Skip to main content

Advertisement

SpringerLink
Log in

Imaging Fast Cellular Uptake of Polymer Dots via Receptor-Mediated Endocytosis

  • Original Paper
  • Published:
Journal of Analysis and Testing Aims and scope Submit manuscript

Abstract

During the past decade, semiconducting polymer dots (Pdots) have been prevailing in the family of fluorescent probes due to its high photon budget, excellent photo stability, and good biocompatibility. In this study, holo-Transferrin human (Tf) was utilized to covalently couple with Pdots for a highly efficient endocytosis process through transferrin receptors (TfRs) mediated internalization. As a result, the endocytosis efficiency of Tf-conjugated Pdots in HeLa cells dramatically increased as compared to that of unconjugated Pdots in the same condition. This acute increment demonstrates that holo-Transferrin molecules are of great capability for intracellular delivery of Pdots to TfRs overexpressed cells. The transportation route of Tf-conjugated Pdots is quite different from the uptake mechanism of unconjugated Pdots via nonspecific endocytic trafficking pathway. Considering the overexpression of TfRs in various cancer cells, Tf-conjugated Pdots hold potential to function as a nanocarrier for efficient drug delivery in cancer diagnostics and therapy.

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

Similar content being viewed by others

References

  1. Huebers HA, Finch CA. The physiology of transferrin and transferrin receptors. Physiol Rev. 1987;67:520–82.

    Article  CAS  Google Scholar 

  2. Koechlin BA. Preparation and properties of serum and plasma proteins. J Am Chem Soc. 1952;74:2649–52.

    Article  CAS  Google Scholar 

  3. Andrews NC. Iron homeostasis: insights from genetics and animal models. Nat Rev Genet. 2000;1:208–17.

    Article  CAS  Google Scholar 

  4. Qian ZM, Tang PL. Mechanisms of iron uptake by mammalian cells. Biochem Biophys Acta. 1995;1269:205–14.

    Article  Google Scholar 

  5. Rothenberger SBI, Iacopetta BJ, Kühn LC. Endocytosis of the transferrin receptor requires the cytoplasmic domain but not its phosphorylation site. Cell. 1987;49:423–31.

    Article  CAS  Google Scholar 

  6. McGraw TE, Maxfield FR. Human transferrin receptor internalization is partly dependent upon an aromatic amino acid in the cytoplasmic domain. Cell Regul. 1990;1:369–77.

    CAS  Google Scholar 

  7. Mullner EW, Kuhn LC. A stem-loop in the 3’ untranslated region mediates iron-dependent regulation of transferrin receptor mRNA stability in the cytoplasm. Cell. 1988;53:815–25.

    Article  CAS  Google Scholar 

  8. Ponka P, Lok CN. The transferrin receptor: role in health and disease. Int J Biochem Cell Biol. 1999;31:1111–37.

    Article  CAS  Google Scholar 

  9. Sager PR, Brown PA, Berlin RD. Analysis of transferrin recycling in mitotic and interphase HeLa cells by quantitative fluorescence microscopy. Cell. 1984;39:275–82.

    Article  CAS  Google Scholar 

  10. Yoon DJ, Chu DS, Ng CW, Pham EA, Mason AB, Hudson DM, et al. Genetically engineering transferrin to improve its in vitro ability to deliver cytotoxins. J Control Release. 2009;133:178–84.

    Article  CAS  Google Scholar 

  11. Li H, Qian ZM. Transferrin/transferrin receptor-mediated drug delivery. Med Res Rev. 2002;22:225–50.

    Article  CAS  Google Scholar 

  12. Li H, Sun H, Qian ZM. The role of the transferrin-transferrin-receptor system in drug delivery and targeting. Trends Pharmacol Sci. 2002;23:206–9.

    Article  CAS  Google Scholar 

  13. Daniels TR, Bernabeu E, Rodriguez JA, Patel S, Kozman M, Chiappetta DA, et al. The transferrin receptor and the targeted delivery of therapeutic agents against cancer. Biochim Biophys Acta Gen Subj. 2012;1820:291–317.

    Article  CAS  Google Scholar 

  14. Bickel U, Yoshikawa T, Pardridge WM. Delivery of peptides and proteins through the blood-brain barrier. Adv Drug Deliv Rev. 2001;46:247–79.

    Article  CAS  Google Scholar 

  15. Pardridge WM. Blood-brain barrier drug targeting enables neuroprotection in brain ischemia following delayed intravenous administration of neurotrophins. Adv Exp Med Biol. 2002;513:397–430.

    Article  CAS  Google Scholar 

  16. Langer R. Drug delivery and targeting. Nature. 1998;392:5–10.

    CAS  Google Scholar 

  17. Maruyama K, Ishida O, Takizawa T, Moribe K. Possibility of active targeting to tumor tissues with liposomes. Adv Drug Deliv Rev. 1999;40:89–102.

    Article  CAS  Google Scholar 

  18. Vyas SP, Singh A, Sihorkar V. Ligand-receptor-mediated drug delivery: an emerging paradigm in cellular drug targeting. Crit Rev Ther Drug Carrier Syst. 2001;18:1–76.

    Article  CAS  Google Scholar 

  19. Cardoso AL, Simoes S, de Almeida LP, Plesnila N, de Lima Pedroso MC, Wagner E, et al. Tf-lipoplexes for neuronal siRNA delivery: a promising system to mediate gene silencing in the CNS. J Control Release. 2008;132:113–23.

    Article  CAS  Google Scholar 

  20. Zhai G, Wu J, Yu B, Guo C, Yang X, Lee RJ. A transferrin receptor-targeted liposomal formulation for docetaxel. J Nanosci Nanotechnol. 2010;10:5129–36.

    Article  CAS  Google Scholar 

  21. Dixit S, Novak T, Miller K, Zhu Y, Kenney ME, Broome AM. Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors. Nanoscale. 2015;7:1782–90.

    Article  CAS  Google Scholar 

  22. Wiley DT, Webster P, Gale A, Davis ME. Transcytosis and brain uptake of transferrin-containing nanoparticles by tuning avidity to transferrin receptor. Proc Natl Acad Sci USA. 2013;110:8662–7.

    Article  CAS  Google Scholar 

  23. Jing LH, Ding K, Kershaw SV, Kempson IM, Rogach AL, Gao MY. Magnetically engineered semiconductor quantum dots as multimodal imaging probes. Adv Mater. 2014;26:6367–86.

    Article  CAS  Google Scholar 

  24. Ding W, Guo L. Immobilized transferrin Fe3O4@SiO2 nanoparticle with high doxorubicin loading for dual-targeted tumor drug delivery. Int J Nanomed. 2013;8:4631–9.

    Google Scholar 

  25. Biju V, Itoh T, Ishikawa M. Delivering quantum dots to cells: bioconjugated quantum dots for targeted and nonspecific extracellular and intracellular imaging. Chem Soc Rev. 2010;39:3031–56.

    Article  CAS  Google Scholar 

  26. Cabral Filho PE, Cardoso AL, Pereira MI, Ramos AP, Hallwass F, Castro MM, et al. CdTe quantum dots as fluorescent probes to study transferrin receptors in glioblastoma cells. Biochim Biophys Acta Gen Subj. 2016;1860:28–35.

    Article  CAS  Google Scholar 

  27. Chen DN, Xu GX, Ali BA, Yong KT, Zhou CH, Wang XM, et al. Uptake of transferrin-conjugated quantum dots in single living cells. Chin Opt Lett. 2010;8:940–3.

    Article  CAS  Google Scholar 

  28. Schieber C, Bestetti A, Lim JP, Ryan AD, Nguyen TL, Eldridge R, et al. Conjugation of transferrin to azide-modified CdSe/ZnS core-shell quantum dots using cyclooctyne click chemistry. Angew Chem Int Edit. 2012;51:10523–7.

    Article  CAS  Google Scholar 

  29. Zhang MZ, Yu RN, Chen J, Ma ZY, Zhao YD. Targeted quantum dots fluorescence probes functionalized with aptamer and peptide for transferrin receptor on tumor cells. Nanotechnology. 2012;23:485104.

    Article  Google Scholar 

  30. Chang K, Tang Y, Fang X, Yin S, Xu H, Wu C. Incorporation of porphyrin to π-conjugated backbone for polymer-dot-sensitized photodynamic therapy. Biomacromol. 2016;17:2128–36.

    Article  CAS  Google Scholar 

  31. Chen X, Li R, Liu Z, Sun K, Sun Z, Chen D, et al. Small photoblinking semiconductor polymer dots for fluorescence nanoscopy. Adv Mater. 2017;29:1604850.

    Article  Google Scholar 

  32. Chen X, Liu Z, Li R, Shan C, Zeng Z, Xue B, et al. Multicolor super-resolution fluorescence microscopy with blue and carmine small photoblinking polymer dots. ACS Nano. 2017;11:8084–91.

    Article  CAS  Google Scholar 

  33. Sun K, Chen H, Wang L, Yin S, Wang H, Xu G, et al. Size-dependent property and cell labeling of semiconducting polymer dots. ACS Appl Mater Interfaces. 2014;6:10802–12.

    Article  CAS  Google Scholar 

  34. Sun K, Tang Y, Li Q, Yin S, Qin W, Yu J, et al. In vivo dynamic monitoring of small molecules with implantable polymer-dot transducer. ACS Nano. 2016;10:6769–81.

    Article  CAS  Google Scholar 

  35. Wu C, Chiu DT. Highly fluorescent semiconducting polymer dots for biology and medicine. Angew Chem. 2013;52:3086–109.

    Article  CAS  Google Scholar 

  36. Yu J, Wu C, Sahu SP, Fernando LP, Szymanski C, McNeill J. Nanoscale 3D tracking with conjugated polymer nanoparticles. J Am Chem Soc. 2009;131:18410–4.

    Article  CAS  Google Scholar 

  37. Wu C, Bull B, Szymanski C, Christensen K, McNeill J. Multicolor conjugated polymer dots for biological fluorescence imaging. ACS Nano. 2008;2:2415–23.

    Article  CAS  Google Scholar 

  38. Wu C, Szymanski C, McNeill J. Preparation and encapsulation of highly fluorescent conjugated polymer nanoparticles. Langmuir ACS J Surf Colloid. 2006;22:2956–60.

    Article  CAS  Google Scholar 

  39. Chithrani BD, Ghazani AA, Chan WCW. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 2006;6:662–8.

    Article  CAS  Google Scholar 

  40. Sulin Zhang Ju, Li George Lykotrafitis, Bao Gang, Suresh S. Size-dependent endocytosis of nanoparticles. Adv Mater. 2008;21:419–24.

    Article  Google Scholar 

  41. Sanjeeb K, Sahoo VL. Enhanced antiproliferative activity of transferrin-conjugated paclitaxel-loaded nanoparticles is mediated via sustained intracellular drug retention. Mol Pharm. 2005;2:373–83.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the grants from the National Natural Science Foundation of China (Grant Nos. 61335001; 81771930), and Shenzhen Science and Technology Innovation Commission (Grant No. JCYJ20170307110157501).

Author information

Authors and Affiliations

  1. State Key Laboratory of Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun, 130012, Jilin, China

    Zezhou Sun, Ye Yuan & Zhihe Liu

  2. Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, China

    Changfeng Wu

  3. Shandong Province Key Laboratory of Detection Technology for Tumor Markers, College of Chemistry and Chemical Engineering, Linyi University, Linyi, 276000, Shandong, China

    Qiong Li

Authors
  1. Zezhou Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ye Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhihe Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Changfeng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Changfeng Wu.

Ethics declarations

Conflict of Interest

The author(s) declare that they have no competing interests.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, Z., Yuan, Y., Li, Q. et al. Imaging Fast Cellular Uptake of Polymer Dots via Receptor-Mediated Endocytosis. J. Anal. Test. 2, 61–68 (2018). https://doi.org/10.1007/s41664-018-0048-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s41664-018-0048-6

Keywords

Search

Navigation