title: Site-Directed Conjugation of Antibodies to Apoferritin Nanocarrier for Targeted Drug Delivery to Prostate Cancer Cells.
abstract: Herein, we describe a novel approach for targeting of ubiquitous protein apoferritin (APO)-encapsulating doxorubicin (DOX) to prostate cancer using antibodies against prostate-specific membrane antigen (PSMA). The conjugation of anti-PSMA antibodies and APO was carried out using HWRGWVC heptapeptide, providing their site-directed orientation. The prostate-cancer-targeted and nontargeted nanocarriers were tested using LNCaP and HUVEC cell lines. A total of 90% of LNCaP cells died after treatment with DOX (0.25 μM) or DOX in nontargeted and prostate-cancer-targeted APO, proving that the encapsulated DOX toxicity for LNCaP cells remained the same. Free DOX showed higher toxicity for nonmalignant cells, whereas the toxicity was lower after treatment with the same dosage of APO-encapsulated DOX (APODOX) and even more in prostate-cancer-targeted APODOX. Hemolytic assay revealed exceptional hemocompatibility of the entire nanocarrier. The APO encapsulation mechanism ensures applicability using a wide variety of chemotherapeutic drugs, and the presented surface modification enables targeting to various tumors.
authors.affiliation: 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.
authors.forename: Simona
authors.initials: S
authors.lastname: Dostalova
authors.affiliation: Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University in Prague and University Hospital Motol , V Uvalu 84/1, Prague 5 CZ-150 06, Czech Republic.|Department of Biochemistry, Faculty of Science, Charles University in Prague , Hlavova 2030/8, Prague 2 CZ-128 43, Czech Republic.
authors.forename: Tereza
authors.initials: T
authors.lastname: Cerna
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Hynek
authors.affiliation: 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.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Koudelkova
authors.affiliation: Department of Chemistry, Faculty of Science, Masaryk University , Kotlarska 2, Brno CZ-611 37, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Vaculovic
authors.affiliation: 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.
authors.forename: Pavel
authors.initials: P
authors.lastname: Kopel
authors.affiliation: Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University in Prague and University Hospital Motol , V Uvalu 84/1, Prague 5 CZ-150 06, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Hrabeta
authors.affiliation: 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.
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Heger
authors.affiliation: 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.
authors.forename: Marketa
authors.initials: M
authors.lastname: Vaculovicova
authors.affiliation: Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University in Prague and University Hospital Motol , V Uvalu 84/1, Prague 5 CZ-150 06, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Eckschlager
authors.affiliation: Department of Biochemistry, Faculty of Science, Charles University in Prague , Hlavova 2030/8, Prague 2 CZ-128 43, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Stiborova
authors.affiliation: 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.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Adam
mesh_terms: D000906:Antibodies / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001052:Apoferritins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D004317:Doxorubicin; D001052:Apoferritins
keywords: antibodies; apoferritin; doxorubicin; nanomedicine; targeted drug delivery