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

J 2018

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

DOSTALOVA, Simona, Hana POLANSKÁ, Markéta SVOBODOVÁ, Jan BALVAN, Olga KRYSTOFOVA et. al.

Basic information

Original name

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

Authors

DOSTALOVA, Simona (203 Czech Republic), Hana POLANSKÁ (203 Czech Republic, belonging to the institution), Markéta SVOBODOVÁ (203 Czech Republic, belonging to the institution), Jan BALVAN (203 Czech Republic, belonging to the institution), Olga KRYSTOFOVA (203 Czech Republic), Yazan HADDAD (203 Czech Republic), Sona KRIZKOVA (203 Czech Republic), Michal MASAŘÍK (203 Czech Republic, belonging to the institution), Tomas ECKSCHLAGER (203 Czech Republic), Marie STIBOROVA (203 Czech Republic), Zbynek HEGER (203 Czech Republic) and Vojtech ADAM (203 Czech Republic, guarantor)

Edition

Scientific reports, LONDON, NATURE PUBLISHING GROUP, 2018, 2045-2322

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30105 Physiology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 4.011

RIV identification code

RIV/00216224:14110/18:00104162

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1038/s41598-018-26772-z

UT WoS

000434777700013

Keywords in English

doxorubicin ; apoferritin

Abstract

V originále

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.

Citovat

DOSTALOVA, Simona, Hana POLANSKÁ, Markéta SVOBODOVÁ, Jan BALVAN, Olga KRYSTOFOVA, Yazan HADDAD, Sona KRIZKOVA, Michal MASAŘÍK, Tomas ECKSCHLAGER, Marie STIBOROVA, Zbynek HEGER and Vojtech ADAM. Prostate-Specific Membrane Antigen-Targeted Site-Directed Antibody-Conjugated Apoferritin Nanovehicle Favorably Influences In Vivo Side Effects of Doxorubicin. Scientific reports. LONDON: NATURE PUBLISHING GROUP, 2018, vol. 8, No 8867, p. 1-13. ISSN 2045-2322. Available from: https://dx.doi.org/10.1038/s41598-018-26772-z.

@article{1454356,
   author = {Dostalova, Simona and Polanská, Hana and Svobodová, Markéta and Balvan, Jan and Krystofova, Olga and Haddad, Yazan and Krizkova, Sona and Masařík, Michal and Eckschlager, Tomas and Stiborova, Marie and Heger, Zbynek and Adam, Vojtech},
   article_location = {LONDON},
   article_number = {8867},
   doi = {http://dx.doi.org/10.1038/s41598-018-26772-z},
   keywords = {doxorubicin ; apoferritin},
   language = {eng},
   issn = {2045-2322},
   journal = {Scientific reports},
   title = {Prostate-Specific Membrane Antigen-Targeted Site-Directed Antibody-Conjugated Apoferritin Nanovehicle Favorably Influences In Vivo Side Effects of Doxorubicin},
   volume = {8},
   year = {2018}
}

TY  - JOUR
ID  - 1454356
AU  - Dostalova, Simona - Polanská, Hana - Svobodová, Markéta - Balvan, Jan - Krystofova, Olga - Haddad, Yazan - Krizkova, Sona - Masařík, Michal - Eckschlager, Tomas - Stiborova, Marie - Heger, Zbynek - Adam, Vojtech
PY  - 2018
TI  - Prostate-Specific Membrane Antigen-Targeted Site-Directed Antibody-Conjugated Apoferritin Nanovehicle Favorably Influences In Vivo Side Effects of Doxorubicin
JF  - Scientific reports
VL  - 8
IS  - 8867
SP  - 1-13
EP  - 1-13
PB  - NATURE PUBLISHING GROUP
SN  - 20452322
KW  - doxorubicin
KW  - apoferritin
N2  - 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.
ER  -

DOSTALOVA, Simona, Hana POLANSKÁ, Markéta SVOBODOVÁ, Jan BALVAN, Olga KRYSTOFOVA, Yazan HADDAD, Sona KRIZKOVA, Michal MASAŘÍK, Tomas ECKSCHLAGER, Marie STIBOROVA, Zbynek HEGER and Vojtech ADAM. Prostate-Specific Membrane Antigen-Targeted Site-Directed Antibody-Conjugated Apoferritin Nanovehicle Favorably Influences In Vivo Side Effects of Doxorubicin. \textit{Scientific reports}. LONDON: NATURE PUBLISHING GROUP, 2018, vol.~8, No~8867, p.~1-13. ISSN~2045-2322. Available from: https://dx.doi.org/10.1038/s41598-018-26772-z.

Detailed Information on Publication Record