19. Majoros IJ, Myc A, Thomas T et al (2006) PAMAM dendrimer-based multifunctional conjugate for cancer therapy: synthesis, characterization, and functionality. Biomacromolecules 7(2):572–57910.1021/bm0506142 ↗
20. Rekas A, Lo V, Gadd GE et al (2009) PAMAM dendrimers as potential agents against fibrillation of alpha-synuclein, a Parkinson’s disease-related protein. Macromol Biosci 9(3):230–23810.1002/mabi.200800242 ↗
21. Kang H, DeLong R, Fisher MH et al (2005) Tat-conjugated PAMAM dendrimers as delivery agents for antisense and siRNA oligonucleotides. Pharm Res 22(12):2099–210610.1007/s11095-005-8330-5 ↗
22. Majoros IJ, Thomas TP, Mehta CB et al (2005) Poly(amidoamine) dendrimer-based multifunctional engineered nanodevice for cancer therapy. J Med Chem 48(19):5892–589910.1021/jm0401863 ↗
23. Wang W, Xiong W, Zhu YH et al (2010) Protective effect of PEGylation against poly(amidoamine) dendrimer-induced hemolysis of human red blood cells. J Biomed Mater Res B 93B(1):59–6410.1002/jbm.b.31558 ↗
24. He H, Li Y, Jia XR et al (2011) PEGylated poly(amidoamine) dendrimer-based dual-targeting carrier for treating brain tumors. Biomaterials 32(2):478–48710.1016/j.biomaterials.2010.09.002 ↗
25. Sideratou Z, Kontoyianni C, Drossopoulou GI et al (2010) Synthesis of a folate functionalized PEGylated poly(propylene imine) dendrimer as prospective targeted drug delivery system. Bioorg Med Chem Lett 20(22):6513–651710.1016/j.bmcl.2010.09.058 ↗
26. Singh P, Gupta U, Asthana A et al (2008) Folate and folate-PEG-PAMAM dendrimers: synthesis, characterization, and targeted anticancer drug delivery potential in tumor bearing mice. Bioconjug Chem 19(11):2239–225210.1021/bc800125u ↗
27. Isakau HA, Parkhats MV, Knyukshto VN et al (2008) Toward understanding the high PDT efficacy of chlorine6–polyvinylpyrrolidone formulations: photophysical and molecular aspects of photosensitizer–polymer interaction in vitro. J Photochem Photobiol B 92(3):165–17410.1016/j.jphotobiol.2008.06.004 ↗
28. Goldberg DS, Vijayalakshmi N, Swaan PW et al (2011) G3.5 PAMAM dendrimers enhance transepithelial transport of SN38 while minimizing gastrointestinal toxicity. J Control Release 150(3):318–32510.1016/j.jconrel.2010.11.022 ↗
29. Allen TM, Cullis PR (2004) Drug delivery systems: entering the mainstream. Science 303(5665):1818–182210.1126/science.1095833 ↗
30. Tian WD, Ma YQ (2012) pH-responsive dendrimers interacting with lipid membranes. Soft Matter 8(9):2627–263210.1039/c2sm06624f ↗
31. Maingi V, Kumar MVS, Maiti PK (2012) PAMAM dendrimer−drug interactions: effect of pH on the binding and release pattern. J Phys Chem B 116(14):4370–437610.1021/jp211515g ↗
32. Crampton HL, Simanek EE (2007) Dendrmers as drug delivery vehicles: non-covalent interactions of bioactive compounds with dendrimers. Polym Int 56(4):489–49610.1002/pi.2230 ↗
33. Kwon IK, Lee SC, Han B et al (2012) Analysis on the current status of targeted drug delivery to tumors. J Control Release 164(2):108–11410.1016/j.jconrel.2012.07.010 ↗
34. Karatasos K, Krystallis M (2009) Dynamics of counterions in dendrimer polyelectrolyte solutions. J Chem Phys 130(11):1–1110.1063/1.3088849 ↗
35. Zhong TP, Ai PF, Zhou J (2011) Structures and properties of PAMAM dendrimer: a multi-scale simulation study. Fluid Phase Equilib 302(1):43–4710.1016/j.fluid.2010.09.037 ↗
36. Liu Y, Bryantsev VS, Diallo MS et al (2009) PAMAM dendrimers undergo pH responsive conformational changes without swelling. J Am Chem Soc 131(8):2798–279910.1021/ja8100227 ↗