Modulation of Induced Cytotoxicity of Doxorubicin by Using Apoferritin and Liposomal Cages

International Journal of Molecular Sciences

Jaromir Gumulec²  Michaela Fojtu²  Martina Raudenska²  Marketa Sztalmachova²  Anna Skotakova²  Jana Vlachova¹  Sylvie Skalickova¹  Lukas Nejdl¹  Pavel Kopel¹  Lucia Knopfova⁵  Vojtech Adam¹  Rene Kizek¹  Marie Stiborova³  Petr Babula⁴  Michal Masarik² 

[1] Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-61600 Brno, Czech Republic; E-Mails:;Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-62500 Brno, Czech Republic; E-Mails:;Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, CZ-12840 Prague 2, Czech Republic; E-Mail:;Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-62500 Brno, Czech Republic; E-Mail:;Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, CZ-62500 Brno, Czech Republic; E-Mail:

关键词: doxorubicin;    liposome;    apoferritin;    cancer;    cardiotoxicity;    modification;    encapsulation;   

DOI  :  10.3390/ijms151222960

来源: mdpi

【 摘 要 】

Doxorubicin is an effective chemotherapeutic drug, however, its toxicity is a significant limitation in therapy. Encapsulation of doxorubicin inside liposomes or ferritin cages decreases cardiotoxicity while maintaining anticancer potency. We synthesized novel apoferritin- and liposome-encapsulated forms of doxorubicin (“Apodox” and “lip-8-dox”) and compared its toxicity with doxorubicin and Myocet on prostate cell lines. Three different prostatic cell lines PNT1A, 22Rv1, and LNCaP were chosen. The toxicity of the modified doxorubicin forms was compared to conventional doxorubicin using the MTT assay, real-time cell impedance-based cell growth method (RTCA), and flow cytometry. The efficiency of doxorubicin entrapment was 56% in apoferritin cages and 42% in the liposome carrier. The accuracy of the RTCA system was verified by flow-cytometric analysis of cell viability. The doxorubicin half maximal inhibition concentrations (IC₅₀) were determined as 170.5, 234.0, and 169.0 nM for PNT1A, 22Rv1, and LNCaP, respectively by RTCA. Lip8-dox is less toxic on the non-tumor cell line PNT1A compared to doxorubicin, while still maintaining the toxicity to tumorous cell lines similar to doxorubicin or epirubicin (IC₅₀ = 2076.7 nM for PNT1A vs. 935.3 and 729.0 nM for 22Rv1 and LNCaP). Apodox IC₅₀ was determined as follows: 603.1, 1344.2, and 931.2 nM for PNT1A, 22Rv1, and LNCaP.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.