Publication detail

Prostate-Specific Membrane Antigen-Targeted Site-Directed Antibody-Conjugated Apoferritin Nanovehicle Favorably Influences In Vivo Side Effects of Doxorubicin

DOSTÁLOVÁ, S. POLANSKÁ, H. SVOBODOVÁ, M. BALVAN, J. KRYŠTOFOVÁ, O. HADDAD, Y. KŘÍŽKOVÁ, S. MASAŘÍK, M. ECKSCHLAGER, T. STIBOROVÁ, M. HEGER, Z. ADAM, V.

Original Title

Prostate-Specific Membrane Antigen-Targeted Site-Directed Antibody-Conjugated Apoferritin Nanovehicle Favorably Influences In Vivo Side Effects of Doxorubicin

Type

journal article in Web of Science

Language

English

Original Abstract

Herein, we describe the in vivo effects of doxorubicin (DOX) encapsulated in ubiquitous protein apoferritin (APO) and its efficiency and safety in anti-tumor treatment. APODOX is both passively (through Enhanced Permeability and Retention effect) and actively targeted to tumors through prostate-specific membrane antigen (PSMA) via mouse antibodies conjugated to the surface of horse spleen APO. To achieve site-directed conjugation of the antibodies, a HWRGWVC heptapeptide linker was used. The prostate cancer-targeted and non-targeted nanocarriers were tested using subcutaneously implanted LNCaP cells in athymic mice models, and compared to free DOX. Prostate cancer-targeted APODOX retained the high potency of DOX in attenuation of tumors (with 55% decrease in tumor volume after 3 weeks of treatment). DOX and non-targeted APODOX treatment caused damage to liver, kidney and heart tissues. In contrast, no elevation in liver or kidney enzymes and negligible changes were revealed by histological assessment in prostate cancer-targeted APODOX-treated mice. Overall, we show that the APO nanocarrier provides an easy encapsulation protocol, reliable targeting, high therapeutic efficiency and very low off-target toxicity, and is thus a promising delivery system for translation into clinical use.

Keywords

In vivo effects; Doxorubicin; Apoferritin; Prostate-specific membrane; Anti-tumor treatment

Authors

DOSTÁLOVÁ, S.; POLANSKÁ, H.; SVOBODOVÁ, M.; BALVAN, J.; KRYŠTOFOVÁ, O.; HADDAD, Y.; KŘÍŽKOVÁ, S.; MASAŘÍK, M.; ECKSCHLAGER, T.; STIBOROVÁ, M.; HEGER, Z.; ADAM, V.

Released

11. 6. 2018

Publisher

Springer Nature

ISBN

2045-2322

Periodical

Scientific Reports

Year of study

8

Number

8867

State

United Kingdom of Great Britain and Northern Ireland

Pages from

1

Pages to

13

Pages count

13

URL

http://link.springer.com/article/10.1038/s41598-018-26772-z

Full text in the Digital Library

http://hdl.handle.net/11012/83822

BibTex

@article{BUT148531,
  author="Simona {Dostálová} and Hana {Polanská} and Markéta {Svobodová} and Jan {Balvan} and Olga {Kryštofová} and Yazan Abdulmajeed Eyadh {Haddad} and Soňa {Křížková} and Michal {Masařík} and Tomáš {Eckschlager} and Marie {Stiborová} and Zbyněk {Heger} and Vojtěch {Adam}",
  title="Prostate-Specific Membrane Antigen-Targeted Site-Directed Antibody-Conjugated Apoferritin Nanovehicle Favorably Influences In Vivo Side Effects of Doxorubicin",
  journal="Scientific Reports",
  year="2018",
  volume="8",
  number="8867",
  pages="1--13",
  doi="10.1038/s41598-018-26772-z",
  issn="2045-2322",
  url="http://link.springer.com/article/10.1038/s41598-018-26772-z"
}