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@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.
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