Skip to main content
SpringerLink
Log in

Targeting CD133+ laryngeal carcinoma cells with chemotherapeutic drugs and siRNA against ABCG2 mediated by thermo/pH-sensitive mesoporous silica nanoparticles

  • Original Article
  • Published:
Tumor Biology

Abstract

Mesoporous silica nanoparticles (MSNs) represent a new form of drug nanocarrier with thermo/pH-coupling sensitivity and site-specificity. CD133+ Hep-2 laryngeal cancer cells are responsible for multidrug resistance due to elevated expression of ABCG2. Since positively charged nanoparticles could easily uptake nucleic acids, we examined the possibility of using this new drug delivery system to simultaneously deliver different chemotherapeutic drugs and siRNA targeting ABCG2. Our results demonstrated that both antitumor drugs and siRNA against ABCG2 were successfully delivered into CD133+ cancer cells by loaded MSNs. Down-regulation of ABCG2 significantly enhanced the efficacy of chemotherapeutic drug-induced apoptosis in laryngeal carcinoma cells. Furthermore, the chemotherapeutic drug and siRNA loaded nanoparticles inhibited tumor growth in vivo in a laryngeal cancer mouse model.

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

Similar content being viewed by others

References

  1. Abdelmawla S, Guo S, Zhang L, Pulukuri SM, Patankar P, Conley P, et al. Pharmacological characterization of chemically synthesized monomeric phi29 pRNA nanoparticles for systemic delivery. Mol Ther. 2011;19(7):1312–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Agarwal A, Saraf S, Asthana A, Gupta U, Gajbhiye V, Jain NK. Ligand based dendritic systems for tumor targeting. Int J Pharm. 2008;350(1–2):3–13.

    Article  CAS  PubMed  Google Scholar 

  3. Cabral H, Matsumoto Y, Mizuno K, Chen Q, Murakami M, Kimura M, et al. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat Nanotechnol. 2011;6(12):815–23.

    Article  CAS  PubMed  Google Scholar 

  4. Chen H, Zhao JY, Qian XC, Cheng ZY, Liu Y, Wang Z. RASAL1 attenuates gastric carcinogenesis in nude mice by blocking RAS/ERK signaling. Asian Pac J Cancer Prev. 2015;16(3):1077–82.

    Article  PubMed  Google Scholar 

  5. de Jonge-Peeters SD, Kuipers F, de Vries EG, Vellenga E. ABC transporter expression in hematopoietic stem cells and the role in AML drug resistance. Crit Rev Oncol Hematol. 2007;62(3):214–26.

    Article  PubMed  Google Scholar 

  6. Polgar O, Robey RW, Bates SE. ABCG2: structure, function and role in drug response. Expert Opin Drug Metab Toxicol. 2008;4(1):1–15.

    Article  CAS  PubMed  Google Scholar 

  7. Honjo Y, Hrycyna CA, Yan QW, Medina-Perez WY, Robey RW, van de Laar A, et al. Acquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells. Cancer Res. 2001;61(18):6635–9.

    CAS  PubMed  Google Scholar 

  8. Meyer zu Schwabedissen HE, Kroemer HK. In vitro and in vivo evidence for the importance of breast cancer resistance protein transporters (BCRP/MXR/ABCP/ABCG2). Handb Exp Pharmacol. 2011;(201):325–71.

  9. Yang JP, Liu Y, Zhong W, Yu D, Wen LJ, Jin CS. Chemoresistance of CD133+ cancer stem cells in laryngeal carcinoma. Chin Med J (Engl). 2011;124(7):1055–60.

    CAS  Google Scholar 

  10. Wu CP, Xie M, Zhou L, Tao L, Zhang M, Tian J. Cooperation of side population cells with CD133 to enrich cancer stem cells in a laryngeal cancer cell line. Head Neck. 2014;36(9):1279–87.

    Google Scholar 

  11. Mannelli G, Magnelli L, Deganello A, Busoni M, Meccariello G, Parrinello G, et al. Detection of putative stem cell markers, CD44/CD133, in primary and lymph node metastases in head and neck squamous cell carcinomas. A preliminary immunohistochemical and in vitro study. Clin Otolaryngol. 2015;40(4):312–20.

    Article  CAS  PubMed  Google Scholar 

  12. Chen K, Huang YH, Chen JL. Understaning and targeting cancer stem cells: therapeutic implications and challenges. Acta Pharmacol Sin. 2013;34(6):732–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Liu X, Yu D, Jin C, Song X, Cheng J, Zhao X, et al. A dual responsive targeted drug delivery system based on smart polymer coated mesoporous silica for laryngeal carcinoma treatment. New J Chem. 2014;38:4830–6.

    Article  CAS  Google Scholar 

  14. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.

    Article  CAS  PubMed  Google Scholar 

  15. Friend DS, Papahadjopoulos D, Debs RJ. Endocytosis and intracellular processing accompanying transfection mediated by cationic liposomes. Biochim Biophys Acta. 1996;1278(1):41–50.

    Article  PubMed  Google Scholar 

  16. Gary DJ, Lee H, Sharma R, Lee JS, Kim Y, Cui ZY, et al. Influence of nano-carrier architecture on in vitro siRNA delivery performance and in vivo biodistribution: polyplexes vs micelleplexes. ACS Nano. 2011;5(5):3493–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Haque F, Shu D, Shu Y, Shlyakhtenko LS, Rychahou PG, Evers BM, et al. Ultrastable synergistic tetravalent RNA nanoparticles for targeting to cancers. Nano Today. 2012;7(4):245–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hong SH, Minai-Tehrani A, Chang SH, Jiang HL, Lee S, Lee AY, et al. Knockdown of the sodium-dependent phosphate co-transporter 2b (NPT2b) suppresses lung tumorigenesis. PLoS One. 2013;8(10):e77121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lefebvre JL. Candidates for larynx preservation: the next step? Oncologist. 2010;15 Suppl 3:30–2.

    Article  PubMed  Google Scholar 

  20. Maignan M, Koch FX, Kraemer M, Lehodey B, Viglino D, Monnet MF, et al. Impact of laryngeal tube use on chest compression fraction during out-of-hospital cardiac arrest. A prospective alternate month study. Resuscitation. 2015.

  21. Molitoris BA, Dagher PC, Sandoval RM, Campos SB, Ashush H, Fridman E, et al. siRNA targeted to p53 attenuates ischemic and cisplatin-induced acute kidney injury. J Am Soc Nephrol. 2009;20(8):1754–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM. Targeting multidrug resistance in cancer. Nat Rev Drug Discov. 2006;5(3):219–34.

    Article  CAS  PubMed  Google Scholar 

  23. Priebsch A, Rompe F, Tonnies H, Kowalski P, Surowiak P, Stege A, et al. Complete reversal of ABCG2-depending atypical multidrug resistance by RNA interference in human carcinoma cells. Oligonucleotides. 2006;16(3):263–74.

    Article  CAS  PubMed  Google Scholar 

  24. Vinogradov S, Wei X. Cancer stem cells and drug resistance: the potential of nanomedicine. Nanomedicine (Lond). 2012;7(4):597–615.

    Article  CAS  Google Scholar 

  25. Xie J, Jin B, Li DW, Shen B, Cong N, Zhang TZ, et al. ABCG2 regulated by MAPK pathways is associated with cancer progression in laryngeal squamous cell carcinoma. Am J Cancer Res. 2014;4(6):698–709.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Rodrigo JP, Coca-Pelaz A, Suarez C. The current role of partial surgery as a strategy for functional preservation in laryngeal carcinoma. Acta Otorrinolaringol Esp. 2011;62(3):231–8.

    Article  PubMed  Google Scholar 

  27. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11.

    Article  CAS  PubMed  Google Scholar 

  28. Matsui W, Wang Q, Barber JP, Brennan S, Smith BD, Borrello I, et al. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res. 2008;6:190–7.

    Article  Google Scholar 

  29. Wei XD, Zhou L, Cheng L, Tian J, Jiang JJ, Maccallum J. In vivo investigation of CD133 as a putative marker of cancer stem cells in Hep-2 cell line. Head Neck. 2009;31(1):94–101.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang Q, Shi S, Yen Y, Brown J, Ta JQ, Le AD. A subpopulation of CD133(+) cancer stem-like cells characterized in human oral squamous cell carcinoma confer resistance to chemotherapy. Cancer Lett. 2010;289(2):151–60.

    Article  CAS  PubMed  Google Scholar 

  31. Pozzi V, Sartini D, Rocchetti R, Santarelli A, Rubini C, Morganti S, et al. Identification and characterization of cancer stem cells from head and neck squamous cell carcinoma cell lines. Cell Physiol Biochem. 2015;36(2):784–98.

    Article  CAS  PubMed  Google Scholar 

  32. Shapira A, Livney YD, Broxterman HJ, Assaraf YG. Nanomedicine for targeted cancer therapy: towards the overcoming of drug resistance. Drug Resist Updat. 2011;14(3):150–63.

    Article  CAS  PubMed  Google Scholar 

  33. Ahmed N, Fessi H, Elaissari A. Theranostic applications of nanoparticles in cancer. Drug Discov Today. 2012;17(17–18):928–34.

    Article  CAS  PubMed  Google Scholar 

  34. Liu C, Zhao G, Liu J, Ma N, Chivukula P, Perelman L, et al. Novel biodegradable lipid nano complex for siRNA delivery significantly improving the chemosensitivity of human colon cancer stem cells to paclitaxel. J Control Release. 2009;140(3):277–83.

    Article  CAS  PubMed  Google Scholar 

  35. Tang DG. Understanding cancer stem cell heterogeneity and plasticity. Cell Res. 2012;22(3):457–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Xie M, Zhang H, Xu Y, Liu T, Chen S, Wang J, et al. Expression of folate receptors in nasopharyngeal and laryngeal carcinoma and folate receptor-mediated endocytosis by molecular targeted nanomedicine. Int J Nanomedicine. 2013;8:2443–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Takabatake Y, Isaka Y, Mizui M, Kawachi H, Takahara S, Imai E. Chemically modified siRNA prolonged RNA interference in renal disease. Biochem Biophys Res Commun. 2007;363(2):432–7.

    Article  CAS  PubMed  Google Scholar 

  38. Tamura A, Nagasaki Y. Smart siRNA delivery systems based on polymeric nanoassemblies and nanoparticles. Nanomedicine (Lond). 2010;5(7):1089–102.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Mesoporous silica nanoparticles in this study were kindly provided by the State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University. This work is supported by the National Natural Science Foundation of China (No. 81572653) and Jilin Province Natural Science Foundation of China, No. 20130101151JC, and the Chinese Ministry of Education Projects of Doctoral New teachers, No. 20120061120092.

Conflicts of interest

None

Ethical approval

All applicable national guidelines for the care and use of animals were followed.

Author information

Authors and Affiliations

  1. Department of Otolaryngology Head and Neck Surgery, the Second Hospital, Jilin University, Changchun, 130041, China

    Xinmeng Qi, Dan Yu, Chunshun Jin, Xueshibojie Liu & Xue Zhao

  2. Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, 100021, China

    Bo Jia

  3. Department of Thoracic Surgery, the Second Hospital, Jilin University, Changchun, 130041, China

    Guangxin Zhang

Authors
  1. Xinmeng Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dan Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bo Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chunshun Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xueshibojie Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xue Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guangxin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Dan Yu or Chunshun Jin.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qi, X., Yu, D., Jia, B. et al. Targeting CD133+ laryngeal carcinoma cells with chemotherapeutic drugs and siRNA against ABCG2 mediated by thermo/pH-sensitive mesoporous silica nanoparticles. Tumor Biol. 37, 2209–2217 (2016). https://doi.org/10.1007/s13277-015-4007-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-4007-9

Keywords

Search

Navigation