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.
- MeSH
- antigeny povrchové imunologie MeSH
- apoferritiny škodlivé účinky terapeutické užití MeSH
- doxorubicin škodlivé účinky analogy a deriváty terapeutické užití MeSH
- glutamátkarboxypeptidasa II imunologie MeSH
- heterografty MeSH
- imunokonjugáty terapeutické užití MeSH
- játra účinky léků MeSH
- ledviny účinky léků MeSH
- lidé MeSH
- myši inbrední BALB C MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory prostaty farmakoterapie terapie MeSH
- nanokonjugáty terapeutické užití MeSH
- srdce účinky léků MeSH
- výsledek terapie MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny povrchové MeSH
- apoferritin doxorubicin MeSH Prohlížeč
- apoferritiny MeSH
- doxorubicin MeSH
- FOLH1 protein, human MeSH Prohlížeč
- glutamátkarboxypeptidasa II MeSH
- imunokonjugáty MeSH
- nanokonjugáty MeSH
Nanomedicine as a continuously evolving discipline is still looking for a structure with perfect properties that is usable as a multifunctional transporter. Great potential is attributed to synthetic materials such as fullerenes, porous hollow silica nanoparticles and single-wall nanotubes, among others. However, materials that are natural to the human body are more acceptable by the organism, and thus become an attractive approach in this field of research. Ferritins are proteins that naturally occur in most living organisms throughout evolution and may be a possible transporter choice. Numerous applications have demonstrated the possibilities of iron-free ferritins, called apoferritins, serving as platforms for various nanomedical purposes This article summarizes the advantages and disadvantages of these proteins and discusses their practical applications and future perspectives.
- Klíčová slova
- horse spleen ferritin, magnetic resonance imaging, nanoscale, nanotrasporter, photodynamic therapy, self-assembly, therapeutic agents,
- MeSH
- apoferritiny chemie terapeutické užití MeSH
- biosenzitivní techniky MeSH
- genetická terapie MeSH
- konformace proteinů MeSH
- lidé MeSH
- nanomedicína * MeSH
- nosiče léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- apoferritiny MeSH
- nosiče léků MeSH