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Mesoporous silica nanoparticles with cyclic peptide gatekeeper for stimulus-responsive drug release by conformational transformation

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Abstract

For the preparation of drug delivery vehicles, peptides have been widely adopted due to their valuable bioresponsiveness. In addition, the conformational change of peptides in response to a particular bioenvironment could be adopted as a talented motif for the on-demand release of loaded cargos in mesoporous silica nanoparticles. Here, a cyclic peptide gatekeeper with an intramolecular disulfide bond for on–off triggered gatekeeping and NEWQG sequence for selective binding is prepared. The cyclic peptide gatekeeper conjugated onto the surface of mesoporous silica nanoparticles completely blocks the undesirable leakage of loaded cargos in the pore. Upon treatment of biological reducing agent, the entrapped drugs in the pore of the nanoparticles are released selectively over time by specific reduction of the cystine unit and thereby conformational transformation of the peptide gatekeeper.

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Abbreviations

APTES:

3-Aminopropyltriethoxysilane

CTAB:

Hexadecyltrimethylammonium bromide

DIPEA:

N,Nʹ-diisopropylethylamine

DLS:

Dynamic light scattering

DMF:

N,Nʹ-dimethylformamide

DOX:

Doxorubicin

FE-SEM:

Field-emission scanning electron microscopy

FT-IR:

Fourier transform infrared spectroscopy

GSH:

Glutathione

HBTU:

O-(benzotriazol-1-yl)-N,N,Nʹ,Nʹ-tetramethyluronium hexafluorophosphate

HMDI:

Hexamethylene diisocyanate

HOBt:

1-Hydroxybenzotriazole (HOBt)

MeO-PEG-OH:

Poly(ethylene glycol) monomethyl ether

MSNs:

Mesoporous silica nanoparticles

TEM:

Transmission electron microscopy

TEOS:

Tetraethyl orthosilicate

TFA:

Trifluoroacetic acid

TIS:

Triisopropylsilane

References

  • Alberti S, Soler-Illia GJAA, Azzaroni O (2015) Gated supramolecular chemistry in hybrid mesoporous silica nanoarchitectures: controlled delivery and molecular transport in response to chemical, physical and biological stimuli. Chem Commun 51(28):6050–6075

    Article  CAS  Google Scholar 

  • Aznar E, Oroval M, Pascual L, Murguía JRn, Martínez-Máñez Rn, Sancenón Fl (2016) Gated materials for on-command release of guest molecules. Chem Rev 116(2):561–718

    Article  CAS  Google Scholar 

  • Balendiran GK, Dabur R, Fraser D (2004) The role of glutathione in cancer. Cell Biochem Funct 22(6):343–352

    Article  CAS  Google Scholar 

  • Coll C, Mondragón L, Martínez-Máñez R, Sancenón F, Marcos MD, Soto J, Amorós P, Pérez-Payá E (2011) Enzyme-mediated controlled release systems by anchoring peptide sequences on mesoporous silica supports. Angew Chem Int Ed 50(9):2138–2140

    Article  CAS  Google Scholar 

  • Coll C, Bernardos A, Martínez-Máñez R, Sancenón F (2013) Gated silica mesoporous supports for controlled release and signaling applications. Acc Chem Res 46(2):339–349

    Article  CAS  Google Scholar 

  • Colombo G, Curnis F, De Mori GMS, Gasparri A, Longoni C, Sacchi A, Longhi R, Corti A (2002) Structure-activity relationships of linear and cyclic peptides containing the ngr tumor-homing motif. J Biol Chem 277(49):47891–47897

    Article  CAS  Google Scholar 

  • Copolovici DM, Langel K, Eriste E, Langel Ü (2014) Cell-penetrating peptides: design, synthesis, and applications. ACS Nano 8(3):1972–1994

    Article  CAS  Google Scholar 

  • Estrela JM, Ortega A, Obrador E (2006) Glutathione in cancer biology and therapy. Crit Rev Clin Lab Sci 43(2):143–181

    Article  CAS  Google Scholar 

  • Fields GB, Noble RL (1990) Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int J Pept Protein Res 35(3):161–214

    Article  CAS  Google Scholar 

  • Kim H, Kim S, Park C, Lee H, Park HJ, Kim C (2010) Glutathione-induced intracellular release of guests from mesoporous silica nanocontainers with cyclodextrin gatekeepers Adv. Mater 22(38):4280–4283

    CAS  Google Scholar 

  • Kresge CT, Leonowicz ME, Roth WJ, Vartuli JC, Beck JS (1992) Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature 359(6397):710–712

    Article  CAS  Google Scholar 

  • Lee J, Han S, Lee J, Choi M, Kim C (2017a) Stimuli-responsive α-helical peptide gatekeepers for mesoporous silica nanocarriers. New J Chem 41(15):6969–6972

    Article  CAS  Google Scholar 

  • Lee J, Oh E-T, Han Y, Kim HG, Park HJ, Kim C (2017b) Mesoporous silica nanocarriers with cyclic peptide gatekeeper: specific targeting of aminopeptidase n and triggered drug release by stimuli-responsive conformational transformation. Chem Eur J 23(67):16966–16971

    Article  CAS  Google Scholar 

  • Lee J, Oh E-T, Song J, Kim HG, Park HJ, Kim C (2017c) Stimulus-induced conformational transformation of cyclic peptide for selective cell targeting on-off gatekeeper of mesoporous nanocarrier. Chem Asian J 12(21):2813–2818

    Article  CAS  Google Scholar 

  • Lee J, Oh E-T, Choi MH, Kim HG, Park HJ, Kim C (2018) Dual-functional cyclic peptide switch on mesoporous nanocontainers for selective cd44 targeting and on-off gatekeeping triggered by conformational transformation. New J Chem 42(15):12938–12944

    Article  CAS  Google Scholar 

  • Lee J, Oh E-T, Lee J, Kang T, Kim HG, Kang H, Park HJ, Kim C (2019) Cyclic irgd peptide as a dual-functional on-off gatekeeper of mesoporous nanocontainers for targeting nrp-1 and selective drug release triggered by conformational conversion. New J Chem 43(3):1517–1522

    Article  CAS  Google Scholar 

  • Lee J, Oh E-T, Yoon H, Kim CW, Han Y, Song J, Jang H, Park HJ, Kim C (2017d) Mesoporous nanocarriers with stimulus-responsive cyclodextrin gatekeeper for targeting tumor hypoxia. Nanoscale 9(20):6901–6909

    Article  CAS  Google Scholar 

  • Lee J, Kim H, Kim S, Lee H, Kim J, Kim N, Park HJ, Choi EK, Lee JS, Kim C (2012) A multifunctional mesoporous nanocontainer with an iron oxide core and a cyclodextrin gatekeeper for an efficient theranostic platform. J Mater Chem 22(28):14061–14067

    Article  CAS  Google Scholar 

  • Lee J, Kim H, Kim C (2016a) Generation dependency of stimuli-responsive dendron-gated mesoporous silica nanocontainers. Macromol Res 24(5):478–481

    Article  CAS  Google Scholar 

  • Lee J, Oh E-T, Yoon H, Kim H, Park HJ, Kim C (2016b) A mesoporous nanocontainer gated by stimuli-responsive peptide for selective triggering of intracellular drug release. Nanoscale 8(15):8070–8077

    Article  CAS  Google Scholar 

  • Lee J, Kim H, Han S, Hong E, Lee K-H, Kim C (2014) Stimuli-responsive conformational conversion of peptide gatekeepers for controlled release of guests from mesoporous silica nanocontainers. J Am Chem Soc 136(37):12880–12883

    Article  CAS  Google Scholar 

  • Li L, Schmitt M, Matzke-Ogi A, Wadhwani P, Orian-Rousseau V, Levkin PA (2017) Cd44v6-peptide functionalized nanoparticles selectively bind to metastatic cancer cells. Adv Sci 4(1):1600202

    Article  Google Scholar 

  • Liu H, Wang H, Shenvi S, Hagen TM, Liu R-M (2004) Glutathione metabolism during aging and in alzheimer disease. Ann. N.Y. Acad Sci 1019:346–349

    Article  CAS  Google Scholar 

  • Majhen D, Gabrilovac J, Eloit M, Richardson J, Ambriović-Ristov A (2006) Disulfide bond formation in ngr fiber-modified adenovirus is essential for retargeting to aminopeptidase n. Biochem Biophys Res Commun 348(1):278–287

    Article  CAS  Google Scholar 

  • Matzke A, Herrlich P, Ponta H, Orian-Rousseau V (2005) A five-amino-acid peptide blocks met- and ron-dependent cell migration. Cancer Res 65(14):6105–6110

    Article  CAS  Google Scholar 

  • Matzke-Ogi A, Jannasch K, Shatirishvili M, Fuchs B, Chiblak S, Morton J, Tawk B, Lindner T, Sansom O, Alves F, Warth A, Schwager C, Mier W, Kleeff J, Ponta H, Abdollahi A, Orian-Rousseau V (2016) Inhibition of tumor growth and metastasis in pancreatic cancer models by interference with cd44v6 signaling. Gastroenterology 150(2):513–525

    Article  Google Scholar 

  • Mura S, Nicolas J, Couvreur P (2013) Stimuli-responsive nanocarriers for drug delivery. Nat Mater 12:991–1003

    Article  CAS  Google Scholar 

  • Paris JL, Cabañas MV, Manzano M, Vallet-Regí M (2015) Polymer-grafted mesoporous silica nanoparticles as ultrasound-responsive drug carriers. ACS Nano 9(11):11023–11033

    Article  CAS  Google Scholar 

  • Park C, Kim H, Kim S, Kim C (2009) Enzyme responsive nanocontainers with cyclodextrin gatekeepers and synergistic effects in release of guests. J Am Chem Soc 131(46):16614–16615

    Article  CAS  Google Scholar 

  • Slowing II, Vivero-Escoto JL, Wu C-W, Lin VSY (2008) Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv Drug Del Rev 60(11):1278–1288

    Article  CAS  Google Scholar 

  • Tang F, Li L, Chen D (2012) Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater 24(12):1504–1534

    Article  CAS  Google Scholar 

  • Thornton PD, Heise A (2010) Highly specific dual enzyme-mediated payload release from peptide-coated silica particles. J Am Chem Soc 132:2024–2028

    Article  CAS  Google Scholar 

  • Torre Cdl, Agostini A, Mondragón L, Orzáez M, Sancenón F, Martínez-Máñez R, Marcos MD, Amorós P, Pérez-Payá E (2014) Temperature-controlled release by changes in the secondary structure of peptides anchored onto mesoporous silica supports. Chem Commun 50(24):3184–3186

    Article  Google Scholar 

  • Tremmel M, Matzke A, Albrecht I, Laib AM, Olaku V, Ballmer-Hofer K, Christofori G, Héroult M, Augustin HG, Ponta H, Orian-Rousseau V (2009) A cd44v6 peptide reveals a role of cd44 in vegfr-2 signaling and angiogenesis. Blood 114(25):5236–5244

    Article  CAS  Google Scholar 

  • Verrier S, Pallu S, Bareille R, Jonczyk A, Meyer J, Dard M, Amédée J (2002) Function of linear and cyclic rgd-containing peptides in osteoprogenitor cells adhesion process. Biomaterials 23(2):585–596

    Article  CAS  Google Scholar 

  • Vivero-Escoto JL, Slowing II, Wu C-W, Lin VSY (2009) Photoinduced intracellular controlled release drug delivery in human cells by gold-capped mesoporous silica nanosphere. J Am Chem Soc 131(10):3462–3463

    Article  CAS  Google Scholar 

  • Vivero-Escoto JL, Slowing II, Trewyn BG, Lin VSY (2010) Mesoporous silica nanoparticles for intracellular controlled drug delivery. Small 6(18):1952–1967

    Article  CAS  Google Scholar 

  • 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(19):6024–6045

    Article  CAS  Google Scholar 

  • Zhang J, Yuan Z-F, Wang Y, Chen W-H, Luo G-F, Cheng S-X, Zhuo R-X, Zhang X-Z (2013) Multifunctional envelope-type mesoporous silica nanoparticles for tumor-triggered targeting drug delivery. J Am Chem Soc 135(13):5068–5073

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) (NRF-2020R1A2C1013219, NRF-2021R1C1C2011651). C.K. also thanks Inha University for support.

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Author notes

  1. Jeonghun Lee

    Present address: Department of Polymer Science and Engineering, Inha University, Incheon, 22212, Korea

Authors and Affiliations

  1. Department of Polymer Science and Engineering, Inha University, Incheon, 22212, Korea

    Chulhee Kim

  2. Program in Environmental and Polymer Engineering, Inha University, Incheon, 22212, Korea

    Jinhyeok Kim & Chulhee Kim

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  1. Jeonghun Lee
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Correspondence to Chulhee Kim.

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Lee, J., Kim, J. & Kim, C. Mesoporous silica nanoparticles with cyclic peptide gatekeeper for stimulus-responsive drug release by conformational transformation. J Nanopart Res 24, 22 (2022). https://doi.org/10.1007/s11051-022-05400-y

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