Skip to main content
SpringerLink
Log in

cRGD-modified core–shell mesoporous silica@BSA nanoparticles for drug delivery

  • Original Paper
  • Published:
Polymer Bulletin Aims and scope Submit manuscript

Abstract

Nano core–shell drug carriers with high stability, low toxicity, and targeted drug delivery are significance for the delivery of anti-tumor drugs. In this study, Albumin from bovine serum (BSA), serving as a capping agent, was conjugated to MSNs via a cleavable disulfide bond to generate a redox-responsive nanocarrier (MSNs@BSA). Subsequently, cRGD peptide, as a targeting ligand, was modified on the particle surface by a protein cross-linker to obtain nanoparticles with tumor cell-targeting properties (RGD-MSNs@BSA). The construction of RGD-MSNs@BSA was confirmed by DLS analysis, scanning electron microscope (SEM), transmission electron microscopy (TEM), electron dispersive spectroscopy (EDS), X-Ray Diffraction (XRD), and Fourier Transform Infrared Spectroscopy (FTIR), respectively. It was displayed that the model anticancer drug doxorubicin (DOX) was efficiently and stably encapsulated in RGD-MSNs@BSA in the absence of glutathione (GSH), and an outbreak of DOX was observed when the particles were exposed to a GSH-containing environment. It demonstrated that disulfide-linked BSA capping can increase the drug loading stability, while enduing it redox sensitivity. Flow cytometry and fluorescence microscope tests displayed that cellular uptake of RGD-MSNs@BSA was much higher than that of particles without cRGD and free DOX. These results indicated that RGD-MSNs@BSA can increase drug tumor-targeting and drug cellular uptake.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Maity AR, Stepensky D (2016) Limited efficiency of drug delivery to specific intracellular organelles using subcellularly “targeted” drug delivery systems. Mol Pharm 13(1):1–7

    Article  CAS  PubMed  Google Scholar 

  2. Zhao H, Feng H, Liu D, Liu J, Ji N, Chen F, Luo X, Zhou Y, Dan H, Zeng X, Li J, Sun C, Meng J, Ju X, Zhou M, Yang H, Li L, Liang X, Chu L, Jiang L, He Y, Chen Q (2015) Self-assembling monomeric nucleoside molecular nanoparticles loaded with 5-FU enhancing therapeutic efficacy against oral cancer. ACS Nano 9(10):9638–9651

    Article  CAS  PubMed  Google Scholar 

  3. Buehler DC, Marsden MD, Shen S, Toso DB, Wu X, Loo JA, Zhou ZH, Kickhoefer VA, Wender PA, Zack JA, Rome LH (2014) Bioengineered vaults: self-assembling protein shell-lipophilic core nanoparticles for drug delivery. ACS Nano 8(8):7723–7732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Peng L, Liu S, Feng A, Yuan J (2017) Polymeric nanocarriers based on cyclodextrins for drug delivery: host-guest interaction as stimuli responsive linker. Mol Pharm 14(8):2475–2486

    Article  CAS  PubMed  Google Scholar 

  5. Lu J, Liong M, Li Z, Zink JI, Tamanoi F (2010) Biocompatibility, biodistribution, and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals. Small 6(16):1794–1805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pan J, Wu R, Dai X, Yin Y, Pan G, Meng M, Shi W, Yan Y (2015) A hierarchical porous bowl-like PLA@MSNs-COOH composite for ph-dominated long-term controlled release of doxorubicin and integrated nanoparticle for potential second treatment. Biomacromol 16(4):1131–1145

    Article  CAS  Google Scholar 

  7. Cheng W, Nie J, Xu L, Liang C, Peng Y, Liu G, Wang T, Mei L, Huang L, Zeng X (2017) pH-sensitive delivery vehicle based on folic acid-conjugated polydopamine-modified mesoporous silica nanoparticles for targeted cancer therapy. ACS Appl Mater Interfaces 9(22):18462

    Article  CAS  PubMed  Google Scholar 

  8. Liu YL, Wu YH, Tsai WB, Tsai CC, Chen WS, Wu CS (2011) Core–shell silica@chitosan nanoparticles and hollow chitosan nanospheres using silica nanoparticles as templates: preparation and ultrasound bubble application. Carbohyd Polym 84(2):770–774

    Article  CAS  Google Scholar 

  9. Giménez C, ITC De, Gorbe M, Aznar E, Sancenón F, Murguía JR, Martínez-Máñez R, Marcos MD, Amorós P (2015) Gated mesoporous silica nanoparticles for the controlled delivery of drugs in cancer cells. Langmuir Acs J Surf Colloids 31(12): 3753

  10. Zhang B, Luo Z, Liu J, Ding X, Li J, Cai K (2014) Cytochrome c end-capped mesoporous silica nanoparticles as redox-responsive drug delivery vehicles for liver tumor-targeted triplex therapy in vitro and in vivo. J Control Release 192(7):192–201

    Article  CAS  PubMed  Google Scholar 

  11. Cheng Y, Zhang AQ, Hu JJ, He F, Zeng X, Zhang XZ (2017) Multifunctional peptide-amphiphile end-capped mesoporous silica nanoparticles for tumor targeting drug delivery. Acs Appl Mater Interfaces 9(3):2093–2103

    Article  CAS  PubMed  Google Scholar 

  12. Hu C, Huang P, Zheng Z, Yang Z, Wang X (2017) A facile strategy to prepare an enzyme-responsive mussel mimetic coating for drug delivery based on mesoporous silica nanoparticles. Langmuir 33(22):5511–5518

    Article  CAS  PubMed  Google Scholar 

  13. Yang Y, Lin Y, Di D, Zhang X, Wang D, Zhao Q, Wang S (2017) Gold nanoparticle-gated mesoporous silica as redox-triggered drug delivery for chemo-photothermal synergistic therapy. J Colloid Interface Sci 508:323–331

    Article  CAS  PubMed  Google Scholar 

  14. Park K, Park SS, Yun YH, Ha CS (2017) Mesoporous silica nanoparticles functionalized with a redox-responsive biopolymer. J Porous Mater 24(5):1–11

    Article  Google Scholar 

  15. Sun JT, Piao JG, Wang LH, Javed M, Hong CY, Pan CY (2013) One-pot synthesis of redox-responsive polymers-coated mesoporous silica nanoparticles and their controlled drug release. Macromol Rapid Commun 34(17):1387–1394

    Article  CAS  PubMed  Google Scholar 

  16. Yu L, Chen Y, Lin H, Du W, Chen H, Shi J (2018) Ultrasmall mesoporous organosilica nanoparticles: morphology modulations and redox-responsive biodegradability for tumor-specific drug delivery. Biomaterials 161:292–305

    Article  CAS  PubMed  Google Scholar 

  17. Thirupathi KRS, Prakash T, Gnanamani A (2017) Redox responsive albumin autogenic nanoparticles for the delivery of cancer drugs. Colloids Surf B 152:393

    Article  Google Scholar 

  18. Lin JT, Du JK, Yang YQ, Li L, Zhang DW, Liang CL, Wang J, Mei J, Wang GH (2017) pH and redox dual stimulate-responsive nanocarriers based on hyaluronic acid coated mesoporous silica for targeted drug delivery. Mater Sci Eng C 81:478

    Article  CAS  Google Scholar 

  19. Iyer AK, Khaled G, Fang J, Maeda H (2006) Exploiting the enhanced permeability and retention effect for tumor targeting. Drug Discov Today 11(17):812–818

    Article  CAS  PubMed  Google Scholar 

  20. Choi DS, Jin HE, Yoo SY, Lee SW (2014) Cyclic RGD peptide incorporation on phage major coat proteins for improved internalization by HeLa cells. Bioconjug Chem 25(2):216

    Article  CAS  PubMed  Google Scholar 

  21. Sun YX, Zeng X, Meng QF, Zhang XZ, Cheng SX, Zhuo RX (2008) The influence of RGD addition on the gene transfer characteristics of disulfide-containing polyethyleneimine/DNA complexes. Biomaterials 29(32):4356–4365

    Article  CAS  PubMed  Google Scholar 

  22. Estelrich J, Busquets MA, Morán MDC (2017) Effect of PEGylation on ligand-targeted magnetoliposomes: a missed goal. ACS Omega 2(10):6544–6555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Xu F, Liu J, Tian J, Gao L, Cheng X, Pan Y, Sun Z, Li X (2016) Supramolecular self-assemblies with nanoscale RGD clusters promote cell growth and intracellular drug delivery. ACS Appl Mater Interfaces 8(44):29906

    Article  CAS  PubMed  Google Scholar 

  24. Hao N, Liu H, Li L, Chen D, Li L, Tang F (2012) In vitro degradation behavior of silica nanoparticles under physiological conditions. J Nanosci Nanotechnol 12(8):6346

    Article  CAS  PubMed  Google Scholar 

  25. Kosmulski M (2002) The pH-dependent surface charging and the points of zero charge. J Colloid Interface Sci 253(1):77–87

    Article  CAS  PubMed  Google Scholar 

  26. Winiewska M, Szewczuk-Karpisz K, Sternik D (2015) Adsorption and thermal properties of the bovine serum albumin–silicon dioxide system. J Therm Anal Calorim 120(2):1355–1364

    Article  Google Scholar 

  27. Sah BK, Das K, Kundu S (2019) pH-dependent structure, pattern and hysteresis behaviour of lipid (DMPA)-protein (BSA) monolayer complex. Colloids Surf A Physicochem Eng Asp 579:123663

    Article  CAS  Google Scholar 

  28. Wang B, Zhou Y, Li L, Wang Y (2018) Preparation of amidoxime-functionalized mesoporous silica nanospheres (ami-MSN) from coal fly ash for the removal of U(VI). Sci Total Environ 626:219–227

    Article  CAS  PubMed  Google Scholar 

  29. Barman SC, Hossain MF, Yoon H, Park JY (2018) Trimetallic Pd@Au@Pt nanocomposites platform on –COOH terminated reduced graphene oxide for highly sensitive CEA and PSA biomarkers detection. Biosens Bioelectron 100:16–22

    Article  CAS  PubMed  Google Scholar 

  30. Yu J, Wang G, Wang X, Xu Y, Chen S, Wang X, Jiang L (2018) Improving the freeze-thaw stability of soy protein emulsions via combing limited hydrolysis and Maillard-induced glycation. LWT 91:63–69

    Article  CAS  Google Scholar 

  31. Das G, Nicastri A, Coluccio ML, Gentile F, Candeloro P, Cojoc G, Liberale C, De AF, Di FE (2010) FT-IR, Raman, RRS measurements and DFT calculation for doxorubicin. Microsc Res Tech 73(10):991–995

    CAS  PubMed  Google Scholar 

  32. Yaghoubi A, Ramazani A (2020) Anticancer DOX delivery system based on CNTs: functionalization, targeting and novel technologies. J Control Release 327:198–224

    Article  CAS  PubMed  Google Scholar 

  33. Dai L, Liu M, Long W, Hu X, Ouyang H, Feng Y, Deng F, Wen Y, Zhang X, Wei Y (2021) Synthesis of water dispersible and biocompatible nanodiamond composite via photocatalytic surface grafting of zwitterionic polymers for intracellular delivery of DOX. Mater Today Commun 103010

  34. Such GK, Yan Y, Johnston A, Gunawan ST, Caruso F (2015) Interfacing materials science and biology for drug carrier design. Adv Mater 27(14):2278–2297

    Article  CAS  PubMed  Google Scholar 

  35. Lili Y, Ruihua M, Li L, Fei L, Li S (2016) Intracellular Doxorubicin delivery of a core cross-linked, redox-responsive polymeric micelles. Int J Pharm 498(1–2):195–204

    Article  PubMed  Google Scholar 

  36. Yi Y, Kim HJ, Mi P, Zheng M, Takemoto H, Toh K, Kim BS, Hayashi K, Naito M, Matsumoto Y (2016) Targeted systemic delivery of siRNA to cervical cancer model using cyclic RGD-installed unimer polyion complex-assembled gold nanoparticles. J Control Release 244(Pt B):247

    Article  CAS  PubMed  Google Scholar 

  37. Wu D, Zhang Y, Xu X, Guo T, Xie D, Zhu R, Chen S, Ramakrishna S, He L (2018) RGD/TAT-functionalized chitosan-graft-PEI-PEG gene nanovector for sustained delivery of NT-3 for potential application in neural regeneration. Acta Biomater 72:266–277

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was financially supported by the Key Research and Development Program of Shaanxi (No. 2021ZDLSF03-05), Scientific and Technological Innovation Team of Xi’an Medical College (2021DT07), Xi’an Medical University Young Outstanding Talents Supporting Fund (05041905), Shaanxi Higher Education Research Project (XGH19042), Xi’an Science and Technology Plan Project (2020KJRC0135), and Xi’an Weiyang District Science and Technology Plan Project (201930).

Author information

Authors and Affiliations

  1. College of Pharmacy, Xi’an Medical University, Xi’an, 710021, Shaanxi, China

    Lili Yu, Kuan Yang, Wenling Fei, Qingqing Chen, Lan Qin, Shaojing Liu, Min Cao, Qian Liu & Bei Qin

  2. Institute of Medicine, Xi’an Medical University, Xi’an, 710021, shaanxi, China

    Lili Yu, Lin Yao, Kuan Yang, Wenling Fei, Shaojing Liu, Qian Liu & Bei Qin

  3. Shaanxi Key Laboratory of Chemical Additives for Industry, Shaanxi University of Science and Technology, Xi’an, 710021, Shannxi, China

    Lin Yao

  4. School of Pharmacy, Chengdu Medical College, Chengdu, 610500, Sichuan, China

    Qingqing Chen & Lan Qin

Authors
  1. Lili Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lin Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kuan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenling Fei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qingqing Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lan Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shaojing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Min Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Qian Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Bei Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bei Qin.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 408 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, L., Yao, L., Yang, K. et al. cRGD-modified core–shell mesoporous silica@BSA nanoparticles for drug delivery. Polym. Bull. 79, 10555–10571 (2022). https://doi.org/10.1007/s00289-021-03999-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00289-021-03999-x

Keywords

Search

Navigation