SpringerLink
Log in

Dual Targeting Drug Delivery for Cancer Theranostics

  • Chapter
  • First Online:
Cancer Nanotheranostics

Part of the book series: Nanotechnology in the Life Sciences ((NALIS))

  • 587 Accesses

Abstract

Over recent years, theranostic nanosystems have emerged as promising tools in cancer therapy and diagnostics. Active-targeted theranostic nanosystems are based on develo** a nanocarrier modified with ligands or particular physical or chemical characteristics for specifically bind to surface markers of cancer cells and deliver therapeutic imaging and diagnostic agent or all of them to specific cancer cells and even organelles, providing personalized treatment for different tumors and patients. To now, different ligands were used to active targeting of nanocarriers. Antibodies, aptamers, transferrin, folic acid, and arginine-glycine-aspartic acid tripeptide are of the most studied ligands used for active targeting. Cancerous cells can internalize these systems by receptor-mediated endocytosis. However, therapeutic efficacy of single-targeted developed drug delivery systems is not yet satisfactory for clinical use because of the tumors complex microenvironment. To address mentioned challenge, dual and multi-targeted therapies have developed recently and demonstrate superior efficacy over single targeting in terms of cellular uptake, cell selectivity, and penetration into the tumor. Several dual-targeted nanocarriers introduced for cancer theranostic mainly belong to lipid-, polymer-, and carbon-based carriers. Herein, an overview of various developed dual-targeted nanomedicines used for cancer targeted theranostic will be reviewed; also challenges and outlook in designing dual-targeted nanomedicines will be discussed. Although these studies are only conducted in vitro and in vivo, in the upcoming years, it is highly likely that this field of treatment and diagnostics will be used in the clinical stage and help better treatment of rare diseases including cancer.

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Abbreviations

BBB :

Blood-brain barrier

BPA :

Borono phenylalanine

BSH :

Sodium boro captate

c(RGDyC):

Cyclic arginine-glycine-aspartic acid-tyrosine-cysteine

CNT :

Carbon nanotubes

DOX :

Doxorubicin

EGFP :

Enhanced green fluorescent protein

EGFR :

Epidermal growth factor receptor

EPR :

Permeability and retention effect

FA :

Folate

FDA :

US Food and Drug Administration

GBM :

Glioblastoma multiforme

Glu-VC :

Glucose and vitamin C

GO :

Graphene oxide

HA :

Hyaluronic acid

HAP :

Hydroxyapatite

HepG2 :

Hepatocellular carcinoma cell line

HIV :

Human immunodeficiency virus

IL-4R :

Interleukin-4 receptor

MGO :

Magnetic graphene oxide

OA :

Oleanolic acid

O-MWNT :

Oxidized multi-walled carbon nanotube

PAMAM :

Poly(amidoamine)

PCL :

Poly(3-caprolactone)

PLA :

Polylactic acid

PLGA :

Polylactic-co-glycolic acid

PNAL :

Poly[(N isopropylacrylamide-r-acrylamide)-b-L-lactic acid]

PTX :

Paclitaxel

RAGE :

Receptors for advanced glycation end products

RGD :

Arginine-glycine-aspartic acid

Tf :

Transferrin

TfR :

Tf receptor

WGA :

Wheat germ agglutinin

References

  • Amoabediny, G., Haghiralsadat, F., Naderinezhad, S., Helder, M. N., Akhoundi Kharanaghi, E., Mohammadnejad Arough, J., & Zandieh-Doulabi, B. (2018a). Overview of preparation methods of polymeric and lipid-based (niosome, solid lipid, liposome) nanoparticles: A comprehensive review. International Journal of Polymeric Materials and Polymeric Biomaterials, 67(6), 383–400.

    Article  CAS  Google Scholar 

  • Amoabediny, G., Ochi, M. M., Rezayat, S. M., Akbarzadeh, A., & Ebrahimi, B. (2018b). Targeted nano-liposome co-entrap** anti-cancer drugs. Google patent US20160228362A1.

    Google Scholar 

  • Anarjan, F. S. (2019). Active targeting drug delivery nanocarriers: Ligands. Nano-Structures & Nano-Objects, 19, 100370.

    Article  CAS  Google Scholar 

  • Belfiore, L., Saunders, D. N., Ranson, M., Thurecht, K. J., Storm, G., & Vine, K. L. (2018). Towards clinical translation of ligand-functionalized liposomes in targeted cancer therapy: Challenges and opportunities. Journal of Controlled Release, 277, 1–13.

    Article  CAS  PubMed  Google Scholar 

  • Chen, D., Li, B., Cai, S., Wang, P., Peng, S., Sheng, Y., He, Y., Gu, Y., & Chen, H. (2016). Dual targeting luminescent gold nanoclusters for tumor imaging and deep tissue therapy. Biomaterials, 100, 1–16.

    Article  CAS  PubMed  Google Scholar 

  • Danhier, F., Feron, O., & Préat, V. (2010). To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. Journal of Controlled Release, 148(2), 135–146.

    Article  CAS  PubMed  Google Scholar 

  • Donahue, N. D., Acar, H., & Wilhelm, S. (2019). Concepts of nanoparticle cellular uptake, intracellular trafficking, and kinetics in nanomedicine. Advanced Drug Delivery Reviews, 143, 68–96.

    Article  CAS  PubMed  Google Scholar 

  • Du, J., Li, Q., Chen, L., Wang, S., Zhang, L., Yu, S., Yang, Y., & Liu, X. (2020). In vitro cytotoxicity and antitumor activity of dual-targeting drug delivery system based on modified magnetic carbon by folate. Journal of Nanomaterials, 2020, 1.

    Article  CAS  Google Scholar 

  • Gao, H., **ong, Y., Zhang, S., Yang, Z., Cao, S., & Jiang, X. (2014). RGD and interleukin-13 peptide functionalized nanoparticles for enhanced glioblastoma cells and neovasculature dual targeting delivery and elevated tumor penetration. Molecular Pharmaceutics, 11(3), 1042–1052.

    Article  CAS  PubMed  Google Scholar 

  • Haghiralsadat, F., Amoabediny, G., Naderinezhad, S., Zandieh-Doulabi, B., Forouzanfar, T., & Helder, M. N. (2018). Codelivery of doxorubicin and JIP1 siRNA with novel EphA2-targeted PEGylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance. International Journal of Nanomedicine, 13, 3853.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He, H., Li, Y., Jia, X.-R., Du, J., Ying, X., Lu, W.-L., Lou, J.-N., & Wei, Y. (2011). PEGylated poly (amidoamine) dendrimer-based dual-targeting carrier for treating brain tumors. Biomaterials, 32(2), 478–487.

    Article  CAS  PubMed  Google Scholar 

  • Huang, M., Pu, Y., Peng, Y., Fu, Q., Guo, L., Wu, Y., & Zheng, Y. (2020). Biotin and glucose dual-targeting, ligand-modified liposomes promote breast tumor-specific drug delivery. Bioorganic & Medicinal Chemistry Letters, 30(12), 127151.

    Article  CAS  Google Scholar 

  • Hussien, N. A., Işıklan, N., & Türk, M. (2018). Aptamer-functionalized magnetic graphene oxide nanocarrier for targeted drug delivery of paclitaxel. Materials Chemistry and Physics, 211, 479–488.

    Article  CAS  Google Scholar 

  • Kang, W., Svirskis, D., Saro**i, V., McGregor, A. L., Bevitt, J., & Wu, Z. (2017). Cyclic-RGDyC functionalized liposomes for dual-targeting of tumor vasculature and cancer cells in glioblastoma: An in vitro boron neutron capture therapy study. Oncotarget, 8(22), 36614.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ke, X., Lin, W., Li, X., Wang, H., **ao, X., & Guo, Z. (2017). Synergistic dual-modified liposome improves targeting and therapeutic efficacy of bone metastasis from breast cancer. Drug Delivery, 24(1), 1680–1689.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kluza, E., Jacobs, I., Hectors, S. J., Mayo, K. H., Griffioen, A. W., Strijkers, G. J., & Nicolay, K. (2012). Dual-targeting of αvβ3 and galectin-1 improves the specificity of paramagnetic/fluorescent liposomes to tumor endothelium in vivo. Journal of Controlled Release, 158(2), 207–214.

    Article  CAS  PubMed  Google Scholar 

  • Kydd, J., Jadia, R., Velpurisiva, P., Gad, A., Paliwal, S., & Rai, P. (2017). Targeting strategies for the combination treatment of cancer using drug delivery systems. Pharmaceutics, 9(4), 46.

    Article  PubMed Central  CAS  Google Scholar 

  • Lammers, T., Kiessling, F., Hennink, W. E., & Storm, G. (2012). Drug targeting to tumors: Principles, pitfalls and (pre-) clinical progress. Journal of Controlled Release, 161(2), 175–187.

    Article  CAS  PubMed  Google Scholar 

  • Li, R., Wu, R. A., Zhao, L., Hu, Z., Guo, S., Pan, X., & Zou, H. (2011). Folate and iron difunctionalized multiwall carbon nanotubes as dual-targeted drug nanocarrier to cancer cells. Carbon, 49(5), 1797–1805.

    Article  CAS  Google Scholar 

  • Li, J., Liang, X., Zhang, J., Yin, Y., Zuo, T., Wang, Y., Yang, X., & Shen, Q. (2018a). Inhibiting pulmonary metastasis of breast cancer based on dual-targeting graphene oxide with high stability and drug loading capacity. Nanomedicine: Nanotechnology, Biology and Medicine, 14(4), 1237–1248.

    Article  CAS  Google Scholar 

  • Li, L., Wang, Q., Zhang, X., Luo, L., He, Y., Zhu, R., & Gao, D. (2018b). Dual-targeting liposomes for enhanced anticancer effect in somatostatin receptor II-positive tumor model. Nanomedicine, 13(17), 2155–2169.

    Article  CAS  PubMed  Google Scholar 

  • Lin, M. M., Kang, Y. J., Sohn, Y., & Kim, D. K. (2015a). Dual targeting strategy of magnetic nanoparticle-loaded and RGD peptide-activated stimuli-sensitive polymeric micelles for delivery of paclitaxel. Journal of Nanoparticle Research, 17(6), 1–18.

    Article  CAS  Google Scholar 

  • Lin, M. M., Kang, Y. J., Sohn, Y., & Kim, D. K. (2015b). Dual targeting strategy of magnetic nanoparticle-loaded and RGD peptide-activated stimuli-sensitive polymeric micelles for delivery of paclitaxel. Journal of Nanoparticle Research, 17(6), 248.

    Article  CAS  Google Scholar 

  • Liu, G.-X., Fang, G.-Q., & Xu, W. (2014). Dual targeting biomimetic liposomes for paclitaxel/DNA combination cancer treatment. International Journal of Molecular Sciences, 15(9), 15287–15303.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu, Y., Chen, Q., Xu, M., Guan, G., Hu, W., Liang, Y., Zhao, X., Qiao, M., Chen, D., & Liu, H. (2015). Single peptide ligand-functionalized uniform hollow mesoporous silica nanoparticles achieving dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells. International Journal of Nanomedicine, 10, 1855.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu, Y.-J., Lin, P.-Y., Huang, P.-H., Kuo, C.-Y., Shalumon, K., Chen, M.-Y., & Chen, J.-P. (2018). Magnetic graphene oxide for dual targeted delivery of doxorubicin and photothermal therapy. Nanomaterials, 8(4), 193.

    Article  PubMed Central  CAS  Google Scholar 

  • Luo, Y., Yang, H., Zhou, Y.-F., & Hu, B. (2020). Dual and multi-targeted nanoparticles for site-specific brain drug delivery. Journal of Controlled Release, 317, 195–215.

    Article  CAS  PubMed  Google Scholar 

  • Obraztsov, A., Obraztsova, E., Tyurnina, A., & Zolotukhin, A. (2007). Chemical vapor deposition of thin graphite films of nanometer thickness. Carbon, 45(10), 2017–2021.

    Article  CAS  Google Scholar 

  • Peng, Y., Zhao, Y., Chen, Y., Yang, Z., Zhang, L., **ao, W., Yang, J., Guo, L., & Wu, Y. (2018). Dual-targeting for brain-specific liposomes drug delivery system: Synthesis and preliminary evaluation. Bioorganic & Medicinal Chemistry, 26(16), 4677–4686.

    Article  CAS  Google Scholar 

  • Qin, L., Wang, C. Z., Fan, H. J., Zhang, C. J., Zhang, H. W., Lv, M. H., & Cui, S. D. (2014). A dual-targeting liposome conjugated with transferrin and arginine-glycine-aspartic acid peptide for glioma-targeting therapy. Oncology Letters, 8(5), 2000–2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren, J., Shen, S., Wang, D., **, Z., Guo, L., Pang, Z., Qian, Y., Sun, X., & Jiang, X. (2012). The targeted delivery of anticancer drugs to brain glioma by PEGylated oxidized multi-walled carbon nanotubes modified with angiopep-2. Biomaterials, 33(11), 3324–3333.

    Article  CAS  PubMed  Google Scholar 

  • Rezayan, A. H., Mousavi, M., Kheirjou, S., Amoabediny, G., Ardestani, M. S., & Mohammadnejad, J. (2016). Monodisperse magnetite (Fe3O4) nanoparticles modified with water soluble polymers for the diagnosis of breast cancer by MRI method. Journal of Magnetism and Magnetic Materials, 420, 210–217.

    Article  CAS  Google Scholar 

  • Sun, Z., Yan, X., Liu, Y., Huang, L., Kong, C., Qu, X., Wang, M., Gao, R., & Qin, H. (2017). Application of dual targeting drug delivery system for the improvement of anti-glioma efficacy of doxorubicin. Oncotarget, 8(35), 58823.

    Article  PubMed  PubMed Central  Google Scholar 

  • van der Meel, R., Vehmeijer, L. J., Kok, R. J., Storm, G., & van Gaal, E. V. (2013). Ligand-targeted particulate nanomedicines undergoing clinical evaluation: Current status. Advanced Drug Delivery Reviews, 65(10), 1284–1298.

    Article  PubMed  CAS  Google Scholar 

  • Wang, X., Lin, X., Dravid, V. P., Ketterson, J. B., & Chang, R. P. (1995). Carbon nanotubes synthesized in a hydrogen arc discharge. Applied Physics Letters, 66(18), 2430–2432.

    Article  CAS  Google Scholar 

  • Wang, S., Zhao, C., Liu, P., Wang, Z., Ding, J., & Zhou, W. (2018). Facile construction of dual-targeting delivery system by using lipid capped polymer nanoparticles for anti-glioma therapy. RSC Advances, 8(1), 444–453.

    Article  CAS  Google Scholar 

  • **n, H., Jiang, X., Gu, J., Sha, X., Chen, L., Law, K., Chen, Y., Wang, X., Jiang, Y., & Fang, X. (2011). Angiopep-conjugated poly (ethylene glycol)-co-poly (ε-caprolactone) nanoparticles as dual-targeting drug delivery system for brain glioma. Biomaterials, 32(18), 4293–4305.

    Article  CAS  PubMed  Google Scholar 

  • **ong, X.-B., UludaÄŸ, H., & Lavasanifar, A. (2010). Virus-mimetic polymeric micelles for targeted siRNA delivery. Biomaterials, 31(22), 5886–5893.

    Article  CAS  PubMed  Google Scholar 

  • Xu, Q., Liu, Y., Su, S., Li, W., Chen, C., & Wu, Y. (2012). Anti-tumor activity of paclitaxel through dual-targeting carrier of cyclic RGD and transferrin conjugated hyperbranched copolymer nanoparticles. Biomaterials, 33(5), 1627–1639.

    Article  CAS  PubMed  Google Scholar 

  • Yang, X., Chen, Y., Yuan, R., Chen, G., Blanco, E., Gao, J., & Shuai, X. (2008). Folate-encoded and Fe3O4-loaded polymeric micelles for dual targeting of cancer cells. Polymer, 49(16), 3477–3485.

    Article  CAS  Google Scholar 

  • Yang, X., Wang, Y., Huang, X., Ma, Y., Huang, Y., Yang, R., Duan, H., & Chen, Y. (2011). Multi-functionalized graphene oxide based anticancer drug-carrier with dual-targeting function and pH-sensitivity. Journal of Materials Chemistry, 21(10), 3448–3454.

    Article  CAS  Google Scholar 

  • Yuan, M., Qiu, Y., Zhang, L., Gao, H., & He, Q. (2016). Targeted delivery of transferrin and TAT co-modified liposomes encapsulating both paclitaxel and doxorubicin for melanoma. Drug Delivery, 23(4), 1171–1183.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, W., Yu, Z.-L., Wu, M., Ren, J.-G., **a, H.-F., Sa, G.-L., Zhu, J.-Y., Pang, D.-W., Zhao, Y.-F., & Chen, G. (2017). Magnetic and folate functionalization enables rapid isolation and enhanced tumor-targeting of cell-derived microvesicles. ACS Nano, 11(1), 277–290.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, Y., Cao, J., & Yuan, Z. (2020). Strategies and challenges to improve the performance of tumor-associated active targeting. Journal of Materials Chemistry B, 8(18), 3959–3971.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, Z., Zhao, Y., **e, C., Chen, C., Lin, D., Wang, S., Cui, X., Guo, Z., & Zhou, J. (2019). Dual-active targeting liposomes drug delivery system for bone metastatic breast cancer: Synthesis and biological evaluation. Chemistry and Physics of Lipids, 223, 104785.

    Article  CAS  PubMed  Google Scholar 

  • Zhu, Y., Feijen, J., & Zhong, Z. (2018). Dual-targeted nanomedicines for enhanced tumor treatment. Nano Today, 18, 65–85.

    Article  CAS  Google Scholar 

  • Zong, T., Mei, L., Gao, H., Shi, K., Chen, J., Wang, Y., Zhang, Q., Yang, Y., & He, Q. (2014). Enhanced glioma targeting and penetration by dual-targeting liposome co-modified with T7 and TAT. Journal of Pharmaceutical Sciences, 103(12), 3891–3901.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chemical Engineering Faculty, University of Tehran, Tehran, Iran

    Ghassem Amoabediny, Ghazal Rastegar, Mahin Maleki, Dina Jafari & Zeynab Amoabediny

  2. Research Center for New Technologies in Life Science Engineering (UTLSE), University of Tehran, Tehran, Iran

    Ghassem Amoabediny, Ghazal Rastegar, Mahin Maleki, Dina Jafari, Zeynab Amoabediny, Fardin Rahimi & Mina Khodarahmi

  3. College of Engineering, Department of Chemical Engineering, University of Tehran, Tehran, Iran

    Ghassem Amoabediny

  4. Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran

    Fardin Rahimi & Mina Khodarahmi

Authors
  1. Ghassem Amoabediny
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ghazal Rastegar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mahin Maleki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dina Jafari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zeynab Amoabediny
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fardin Rahimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mina Khodarahmi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ghassem Amoabediny .

Editor information

Editors and Affiliations

  1. AMR and Nanomedicine Lab Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, India

    Muthupandian Saravanan

  2. Department of Pharmaceutical Biotechnology, School of Pharmacy,, Shahid Beheshti University of Medical Science, Tehran, Iran

    Hamed Barabadi

Rights and permissions

Reprints and permissions

Copyright information

© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Amoabediny, G. et al. (2021). Dual Targeting Drug Delivery for Cancer Theranostics. In: Saravanan, M., Barabadi, H. (eds) Cancer Nanotheranostics. Nanotechnology in the Life Sciences. Springer, Cham. https://doi.org/10.1007/978-3-030-74330-7_2

Download citation

Publish with us

Policies and ethics

Search

Navigation