Medical research is at the forefront of addressing pressing global challenges, including preventing and treating cardiovascular, autoimmune, and oncological diseases, neurodegenerative disorders, and the growing resistance of pathogens to antibiotics. Understanding the molecular mechanisms underlying these diseases, using advanced medical approaches and cutting-edge technologies, structure-based drug design, and personalized medicine, is critical for developing effective therapies, specifically anticancer treatments. Background/Objectives: One of the key drivers of cancer at the cellular level is the abnormal activity of protein enzymes, specifically serine, threonine, or tyrosine residues, through a process known as phosphorylation. While tyrosine kinase-mediated phosphorylation constitutes a minor fraction of total cellular phosphorylation, its dysregulation is critically linked to carcinogenesis and tumor progression. Methods: Small-molecule inhibitors, such as imatinib or erlotinib, are designed to halt this process, restoring cellular equilibrium and offering targeted therapeutic approaches. However, challenges persist, including frequent drug resistance and severe side effects associated with these therapies. Nanomedicine offers a transformative potential to overcome these limitations. Results: By leveraging the unique properties of nanomaterials, it is possible to achieve precise drug delivery, enhance accumulation at target sites, and improve therapeutic efficacy. Examples include nanoparticle-based delivery systems for TKIs and the combination of nanomaterials with photothermal or photodynamic therapies to enhance treatment effectiveness. Combining nanomedicine with traditional treatments holds promise and perspective for synergistic and more effective cancer management. Conclusions: This review delves into recent advances in understanding tyrosine kinase activity, the mechanisms of their inhibition, and the innovative integration of nanomedicine to revolutionize cancer treatment strategies.
- Klíčová slova
- anticancer treatment, drug delivery, gold nanoparticles, metal nanoparticles, nanomaterials, nanomedicine, tyrosine kinase inhibitors,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: The present study reports on examination of the effects of encapsulating the tyrosine kinase inhibitors (TKIs) vandetanib and lenvatinib into a biomacromolecular ferritin-based delivery system. METHODS: The encapsulation of TKIs was performed via two strategies: i) using an active reversible pH-dependent reassembly of ferritin´s quaternary structure and ii) passive loading of hydrophobic TKIs through the hydrophobic channels at the junctions of ferritin subunits. After encapsulation, ferritins were surface-functionalized with folic acid promoting active-targeting capabilities. RESULTS: The physico-chemical and nanomechanical analyses revealed that despite the comparable encapsulation efficiencies of both protocols, the active loading affects stability and rigidity of ferritins, plausibly due to their imperfect reassembly. Biological experiments with hormone-responsive breast cancer cells (T47-D and MCF-7) confirmed the cytotoxicity of encapsulated and folate-targeted TKIs to folate-receptor positive cancer cells, but only limited cytotoxic effects to healthy breast epithelium. Importantly, the long-term cytotoxic experiments revealed that compared to the pH-dependent encapsulation, the passively-loaded TKIs exert markedly higher anticancer activity, most likely due to undesired influence of harsh acidic environment used for the pH-dependent encapsulation on the TKIs' structural and functional properties. CONCLUSION: Since the passive loading does not require a reassembly step for which acids are needed, the presented investigation serves as a solid basis for future studies focused on encapsulation of small hydrophobic molecules.
- Klíčová slova
- drug delivery, lenvatinib, nanomedicine, vandetanib,
- MeSH
- biokompatibilní materiály chemie MeSH
- buněčná smrt účinky léků MeSH
- buněčné klony MeSH
- buněčné linie MeSH
- chinazoliny chemie farmakologie MeSH
- chinoliny chemie farmakologie MeSH
- difuze MeSH
- fenylmočovinové sloučeniny chemie farmakologie MeSH
- ferritiny chemie MeSH
- inhibitory proteinkinas farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- koně MeSH
- kyselina listová chemie MeSH
- lékové transportní systémy * MeSH
- lidé MeSH
- nosiče léků chemie MeSH
- piperidiny chemie farmakologie MeSH
- pohyb buněk účinky léků MeSH
- povrchové vlastnosti MeSH
- protinádorové látky farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biokompatibilní materiály MeSH
- chinazoliny MeSH
- chinoliny MeSH
- fenylmočovinové sloučeniny MeSH
- ferritiny MeSH
- inhibitory proteinkinas MeSH
- kyselina listová MeSH
- lenvatinib MeSH Prohlížeč
- nosiče léků MeSH
- piperidiny MeSH
- protinádorové látky MeSH
- vandetanib MeSH Prohlížeč
