Skip to main content
SpringerLink
Log in

Nanocomposite pastes of gelatin and cyclodextrin-grafted chitosan nanoparticles as potential postoperative tumor therapy

  • Research
  • Published:
Advanced Composites and Hybrid Materials Aims and scope Submit manuscript

Abstract

Effective postoperative therapy is crucial for preventing tumor recurrence and metastasis. Nanocomposite (NC) pastes of Gel/CS-g-CD NP with unique viscoelastic properties and pH-responsive drug delivery ability were prepared from gelatin (Gel) and β-cyclodextrin-grafted chitosan nanoparticles (CS-g-CD NPs) through host–guest interactions between the aromatic amino acid residues of gelatin and β-cyclodextrin. The dynamic rheological properties, shear strength, and shear viscosity were modulated through variations in the concentration of CS-g-CD NPs in the NC pastes. Due to the reversibility of the host–guest interactions, the NC pastes exhibited shear-thinning and self-healing properties, endowing them with good injectability. Loading of doxorubicin (DOX) in the nanoparticles (DOX-CSCD NPs) forming the NC pastes of Gel/DOX-CSCD NP allowed pH-triggered DOX release in a simulated tumoral microenvironment, because of the labile nature of the CS-g-CD NPs under acidic conditions. In vitro experiments showed that the NC pastes of Gel/DOX-CSCD NP induced sustained tumor cell inhibition. Moreover, in vivo studies with tumor-bearing mice indicated that the NC pastes of Gel/DOX-CSCD NP can effectively inhibit tumor recurrence after surgical resection. Therefore, the NC pastes described in this work may act as an effective injectable drug delivery system for postoperative tumoral treatment.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data Availability

Data in this study will be made available when requested.

References

  1. Ingels A, Campi R, Capitanio U, Amparore D, Bertolo R, Carbonara U, de la Taille A (2022) Complementary roles of surgery and systemic treatment in clear cell renal cell carcinoma. Nat Rev Urol. https://doi.org/10.1038/s41585-022-00592-3

    Article  Google Scholar 

  2. Aquib M, Juthi AZ, Farooq MA, Ali MG, Janabi AHW, Bavi S, Wang B (2020) Advances in local and systemic drug delivery systems for post-surgical cancer treatment. Journal of Materials Chemistry B 8(37):8507–8518. https://doi.org/10.1039/D0TB00987C

    Article  CAS  Google Scholar 

  3. Li Z, Ding Y, Liu J, Wang J, Mo F, Wang Y, Hu Q (2022) Depletion of tumor associated macrophages enhances local and systemic platelet-mediated anti-PD-1 delivery for post-surgery tumor recurrence treatment. Nat Commun 13(1):1–15. https://doi.org/10.1038/s41467-022-29388-0

    Article  CAS  Google Scholar 

  4. Lu Y, Wu C, Yang Y, Chen X, Ge F, Wang J, Deng J (2022) Inhibition of tumor recurrence and metastasis via a surgical tumor-derived personalized hydrogel vaccine. Biomater Sci 10(5):1352–1363. https://doi.org/10.1039/D1BM01596F

    Article  CAS  Google Scholar 

  5. Ong BY, Ranganath SH, Lee LY, Lu F, Lee HS, Sahinidis NV, Wang CH (2009) Paclitaxel delivery from PLGA foams for controlled release in post-surgical chemotherapy against glioblastoma multiforme. Biomaterials 30(18):3189–3196. https://doi.org/10.1016/j.biomaterials.2009.02.030

    Article  CAS  Google Scholar 

  6. Chen Q, Wang C, Zhang X, Chen G, Hu Q, Li H, Gu Z (2019) In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment. Nat Nanotechnol 14(1):89–97. https://doi.org/10.1038/s41565-018-0319-4

    Article  CAS  Google Scholar 

  7. Bastiancich C, Malfanti A, Préat V, Rahman R (2021) Rationally designed drug delivery systems for the local treatment of resected glioblastoma. Adv Drug Deliv Rev 177:113951. https://doi.org/10.1016/j.addr.2021.113951

    Article  CAS  Google Scholar 

  8. Mazidi Z, Javanmardi S, Naghib SM, Mohammadpour Z (2022) Smart stimuli-responsive implantable drug delivery systems for programmed and on-demand cancer treatment: an overview on the emerging materials. Chem Eng J. https://doi.org/10.1016/j.cej.2022.134569

    Article  Google Scholar 

  9. Wang C, Sun W, Wright G, Wang AZ, Gu Z (2016) Inflammation-triggered cancer immunotherapy by programmed delivery of CpG and anti-PD1 antibody. Adv Mater 28(40):8912–8920. https://doi.org/10.1002/adma.201506312

    Article  CAS  Google Scholar 

  10. Merino S, Martín C, Kostarelos K, Prato M, Vázquez E (2015) Nanocomposite hydrogels: 3D polymer–nanoparticle synergies for on-demand drug delivery. ACS Nano 9(5):4686–4697. https://doi.org/10.1021/acsnano.5b01433

    Article  CAS  Google Scholar 

  11. Huang S, Hong X, Zhao M, Liu N, Liu H, Zhao J, Guo R (2022) Nanocomposite hydrogels for biomedical applications. Bioeng Transl Med e10315. https://doi.org/10.1002/btm2.10315

  12. Lavrador P, Esteves MR, Gaspar VM, Mano JF (2021) Stimuli-responsive nanocomposite hydrogels for biomedical applications. Adv Func Mater 31(8):2005941. https://doi.org/10.1002/adfm.202005941

    Article  CAS  Google Scholar 

  13. Liu X, Chen X, Chua MX, Li Z, Loh XJ, Wu YL (2017) Injectable supramolecular hydrogels as delivery agents of Bcl-2 conversion gene for the effective shrinkage of therapeutic resistance tumors. Adv Healthcare Mater 6(11):1700159. https://doi.org/10.1002/adhm.201700159

    Article  CAS  Google Scholar 

  14. Zhang J, Chen C, Li A, Jing W, Sun P, Huang X, Jiang X (2021) Immunostimulant hydrogel for the inhibition of malignant glioma relapse post-resection. Nat Nanotechnol 16(5):538–548. https://doi.org/10.1038/s41565-020-00843-7

    Article  CAS  Google Scholar 

  15. Huang H, Wang X, Wang W, Qu X, Song X, Zhang Y, Zhao Y (2022) Injectable hydrogel for postoperative synergistic photothermal-chemodynamic tumor and anti-infection therapy. Biomaterials 280:121289. https://doi.org/10.1016/j.biomaterials.2021.121289

    Article  CAS  Google Scholar 

  16. Du W, Zong Q, Guo R, Ling G, Zhang P (2021) Injectable nanocomposite hydrogels for cancer therapy. Macromol Biosci 21(11):2100186. https://doi.org/10.1002/mabi.202100186

    Article  CAS  Google Scholar 

  17. Zhang Y, Jiang C (2021) Postoperative cancer treatments: in-situ delivery system designed on demand. J Control Release 330:554–564. https://doi.org/10.1016/j.jconrel.2020.12.038

    Article  CAS  Google Scholar 

  18. Cao S, Li L, Du Y, Gan J, Wang J, Wang T Liu T (2021) Porous gelatin microspheres for controlled drug delivery with high hemostatic efficacy. Colloids Surf B 207:112013. https://doi.org/10.1016/j.colsurfb.2021.112013

    Article  CAS  Google Scholar 

  19. Garg U, Chauhan S, Nagaich U, Jain N (2019) Current advances in chitosan nanoparticles based drug delivery and targeting. Adv Pharm Bull 9(2), 195–204. https://apb.tbzmed.ac.ir/Article/apb-23086

  20. Tian B, Liu Y, Liu J (2021) Smart stimuli-responsive drug delivery systems based on cyclodextrin: a review. Carbohyd Polym 251:116871. https://doi.org/10.1016/j.carbpol.2020.116871

    Article  CAS  Google Scholar 

  21. Song M, Li L, Zhang Y, Chen K, Wang H, Gong R (2017) Carboxymethyl-β-cyclodextrin grafted chitosan nanoparticles as oral delivery carrier of protein drugs. React Funct Polym 117:10–15. https://doi.org/10.1016/j.reactfunctpolym.2017.05.008

    Article  CAS  Google Scholar 

  22. Yu N, Li G, Gao Y, Liu X, Ma S (2016) Stimuli-sensitive hollow spheres from chitosan-graft-β-cyclodextrin for controlled drug release. Int J Biol Macromol 93:971–977. https://doi.org/10.1016/j.ijbiomac.2016.09.068

    Article  CAS  Google Scholar 

  23. KC, R. B., Lee, S. M., Yoo, E. S., Choi, J. H., & Do Ghim, H. (2009) Glycoconjugated chitosan stabilized iron oxide nanoparticles as a multifunctional nanoprobe. Mater Sci Eng, C 29(5):1668–1673. https://doi.org/10.1016/j.msec.2009.01.005

    Article  CAS  Google Scholar 

  24. Feng Q, Wei K, Lin S, Xu Z, Sun Y, Shi P, Bian L (2016) Mechanically resilient, injectable, and bioadhesive supramolecular gelatin hydrogels crosslinked by weak host-guest interactions assist cell infiltration and in situ tissue regeneration. Biomaterials 101:217–228. https://doi.org/10.1016/j.biomaterials.2016.05.043

    Article  CAS  Google Scholar 

  25. Neuhaus D, Williamson MP (1989) The nuclear overhauser effect in structural and conformational analysis. Wiley-VCH, New York. https://doi.org/10.1002/mrc.1260280819

    Book  Google Scholar 

  26. Winter HH, Chambon F (1986) Analysis of linear viscoelasticity of a crosslinking polymer at the gel point. J Rheol 30(2):367–382. https://doi.org/10.1122/1.549853

    Article  CAS  Google Scholar 

  27. Wu SC, Chang WH, Dong GC, Chen KY, Chen YS, Yao CH (2011) Cell adhesion and proliferation enhancement by gelatin nanofiber scaffolds. J Bioact Compat Polym 26(6):565–577. https://doi.org/10.1177/0883911511423563

    Article  CAS  Google Scholar 

  28. Huo M, Zou A, Yao C, Zhang Y, Zhou J, Wang J, Zhang Q (2012) Somatostatin receptor-mediated tumor-targeting drug delivery using octreotide-PEG-deoxycholic acid conjugate-modified N-deoxycholic acid-O. N-hydroxyethylation chitosan micelles Biomaterials 33(27):6393–6407. https://doi.org/10.1016/j.biomaterials.2012.05.052

    Article  CAS  Google Scholar 

  29. Xiao L, Huang L, Moingeon F, Gauthier M, Yang G (2017) pH-responsive poly (ethylene glycol)-block-polylactide micelles for tumor-targeted drug delivery. Biomacromol 18(9):2711–2722. https://doi.org/10.1021/acs.biomac.7b00509

    Article  CAS  Google Scholar 

  30. Zheng S, Jin Z, Han J, Cho S, Ko SY, Park JO, Park S (2016) Preparation of HIFU-triggered tumor-targeted hyaluronic acid micelles for controlled drug release and enhanced cellular uptake. Colloids Surf, B 143:27–36. https://doi.org/10.1016/j.colsurfb.2016.03.019

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (Nos. 52173151, 51803067, 51973076), Hubei Provincial Natural Science Foundation (2020CFB491), Science Research Program of the Education Department of Hubei Province (Q20203002), and the open foundation of Hubei Key Laboratory of Theory and Application of Advanced Materials Mechanics (Wuhan University of Technology) (No.: TAM202006).

Author information

Authors and Affiliations

  1. School of Biomedical Engineering, Shenzhen Campus, Sun Yat-Sen University, Shenzhen, 518107, China

    Lin Xiao & Weichang Xu

  2. Hubei Key Laboratory of Purification and Application of Plant Anti-Cancer Active Ingredients, School of Chemistry and Life Sciences, Hubei University of Education, Wuhan, 430205, China

    Lixia Huang

  3. Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China

    Lixia Huang & Guang Yang

  4. Hubei Key Laboratory of Theory and Application of Advanced Materials Mechanics, Wuhan University of Technology, Wuhan, 430070, China

    Jili Liu

Authors
  1. Lin Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weichang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lixia Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jili Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Lin Xiao, Guang Yang, and Lixia Huang designed the work and provided funding support. Lin Xiao, Lixia Huang, and Weichang Xu conducted the investigation, analysis, and validation. Lin Xiao and Lixia Huang prepared the original draft manuscript. Jili Liu participated in the data analysis and edited the manuscript. Guang Yang directed the investigation and edited the manuscript. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Lixia Huang or Guang Yang.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

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 file (DOCX 3750 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiao, L., Xu, W., Huang, L. et al. Nanocomposite pastes of gelatin and cyclodextrin-grafted chitosan nanoparticles as potential postoperative tumor therapy. Adv Compos Hybrid Mater 6, 15 (2023). https://doi.org/10.1007/s42114-022-00575-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s42114-022-00575-3

Keywords

Search

Navigation