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ACS Appl Mater Interfaces. 2016 Jun 15;8(23):14430-41. doi: 10.1021/acsami.6b04286. Epub 2016 Jun 2.

Site-Directed Conjugation of Antibodies to Apoferritin Nanocarrier for Targeted Drug Delivery to Prostate Cancer Cells.

Author information

1
Department of Chemistry and Biochemistry, Mendel University in Brno , Zemedelska 1, Brno CZ-613 00, Czech Republic.
2
Central European Institute of Technology, Brno University of Technology , Purkynova 123, Brno CZ-612 00, Czech Republic.
3
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.
4
Department of Biochemistry, Faculty of Science, Charles University in Prague , Hlavova 2030/8, Prague 2 CZ-128 43, Czech Republic.
5
Department of Chemistry, Faculty of Science, Masaryk University , Kotlarska 2, Brno CZ-611 37, Czech Republic.

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.

KEYWORDS:

antibodies; apoferritin; doxorubicin; nanomedicine; targeted drug delivery

PMID:
27219717
DOI:
10.1021/acsami.6b04286
[Indexed for MEDLINE]

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