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.

Základní údaje

Originální název

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

Autoři

DOSTALOVA, Simona; Hana POLANSKÁ; Markéta SVOBODOVÁ; Jan BALVAN; Olga KRYSTOFOVA; Yazan HADDAD; Sona KRIZKOVA; Michal MASAŘÍK; Tomas ECKSCHLAGER; Marie STIBOROVA; Zbynek HEGER a Vojtech ADAM

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30105 Physiology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 4.011

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/18:00104162

Organizační jednotka

Lékařská fakulta

EID Scopus

Klíčová slova anglicky

doxorubicin ; apoferritin

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 10. 2. 2019 18:16, Soňa Böhmová

Anotace

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.