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

S. Dostalova, H. Polanska, M. Svobodova, J. Balvan, O. Krystofova, Y. Haddad, S. Krizkova, M. Masarik, T. Eckschlager, M. Stiborova, Z. Heger, V. Adam,

. 2018 ; 8 (1) : 8867. [pub] 20180611

Jazyk angličtina Země Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19045417

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.

Citace poskytuje Crossref.org

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$a Dostalova, Simona $u Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno, CZ-613 00, Czech Republic. Central European Institute of Technology, Brno University of Technology, Purkynova 123, Brno, CZ-612 00, Czech Republic.
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$a 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.
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$a Polanska, Hana $u Department of Pathological Physiology and Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 753/5, Brno, CZ-625 00, Czech Republic.
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$a Svobodova, Marketa $u Department of Pathological Physiology and Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 753/5, Brno, CZ-625 00, Czech Republic.
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$a Balvan, Jan $u Department of Pathological Physiology and Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 753/5, Brno, CZ-625 00, Czech Republic. TESCAN ORSAY HOLDING a.s., Libusina trida 863/21, Brno, CZ-623 00, Czech Republic.
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$a Krystofova, Olga $u Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno, CZ-613 00, Czech Republic. Central European Institute of Technology, Brno University of Technology, Purkynova 123, Brno, CZ-612 00, Czech Republic.
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$a Haddad, Yazan $u Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno, CZ-613 00, Czech Republic. Central European Institute of Technology, Brno University of Technology, Purkynova 123, Brno, CZ-612 00, Czech Republic.
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$a Krizkova, Sona $u Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno, CZ-613 00, Czech Republic. Central European Institute of Technology, Brno University of Technology, Purkynova 123, Brno, CZ-612 00, Czech Republic.
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$a Masarik, Michal $u Department of Pathological Physiology and Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 753/5, Brno, CZ-625 00, Czech Republic.
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$a Eckschlager, Tomas $u Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, V Uvalu 84/1, Prague 5, CZ-150 06, Czech Republic.
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$a Stiborova, Marie $u Department of Biochemistry, Faculty of Science, Charles University, Hlavova 2030/8, Prague 2, CZ-128 43, Czech Republic.
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$a Heger, Zbynek $u Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno, CZ-613 00, Czech Republic. Central European Institute of Technology, Brno University of Technology, Purkynova 123, Brno, CZ-612 00, Czech Republic.
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$a Adam, Vojtech $u Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno, CZ-613 00, Czech Republic. vojtech.adam@mendelu.cz. Central European Institute of Technology, Brno University of Technology, Purkynova 123, Brno, CZ-612 00, Czech Republic. vojtech.adam@mendelu.cz.
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