Abstract
In the present work, a new type of pH-responsive drug delivery system was successfully designed that is based on Fe3O4 magnetic nanoparticles functionalized with cucurbit[6]uril by thiol-ene click reaction. Various characterization experiments, such as SEM, TEM, FT-IR, XRD, XPS, and VSM, were performed to research the microstructure, morphology, composition, and physicochemical property of the prepared materials in detail. Then, the prepared cucurbit[6]uril-functionalized Fe3O4 magnetic nanoparticles were used to research the loading efficiency, loading capacity, and release percentage of doxorubicin. In the meantime, the influence of sample volume, loading time, pH, temperature, sample concentration, and carrier dosage on the loading efficiency was assessed and in vitro drug release behavior of doxorubicin in phosphate buffer solution with different pH values (3.0, 5.5, and 7.4) was examined. The results demonstrated that the developed drug delivery system based on cucurbit[6]uril-functionalized Fe3O4 magnetic nanoparticles showed high loading efficiency and pH-responsive controlled release behavior.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Angelos S, Yang YW, Patel K, Stoddart JF, Zink JI (2008) pH-responsive supramolecular nanovalves based on cucurbit[6]uril pseudorotaxanes. Angew Chem Int Ed 47(12):2222–2226. https://doi.org/10.1002/anie.200705211
Anirudhan TS, Sandeep S (2012) Synthesis, characterization, cellular uptake and cytotoxicity of a multi-functional magnetic nanocomposite for the targeted delivery and controlled release of doxorubicin to cancer cells. J Mater Chem 22(25):12888–12899. https://doi.org/10.1039/c2jm31794j
Bhattacharjee A, Gumma S, Purkait MK (2018) Fe3O4 promoted metal organic framework MIL-100(Fe) for the controlled release of doxorubicin hydrochloride. Microporous Mesoporous Mater 259:203–210. https://doi.org/10.1016/j.micromeso.2017.10.020
Cai W, Wang JQ, Chu CC, Chen W, Wu CS, Liu G (2019a) Metal-organic framework-based stimuli-responsive systems for drug delivery. Adv Sci 6(1):1801526–1801546. https://doi.org/10.1016/j.msec.2018.12.145
Cai WL, Guo MY, Weng XL, Zhang W, Chen ZL (2019b) Adsorption of doxorubicin hydrochloride on glutaric anhydride functionalized Fe3O4@SiO2 magnetic nanoparticles. Mater Sci Eng C 98:65–73. https://doi.org/10.1016/j.msec.2018.12.145
Cai WL, Guo MY, Weng XL, Zhang W, Owens G, Chen ZL (2020) Modified green synthesis of Fe3O4@SiO2 nanoparticles for pH responsive drug release. Mater Sci Eng C 112:110900–110908. https://doi.org/10.1016/j.msec.2020.110900
Gu ZK, Dong YR, Xu SX, Wang LS, Liu Z (2020) Molecularly imprinted polymer-based smart prodrug delivery system for specific targeting, prolonged retention and tumor microenvironment-triggered release. Angew Chem Int Ed. https://doi.org/10.1002/anie.202012956
Huang XL, Tan YB, Zhou QF, Wang YX (2008) Fabrication of cucurbit[6]uril mediated alginate physical hydrogel beads and their application as a drug carriers. e-Polymers. https://doi.org/10.1515/epoly.2008.8.1.1098
Huang XL, Zhang NQ, Ban LZ, Su HQ (2015) Synthesis of star poly(N-isopropylacrylamide) with a core of cucurbit[6]uril via ATRP and controlled thermoresponsivity. Macromol Rapid Commun 36(3):311–319. https://doi.org/10.1002/marc.201400506
Javadian S, Najafi K, Sadrpoor SM, Ektefa F, Dalir N, Nikkhah M (2021) Graphene quantum dots based magnetic nanoparticles as a promising delivery system for controlled doxorubicin release. J Mol Liq 331:115746–115754. https://doi.org/10.1016/j.molliq.2021.115746
Javanbakht S, Nazari N, Rakhshaei R, Namazi H (2018) Cu-crosslinked carboxymethylcellulose/naproxen/graphene quantum dot nanocomposite hydrogel beads for naproxen oral delivery. Carbohydr Polym 195:453–459. https://doi.org/10.1016/j.carbpol.2018.04.103
Jeon Y-M, Kim J, Whang D, Kim K (1996) Molecular container assembly capable of controlling binding and release of its guest molecules: reversible encapsulation of organic molecules in sodium ion complexed cucurbituril. J Am Chem Soc 118:9790–9791. https://doi.org/10.1021/ja962071x
Jiang DD, Li XQ, Jia Q (2018) Multilayer cucurbit[6]uril-based magnetic nanoparticles prepared by host-guest interaction: remarkable adsorbent for low density lipoprotein removal from plasma. Chem Eur J 24(9):2242–2248. https://doi.org/10.1002/chem.201705280
Jin RR, Wang JX, Gao MX, Zhang XM (2021) Pollen-like silica nanoparticles as a nanocarrier for tumor targeted and pH-responsive drug delivery. Talanta 231:122402–122409. https://doi.org/10.1016/j.talanta.2021.122402
Kamaly N, Yameen B, Wu J, Farokhzad OC (2016) Degradable controlled-release polymers and polymeric nanoparticles: mechanisms of controlling drug release. Chem Rev 116(4):2602–2663. https://doi.org/10.1021/acs.chemrev.5b00346
Kim S, Yun G, Khan S, Kim J, Murray J, Lee YM, Kim WJ, Lee G, Kim S, Shetty D et al (2017) Cucurbit[6]uril-based polymer nanocapsules as a non-covalent and modular bioimaging platform for multimodal in vivo imaging. Mater Horiz 4(3):450–455. https://doi.org/10.1039/c7mh00038c
Li FZ, Mei L, Hu KQ, Yu JP, An SW, Liu K, Chai ZF, Liu N, Shi WQ (2018) Releasing metal-coordination capacity of cucurbit[6]uril macrocycle in pseudorotaxane ligands for the construction of interwoven uranyl-rotaxane coordination polymers. Inorg Chem 57(21):13513–13523. https://doi.org/10.1021/acs.inorgchem.8b02126
Li J, Liu MM, Qiu YJ, Gan YJ, Jiang HK, Liu BY, Wei H, Ma N (2021a) Urchin-like hydroxyapatite/graphene hollow microspheres as pH-responsive bone drug carriers. Langmuir 37(14):4137–4146. https://doi.org/10.1021/acs.langmuir.0c03640
Li JX, Si CY, Sun HC, Zhu JY, Pan TZ, Liu SD, Dong ZY, Xu JY, Luo Q, Liu JQ (2015) Reversible pH-controlled switching of an artificial antioxidant selenoenzyme based on pseudorotaxane formation and dissociation. Chem Commun 51:9987–9990. https://doi.org/10.1039/C5CC02038G
Li S, Zhang RZ, Wang DX, Feng L, Cui K (2021b) Synthesis of hollow maghemite (<gamma>-Fe2O3) particles for magnetic field and pH-responsive drug delivery and lung cancer treatment. Ceram Int 47(6):7457–7464. https://doi.org/10.1016/j.ceramint.2020.11.086
Li YL, Yang YF, Pei XQ, Li Y, Yuan YH, Huang XL (2021c) Synthesis of cucurbit[6]uril pendent upper critical solution temperature type copolymers: self-assembly and multi-stimuli-responsive behavior. Polym Int. https://doi.org/10.1002/pi.6211
Liu L, Jiang HL, Dong J, Zhang WX, Dang GY, Yang MF, Li YY, Chen HY, Ji HW, Dong LF (2020) PEGylated MoS2 quantum dots for traceable and pH-responsive chemotherapeutic drug delivery. Colloids Surf B 185:110590–110599. https://doi.org/10.1016/j.colsurfb.2019.110590
Lv FY, Liu DP, Cong HL, Shen YQ, Yu B (2019) Synthesis, self-assembly and drug release behaviors of a bottlebrush polymer-HCPT prodrug for tumor chemotherapy. Colloids Surf B 181:278–284. https://doi.org/10.1016/j.colsurfb.2019.05.045
Mahesh AG, Narsireddy A, Madhusudana Rao N, Manorama SV (2018) A simple approach to design chitosan functionalized Fe3O4 nanoparticles for pH responsive delivery of doxorubicin for cancer therapy. J Magn Magn Mater 448:199–207. https://doi.org/10.1016/j.jmmm.2017.09.018
Naqvi STR, Rasheed T, Hussain D, Majeed S, Fatima B, Haq MNu, Zarin A, Nawaz R (2020) Development of molecularly imprinted magnetic iron oxide nanoparticles for doxorubicin drug delivery. Monatsh Chem 151(7):1049–1057. https://doi.org/10.1007/s00706-020-02644-z
Nejad MA, Umstatter P, Urbassek HM (2020) Boron nitride nanotubes as containers for targeted drug delivery of doxorubicin. J Mol Model 26(3):54–63. https://doi.org/10.1007/s00894-020-4305-z
Qiu XL, Zhou Y, Jin XY, Qi AD, Yang YW (2015) One-pot solvothermal synthesis of biocompatible magnetic nanoparticles mediated by cucurbit[n]urils. J Mater Chem C 3(15):3517–3521. https://doi.org/10.1039/c5tc00369e
Ruzycka-Ayoush M, Kowalik P, Kowalczyk A, Bujak P, Nowicka AM, Wojewodzka M, Kruszewski M, Grudzinski IP (2021) Quantum dots as targeted doxorubicin drug delivery nanosystems in human lung cancer cells. Cancer Nano. https://doi.org/10.1186/s12645-021-00077-9
Samadi S, Moradkhani M, Beheshti H, Irani M, Aliabadi M (2018) Fabrication of chitosan/poly(lactic acid)/graphene oxide/TiO2 composite nanofibrous scaffolds for sustained delivery of doxorubicin and treatment of lung cancer. Int J Biol Macromol 110:416–424. https://doi.org/10.1016/j.ijbiomac.2017.08.048
Santos SBF, Araújo PMAGd, Santos IAd, Costa ACFdM, Lima ÁS, Conrado LdS (2021) Site-directed drug release performance in chemically-modified FeFe2O4 and CoFe2O4 magnetic nanoparticles for controlled drug delivery systems. Ceram Int 47(14):19622–19631. https://doi.org/10.1016/j.ceramint.2021.03.300
Shao L, Wang XF, Ren YM, Wang SF, Zhong JR, Chu MF, Tang H, Luo LZ, Xie DH (2016) Facile fabrication of magnetic cucurbit[6]uril/graphene oxide composite and application for uranium removal. Chem Eng J 286:311–319. https://doi.org/10.1016/j.cej.2015.10.062
Shi YQ, Wang YX, Zhu JH, Liu W, Khan MZH, Liu XH (2020) Molecularly imprinting polymers (MIP) based on nitrogen doped carbon dots and mIL-101(Fe) for doxorubicin hydrochloride delivery. Nanomaterials 10(9):1655–1670. https://doi.org/10.3390/nano10091655
Siavashy S, Soltani M, Ghorbani-Bidkorbeh F, Fallah N, Farnam G, Mortazavi SA, Shirazi FH, Tehrani MHH, Hamedi MH (2021) Microfluidic platform for synthesis and optimization of chitosan-coated magnetic nanoparticles in cisplatin delivery. Carbohydr Polym 265:118027–118043. https://doi.org/10.1016/j.carbpol.2021.118027
Soheyla K, Hassan N (2021) Fe3O4@PEG-coated dendrimer modified graphene oxide nanocomposite as a pH-sensitive drug carrier for targeted delivery of doxorubicin. J Alloys Compd 879:160426–160438. https://doi.org/10.1016/j.jallcom.2021.160426
Song N, Kakuta T, Yamagishi T-a, Yang Y-W, Ogoshi T (2018) Molecular-scale porous materials based on pillar[n]arenes. Chem 4(9):2029–2053. https://doi.org/10.1016/j.chempr.2018.05.015
Trivedi MU, Patlolla CK, Misra NM, Pandey MK (2019) Cucurbit[6]uril glued magnetic clay hybrid as a catalyst for nitrophenol reduction. Catal Lett 149(9):2355–2367. https://doi.org/10.1007/s10562-019-02853-0
Verma G, Barick KC, Shetake NG, Pandey BN, Hassan PA (2016) Citrate-functionalized hydroxyapatite nanoparticles for pH-responsive drug delivery. RSC Adv 6(81):77968–77976. https://doi.org/10.1039/c6ra10659e
Wang F, Geng JH, Qi XW, Zhang P, Zhang H, He XL, Li ZJ, Yu RT, Li JQ, Li BW, Wang GS (2021) Facile solvothermal synthesis of monodisperse superparamagnetic mesoporous Fe3O4 nanospheres for pH-responsive controlled drug delivery. Colloids Surf A 622:126643–126651. https://doi.org/10.1016/j.colsurfa.2021.126643
Wang X, Li C, Fan N, Li J, He Z, Sun J (2017) Multimodal nanoporous silica nanoparticles functionalized with aminopropyl groups for improving loading and controlled release of doxorubicin hydrochloride. Mater Sci Eng C 78:370–375. https://doi.org/10.1016/j.msec.2017.04.060
Yang H, Yuan B, Zhang X, Scherman OA (2014) Supramolecular chemistry at interfaces: host-guest interactions for fabricating multifunctional biointerfaces. Acc Chem Res 47(7):2106–2115. https://doi.org/10.1021/ar500105t
Yu B, Yang B, Li GL, Cong HL (2018a) Preparation of monodisperse cross-linked poly(glycidyl methacrylate)@Fe3O4@diazoresin magnetic microspheres with dye removal property. J Mater Sci 53(9):6471–6481. https://doi.org/10.1007/s10853-018-2018-9
Yu GC, Zhao XL, Zhou J, Mao ZW, Huang XL, Wang ZT, Hua B, Liu YL, Zhang FW, He ZM, Jacobson O, Gao CY, Wang WL, Yu CY, Zhu XY, Huang FH, Chen XY (2018b) Supramolecular polymer-based nanomedicine: high therapeutic performance and negligible long-term immunotoxicity. J Am Chem Soc 140(25):8005–8019. https://doi.org/10.1021/jacs.8b04400
Zeng SJ, Quan X, Zhu HL, Sun DL, Miao ZH, Zhang LH, Zhou J (2021) Computer simulations on a pH-responsive anticancer drug delivery system using zwitterion-grafted polyamidoamine dendrimer unimolecular micelles. Langmuir 37(3):1225–1234. https://doi.org/10.1021/acs.langmuir.0c03217
Zhang K, Sun WQ, Lin RL, Xiao X, Bian B, Tao Z, Liu JX (2019a) Controlled encapsulation and release of an organic guest in the cavity of α, α′, δ, δ′-tetramethylcucurbit[6]uril. Eur J Org Chem 7:1503–1507. https://doi.org/10.1002/ejoc.201801652
Zhang XD, Zhao Y, Chen K, Guo JH, Wang P, Wu H, Sun WY (2019b) Cucurbit[6]uril-based supramolecular assemblies incorporating metal complexes with multiaromatic ligands as structure-directing agent for detection of aromatic amines and nitroaromatic compounds. Sens Actuators B 282:844–853. https://doi.org/10.1016/j.snb.2018.11.128
Zhang N, Wang DQ, Yang TT, Jing X, Meng LJ (2021) Construction of hyperbranched and pH-responsive polymeric nanocarriers by yne-phenol click-reaction for tumor synergistic chemotherapy. Colloids Surf B 204:111790–111799. https://doi.org/10.1016/j.colsurfb.2021.111790
Zirak M, Abdollahiyan A, Eftekhari-Sis B, Saraei M (2017) Carboxymethyl cellulose coated Fe3O4@SiO2 core–shell magnetic nanoparticles for methylene blue removal: equilibrium, kinetic, and thermodynamic studies. Cellulose 25(1):503–515. https://doi.org/10.1007/s10570-017-1590-5
Acknowledgements
We gratefully acknowledge funding support from the Changzhou Science and Technology Project (CJ20200033). Instruments provided by the Analysis and Testing Center of Jiangsu University of Technology are also gratefully appreciated.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no competing financial interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Liu, D., Huang, L., Li, T. et al. Cucurbit[6]uril-functionalized Fe3O4 magnetic nanoparticles for pH-responsive drug delivery. Chem. Pap. 76, 3853–3862 (2022). https://doi.org/10.1007/s11696-022-02147-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11696-022-02147-7