Abstract
In this study, hyaluronic acid-functionalized disulfide hollow mesoporous silica nanoparticles (HMSN-NH2-HA) were synthesized as an anticancer drug delivery system. In this regard, hyaluronic acid, a natural ligand for cluster of differentiation-44 (CD44) receptors overexpressed on the surface of tumor cells, was covalently grafted onto the HMSNs. The nanoparticles were characterized using various techniques, such as transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR). Doxorubicin hydrochloride (DOX) was loaded into HMSN-NH2-HA as a model medication. The in vitro drug release was evaluated in different medium conditions and was analyzed by high-performance liquid chromatography. Cellular viability and the localization of nanoparticles were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and confocal microscopy. The in vivo release of DOX in BALB/c mice was investigated by ex vivo images obtained by fluorescence microscopy. The TEM images of HMSNs revealed hollow spheres with an average size of approximately 150 nm. After grafting the HMSNs with hyaluronic acid, the hydrodynamic size of nanoparticles increased to 197 nm, and the zeta potential changed from − 40 to − 18 mV. The half inhibitory concentration (IC50) of HMSN-NH2-HA@DOX and HMSN@DOX for MDA-MB-231 cells after 48 h was 0.32 and 0.21 µg/ml, respectively. Ex vivo biodistribution analysis showed that the tumor-to-nontumor ratio was higher in the HMSN-NH2-HA@DOX group compared to the DOX group. This nanoparticle could provide new opportunities for DOX tumor delivery owing to its biodegradability, controlled release, and targeting behavior.
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References
Abbasi M, Hafez S, Hadi M, Jamali K, Moeini Z, Jangjou A, Izadpanah P, Mohammad A (2021) Microporous and mesoporous materials mesoporous silica nanoparticle : heralding a brighter future in cancer nanomedicine, microporous mesoporous mater. 319 110967. https://doi.org/10.1016/j.micromeso.2021.110967.
Almalik A, Benabdelkamel H, Masood A, Alanazi IO, Majrashi MA, Alfadda AA, Alghamdi WM, Alrabiah H (2017) Hyaluronic acid coated chitosan nanoparticles reduced the immunogenicity of the formed protein corona. Sci Rep 7(1):1–9. https://doi.org/10.1038/s41598-017-10836-7
AAT Bioquest, Inc, Quest GraphTM IC50 Calc. https://www.aatbio.com/tools/ic50-calculator (accessed July 5, 2021).
Chen F, Hong H, Shi S, Goel S, Valdovinos HF, Hernandez R, Theuer CP, Barnhart TE, Cai W (2014) Engineering of hollow mesoporous silica nanoparticles for remarkably enhanced tumor active targeting. Sci Rep 105. https://doi.org/10.1038/srep05080
Decuzzi P, Godin B, Tanaka T, Lee SY, Chiappini C, Liu X, Ferrari M (2010) Size and shape effects in the biodistribution of intravascularly injected particles. J Control Release 141:320–327. https://doi.org/10.1016/j.jconrel.2009.10.014
Fanciullino R, Ciccolini J, Milano G (2013) Challenges, expectations and limits for nanoparticles-based therapeutics in cancer : a focus on nano-albumin-bound drugs. Crit Rev Oncol / Hematol 88:504–513. https://doi.org/10.1016/j.critrevonc.2013.06.010
Fang J, Islam W, Maeda H (2020) Exploiting the dynamics of the EPR effect and strategies to improve the therapeutic effects of nanomedicines by using EPR effect enhancers. Adv Drug Deliv Rev 157:142–160. https://doi.org/10.1016/j.addr.2020.06.005
Ghosh S, Dutta S, Sarkar A, Kundu M, Sil PC (2021) Targeted delivery of curcumin in breast cancer cells via hyaluronic acid modified mesoporous silica nanoparticle to enhance anticancer efficiency. Colloids Surfaces B Biointerfaces 197:111404. https://doi.org/10.1016/j.colsurfb.2020.111404
Goodarzi N, Ghahremani MH, Amini M, Atyabi F, Ostad SN, ShabaniRavari N, Nateghian N, Dinarvand R (2014) CD44-targeted docetaxel conjugate for cancer cells and cancer stem-like cells: a novel hyaluronic acid-based drug delivery system. Chem Biol Drug Des 83:741–752. https://doi.org/10.1111/cbdd.12288
Goodarzi N, Ghahremani MH, Dinarvand R (2011) Targeting CD44 by hyaluronic acid-based nano drug delivery systems may eradicate cancer stem cells in human breast cancer. Iran J Med Hypotheses Ideas 5 1–5. https://ijmhi.tums.ac.ir/index.php/ijmhi/article/view/115
HadipourMoghaddam SP, Yazdimamaghani M, Ghandehari H (2018) Glutathione-sensitive hollow mesoporous silica nanoparticles for controlled drug delivery. J Control Release 282:62–75. https://doi.org/10.1016/j.jconrel.2018.04.032
Hai L, Jia X, He D, Zhang A, Wang T, Cheng H, He X, Wang K (2018) DNA-functionalized hollow mesoporous silica nanoparticles with dual cargo loading for near-infrared-responsive synergistic chemo-photothermal treatment of cancer cells. ACS Appl Nano Mater 1:3486–3497. https://doi.org/10.1021/acsanm.8b00657
Hao X, Hu X, Zhang C, Chen S, Li Z, Yang X, Liu H, Jia G, Liu D, Ge K, Liang XJ, Zhang J (2015) Hybrid mesoporous silica-based drug carrier nanostructures with improved degradability by hydroxyapatite. ACS Nano 9:9614–9625. https://doi.org/10.1021/nn507485j
Hillaireau H, Couvreur P (2009) Nanocarriers’ entry into the cell: relevance to drug delivery. Cell Mol Life Sci 66:2873–2896. https://doi.org/10.1007/s00018-009-0053-z
Jahns M, Warwas DP, Krey MR, Nolte K, König S, Fröba M, Behrens P (2019) Nanoporous hybrid core–shell nanoparticles for sequential release. J Mater Chem B 8(4):776–786. https://doi.org/10.1039/C9TB01846H
Kabiri F, Mirfakhraee S, Ardakani YH, Dinarvand R (2021) Hollow mesoporous silica nanoparticles for co-delivery of hydrophobic and hydrophilic molecules: mechanism of drug loading and release. J Nanopart Res 23:226. https://doi.org/10.1007/s11051-021-05332-z
Khoee S, Bafkary R, Fayyazi F (2017) DOX delivery based on chitosan-capped graphene oxide- mesoporous silica nanohybride as pH-responsive nanocarriers. J Sol-Gel Sci Technol 493–504. https://doi.org/10.1007/s10971-016-4213-y
Khosravian P, Ardestani MS, Khoobi M, Ostad SN, Dorkoosh FA, Javar HA, Amanlou M (2016) Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel. Onco Targets Ther 9:7315. https://doi.org/10.2147/OTT.S113815
Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B (2017) The different mechanisms of cancer drug resistance : a brief review, Tabriz Univ. Med Sci 7:339–348. https://doi.org/10.15171/apb.2017.041
Moorthi C, Manavalan R, Kathiresan K (2011) Nanotherapeutics to overcome conventional cancer chemotherapy limitations. J Pharm Pharm Sci 14:67–77. https://doi.org/10.18433/j30c7d
Mosleh-shirazi S, Abbasi M, Shafiee M, Reza S, Mohammad A (2021) Renal clearable nanoparticles : an expanding horizon for improving biomedical imaging and cancer therapy. Mater Today Commun 26:102064. https://doi.org/10.1016/j.mtcomm.2021.102064
Narayan R, Nayak UY (2018) Mesoporous silica nanoparticles : a comprehensive review on synthesis and recent advances, 1–49. https://doi.org/10.3390/pharmaceutics10030118
Narvekar M, Xue HY, Eoh JY, Wong HL (2014) Nanocarrier for poorly water-soluble anticancer drugs — barriers of translation and solutions, 15 822–833 https://doi.org/10.1208/s12249-014-0107-x
Ramadan MH, Prata JE, Kara O, Washburn NR (2014) Reducing protein adsorption with polymer-grafted hyaluronic acid coatings. Langmuir 30(25):7485–95. https://doi.org/10.1021/la500918p
Saadat E, Amini M, Khoshayand MR, Dinarvand R, Dorkoosh FA (2014) Synthesis and optimization of a novel polymeric micelle based on hyaluronic acid and phospholipids for delivery of paclitaxel, in vitro and in-vivo evaluation. Int J Pharm 475:163–173. https://doi.org/10.1016/j.ijpharm.2014.08.030
ShabaniRavari N, Goodarzi N, Alvandifar F, Amini M, Souri E, Khoshayand MR, HadavandMirzaie Z, Atyabi F, Dinarvand R (2016) Fabrication and biological evaluation of chitosan coated hyaluronic acid-docetaxel conjugate nanoparticles in CD44+ cancer cells. DARU J Pharm Sci 24:1–12. https://doi.org/10.1186/s40199-016-0160-y
Shao XR, Wei XQ, Song X, Hao LY, Cai XX, Zhang ZR, Peng Q, Lin YF (2015) Independent effect of polymeric nanoparticle zeta potential/surface charge, on their cytotoxicity and affinity to cells. Cell Prolif 48:465–474. https://doi.org/10.1111/cpr.12192
Shapero K, Fenaroli F, Lynch I, Cottell DC, Salvati A, Dawson KA (2011) Time and space resolved uptake study of silica nanoparticles by human cells. Mol Biosyst 7:371–378. https://doi.org/10.1039/c0mb00109k
Sun J, Hong C, Pan C (2010) Fabrication of PDEAEMA-coated mesoporous silica nanoparticles and pH-responsive controlled release. J Phys Chem C 114:12481–12486. https://doi.org/10.1021/jp103982a
Toniolo G, Efthimiadou EK, Kordas G, Chatgilialoglu C (2018) Development of multi-layered and multi-sensitive polymeric nanocontainers for cancer therapy: in vitro evaluation. Sci Rep 8:1–9. https://doi.org/10.1038/s41598-018-32890-5
Wang Y, Zhao Q, Han N, Bai L, Li J, Liu J, Che E, Hu L, Zhang Q, Jiang T, Wang S (2015) Mesoporous silica nanoparticles in drug delivery and biomedical applications, Nanomedicine Nanotechnology. Biol Med 11:313–327. https://doi.org/10.1016/j.nano.2014.09.014
Watermann A, Brieger J (2017) Mesoporous silica nanoparticles as drug delivery vehicles in cancer. Nanomaterials 7. https://doi.org/10.3390/nano7070189.
Wen J, Yang K, Liu F, Li H, Xu Y, Sun S (2017) Diverse gatekeepers for mesoporous silica nanoparticle based drug delivery systems. Chem Soc Rev 46:6024–6045. https://doi.org/10.1039/c7cs00219j
Xu C, Lei C, Yu C (2019) Mesoporous silica nanoparticles for protein protection and delivery. Front Chem 7:290. https://doi.org/10.3389/fchem.2019.00290
Xu H, Niu M, Yuan X, Wu K, Liu A (2020) CD44 as a tumor biomarker and therapeutic target. Exp Hematol Oncol 9:1–14. https://doi.org/10.1186/s40164-020-00192-0
Z P, Guo Y, Wang L, Lv P (2015) Transferrin-conjugated doxorubicin-loaded lipid-coated nanoparticles for the targeting and therapy of lung cancer. Oncol Lett 9(3):1065–1072. https://doi.org/10.3892/ol.2014.2840
Zhai W, He C, Wu L, Zhou Y, Chen H, Chang J (2012) Degradation of hollow mesoporous silica nanoparticles in human umbilical vein endothelial cells. J Biomed Mater Res Part B Appl Biomater 100(5):1397–1403. https://doi.org/10.1002/jbm.b.32711
Zhang J, Sun Y, Tian B, Li K, Wang L, Liang Y, Han J (2016) Multifunctional mesoporous silica nanoparticles modified with tumor-shedable hyaluronic acid as carriers for doxorubicin. Colloids Surf B Biointerfaces 144:293–302. https://doi.org/10.1016/j.colsurfb.2016.04.015
Zhou J, Romero G, Rojas E, Ma L, Moya S, Gao C (2010) Journal of Colloid and Interface Science Layer by layer chitosan / alginate coatings on poly ( lactide-co-glycolide ) nanoparticles for antifouling protection and Folic acid binding to achieve selective cell targeting. J Colloid Interface Sci 345:241–247. https://doi.org/10.1016/j.jcis.2010.02.004
Acknowledgements
This research has received a specific grant from the Tehran University of Medical Sciences (No. 285122). The authors would like to thank the Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences for their support.
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Mirfakhraee, S., Bafkary, R., Ardakani, Y.H. et al. Synthesis of hyaluronic acid-grafted hollow mesoporous silica nanoparticles as nano-carriers for anticancer drug delivery. J Nanopart Res 24, 100 (2022). https://doi.org/10.1007/s11051-022-05478-4
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DOI: https://doi.org/10.1007/s11051-022-05478-4