Molecular dynamics insight into drug-loading capacity of dodecylphosphocholine aggregate for doxorubicin
Abstract
The therapeutic effect of doxorubicin (DOX) on various cancers is enticing, but its huge toxic side effects are equally obvious. Loading it into nanocarriers and then delivering the drug is currently the most promising solution. In this work, we investigate the assembly mechanism of dodecylphosphorylcholine (DPC) aggregates for encapsulating DOXs using molecular dynamics simulation with an all-atomic force field. The principal propellants of the drug encapsulation procedure encompass hydrophobic and van der Waals interactions. Additionally, hydrogen bonding and electrostatic interactions wield significant influence in the aggregation dynamics of DPCs. The radial distribution function indicates that when DPC aggregates act as stable carriers exerting strong adhesion to the drugs, intermolecular interactions predominantly manifest within the spatial interval ranging from 0.5 nm to 1.0 nm. All calculated data and visualized images of the system configuration changing with simulation time reveal that after about 30 ns, the changes in DPC aggregation sites tend to ultimately form multiple aggregates and exhibit a good morphology loaded with DOXs. Our study explored the drug-carrying potential of DPC, which provides an important theoretical basis and effective guidance for researchers to design a more suitable DDS for DOX and then break through the bottleneck of the clinical application of DOX.
References
Wang Q, Jiang F, Zhao C, et al. miR-21-5p prevents doxorubicin-induced cardiomyopathy by downregulating BTG2. Heliyon. 2023; 9(5): e15451. doi: 10.1016/j.heliyon.2023.e15451
Abd-Elmoneim OM, Abd El-Rahim AH, Hafiz NA. Evaluation of selenium nanoparticles and doxorubicin effect against hepatocellular carcinoma rat model cytogenetic toxicity and DNA damage. Toxicology Reports. 2018; 5: 771-776. doi: 10.1016/j.toxrep.2018.07.003
dos Santos JM, Alfredo TM, Antunes KÁ, et al. Guazuma ulmifolia Lam. Decreases Oxidative Stress in Blood Cells and Prevents Doxorubicin-Induced Cardiotoxicity. Oxidative Medicine and Cellular Longevity. 2018; 2018: 1-16. doi: 10.1155/2018/2935051
Jabłońska-Trypuć A, Świderski G, Krętowski R, et al. Newly Synthesized Doxorubicin Complexes with Selected Metals—Synthesis, Structure and Anti-Breast Cancer Activity. Molecules. 2017; 22(7): 1106. doi: 10.3390/molecules22071106
Zhang W, Taheri-Ledari R, Ganjali F, et al. Nanoscale bioconjugates: A review of the structural attributes of drug-loaded nanocarrier conjugates for selective cancer therapy. Heliyon. 2022; 8(6): e09577. doi: 10.1016/j.heliyon.2022.e09577
Kondiah PPD, Choonara YE, Kondiah PJ, et al. Nanocomposites for therapeutic application in multiple sclerosis. In: Applications of Nanocomposite Materials in Drug Delivery. Woodhead Publishing; 2018; pp. 391-408.
Masina N, Choonara YE, Kumar P, et al. A review of the chemical modification techniques of starch. Carbohydrate Polymers. 2017; 157: 1226-1236. doi: 10.1016/j.carbpol.2016.09.094
Niu W, Xiao Q, Wang X, et al. A Biomimetic Drug Delivery System by Integrating Grapefruit Extracellular Vesicles and Doxorubicin-Loaded Heparin-Based Nanoparticles for Glioma Therapy. Nano Letters. 2021; 21(3): 1484-1492. doi: 10.1021/acs.nanolett.0c04753
Mdlovu NV, Lin KS, Weng MT, et al. Design of doxorubicin encapsulated pH-/thermo-responsive and cationic shell-crosslinked magnetic drug delivery system. Colloids and Surfaces B: Biointerfaces. 2022; 209: 112168. doi: 10.1016/j.colsurfb.2021.112168
Darson J, Thirunellai Seshadri R, Katariya K, et al. Design development and optimisation of multifunctional Doxorubicin-loaded Indocynanine Green proniosomal gel derived niosomes for tumour management. Scientific Reports. 2023; 13(1). doi: 10.1038/s41598-023-28891-8
Mohanty A, Uthaman S, Park IK. Utilization of Polymer-Lipid Hybrid Nanoparticles for Targeted Anti-Cancer Therapy. Molecules. 2020; 25(19): 4377. doi: 10.3390/molecules25194377
Faramarzi S, Bonnett B, Scaggs CA, et al. Molecular Dynamics Simulations as a Tool for Accurate Determination of Surfactant Micelle Properties. Langmuir. 2017; 33(38): 9934-9943. doi: 10.1021/acs.langmuir.7b02666
Harris JJ, Pantelopulos GA, Straub JE. Finite-Size Effects and Optimal System Sizes in Simulations of Surfactant Micelle Self-Assembly. The Journal of Physical Chemistry B. 2021; 125(19): 5068-5077. doi: 10.1021/acs.jpcb.1c01186
Siebert HC, Eckert T, Bhunia A, et al. Blood pH Analysis in Combination with Molecular Medical Tools in Relation to COVID-19 Symptoms. Biomedicines. 2023; 11(5): 1421. doi: 10.3390/biomedicines11051421
Saravanan R, Bhattacharjya S. Oligomeric structure of a cathelicidin antimicrobial peptide in dodecylphosphocholine micelle determined by NMR spectroscopy. Biochimica et Biophysica Acta (BBA)—Biomembranes. 2011; 1808(1): 369-381. doi: 10.1016/j.bbamem.2010.10.001
Serra-Batiste M, Ninot-Pedrosa M, Bayoumi M, et al. Aβ42 assembles into specific β-barrel pore-forming oligomers in membrane-mimicking environments. Proceedings of the National Academy of Sciences. 2016; 113(39): 10866-10871. doi: 10.1073/pnas.1605104113
Ganapathy S, Opdam L, Hontani Y, et al. Membrane matters: The impact of a nanodisc-bilayer or a detergent microenvironment on the properties of two eubacterial rhodopsins. Biochimica et Biophysica Acta (BBA)—Biomembranes. 2020; 1862(2): 183113. doi: 10.1016/j.bbamem.2019.183113
Izadyar A, Farhadian N, Chenarani N. Molecular dynamics simulation of doxorubicin adsorption on a bundle of functionalized CNT. Journal of Biomolecular Structure and Dynamics. 2015; 34(8): 1797-1805. doi: 10.1080/07391102.2015.1092475
Mirhosseini MM, Rahmati M, Zargarian SS, et al. Molecular dynamics simulation of functionalized graphene surface for high efficient loading of doxorubicin. Journal of Molecular Structure. 2017; 1141: 441-450. doi: 10.1016/j.molstruc.2017.04.007
Karnati KR, Wang Y. Understanding the co-loading and releasing of doxorubicin and paclitaxel using chitosan functionalized single-walled carbon nanotubes by molecular dynamics simulations. Physical Chemistry Chemical Physics. 2018; 20(14): 9389-9400. doi: 10.1039/c8cp00124c
Kordzadeh A, Amjad-Iranagh S, Zarif M, et al. Adsorption and encapsulation of the drug doxorubicin on covalent functionalized carbon nanotubes: A scrutinized study by using molecular dynamics simulation and quantum mechanics calculation. Journal of Molecular Graphics and Modelling. 2019; 88: 11-22. doi: 10.1016/j.jmgm.2018.12.009
Pakdel M, Raissi H, Shahabi M. Predicting doxorubicin drug delivery by single-walled carbon nanotube through cell membrane in the absence and presence of nicotine molecules: a molecular dynamics simulation study. Journal of Biomolecular Structure and Dynamics. 2019; 38(5): 1488-1498. doi: 10.1080/07391102.2019.1611474
Shirazi-Fard S, Mohammadpour F, Zolghadr AR, et al. Encapsulation and Release of Doxorubicin from TiO2Nanotubes: Experiment, Density Functional Theory Calculations, and Molecular Dynamics Simulation. The Journal of Physical Chemistry B. 2021; 125(21): 5549-5558. doi: 10.1021/acs.jpcb.1c02648
Maleki R, Afrouzi HH, Hosseini M, et al. Molecular dynamics simulation of Doxorubicin loading with N-isopropyl acrylamide carbon nanotube in a drug delivery system. Computer Methods and Programs in Biomedicine. 2020; 184: 105303. doi: 10.1016/j.cmpb.2019.105303
Arabian T, Amjad-Iranagh S, Halladj R. Molecular dynamics simulation study of doxorubicin adsorption on functionalized carbon nanotubes with folic acid and tryptophan. Scientific Reports. 2021; 11(1). doi: 10.1038/s41598-021-03619-8
Siani P, Donadoni E, Ferraro L, et al. Molecular dynamics simulations of doxorubicin in sphingomyelin-based lipid membranes. Biochimica et Biophysica Acta (BBA)—Biomembranes. 2022; 1864(1): 183763. doi: 10.1016/j.bbamem.2021.183763
Ke Q, Gong X, Liao S, et al. Effects of thermostats/barostats on physical properties of liquids by molecular dynamics simulations. Journal of Molecular Liquids. 2022; 365: 120116. doi: 10.1016/j.molliq.2022.120116
Van Der Spoel D, Lindahl E, Hess B, et al. GROMACS: Fast, flexible, and free. Journal of Computational Chemistry. 2005; 26(16): 1701-1718. doi: 10.1002/jcc.20291
Kutzner C, Kniep C, Cherian A, et al. GROMACS in the Cloud: A Global Supercomputer to Speed Up Alchemical Drug Design. Journal of Chemical Information and Modeling. 2022; 62(7): 1691-1711. doi: 10.1021/acs.jcim.2c00044
Darden T, York D, Pedersen L. Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems. The Journal of Chemical Physics. 1993; 98(12): 10089-10092. doi: 10.1063/1.464397
Humphrey W, Dalke A, Schulten K. VMD: Visual molecular dynamics. Journal of Molecular Graphics. 1996; 14(1): 33-38.
Lu T, Chen F. Multiwfn: A multifunctional wavefunction analyzer. Journal of Computational Chemistry. 2011; 33(5): 580-592. doi: 10.1002/jcc.22885
Lefebvre C, Rubez G, Khartabil H, et al. Accurately extracting the signature of intermolecular interactions present in the NCI plot of the reduced density gradient versus electron density. Physical Chemistry Chemical Physics. 2017; 19(27): 17928-17936. doi: 10.1039/c7cp02110k
Zhu Y, Wang J, Vanga SK, et al. Visualizing structural changes of egg avidin to thermal and electric field stresses by molecular dynamics simulation. LWT. 2021; 151: 112139. doi: 10.1016/j.lwt.2021.112139
Sica MP, Kortsarz MV, Morillas AA, et al. Protocol to study the oligomeric organization of single-span transmembrane peptides using molecular dynamics simulations. STAR Protocols. 2022; 3(3): 101636. doi: 10.1016/j.xpro.2022.101636
Abdulkareem U, Kartha TR, Madhurima V. Radial distribution and hydrogen bonded network graphs of alcohol-aniline binary mixture. Journal of Molecular Modeling. 2023; 29(5). doi: 10.1007/s00894-023-05558-9
Zhao Q, Gao H, Su Y, et al. Experimental characterization and molecular dynamic simulation of ketoprofen-cyclodextrin complexes. Chemical Physics Letters. 2019; 736: 136802. doi: 10.1016/j.cplett.2019.136802
Zhu X, Huang Y. Theoretical study on paramagnetic amino carbon nanotube as fluorouracil drug delivery system. Journal of Drug Delivery Science and Technology. 2022; 75: 103670. doi: 10.1016/j.jddst.2022.103670
Hasanzade Z, Raissi H. Molecular mechanism for the encapsulation of the doxorubicin in the cucurbit[n]urils cavity and the effects of diameter, protonation on loading and releasing of the anticancer drug: Mixed quantum mechanical/ molecular dynamics simulations. Computer Methods and Programs in Biomedicine. 2020; 196: 105563. doi: 10.1016/j.cmpb.2020.105563
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