Nanoparticle-Modified Apoferritin Nanotransfer for Targeted Cytostatic Transport

BACKGROUND: Ferritin is a globular intracellular protein that acts as the main reservoir for iron. Malignancies are associated with increased plasma ferritin concentrations. A number of studies show that tumor cells express high levels of transferrin receptors (TfR). Increased TfR expression was observed in prostate carcinoma. Apoferritin (APO) can be used as a protein nanotransporter into which a suitable medicinal substance can be encapsulated. Nanoparticles increase the permeability of tumor cells to nanotransporters and have a photothermal effect. The aim of this study was to encapsulate doxorubicin (DOX) into APO and to modify the resulting APO/DOX with gold (AuNPs) and silver nanoparticles prepared by green synthesis (AgNPsGS).

METHODS: APO was characterized using 10% sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE) - 120 V, 60 min, 24 mM Tris, 0.2 M glycine, 3 mM SDS. DOX fluorescence (Ex 480 nm; Em 650 nm) was observed, with a typical absorption maximum at 560 nm. Electrochemical measurement was performed in Brdicka solution (three-electrode setup). AgNPsGS were prepared by green synthesis using clover (Trifolium pratense L.).

RESULTS: An electrophoretic study of APO and APO/DOX (5-100 μg/mL) was performed and the behavior of APO and APO/DOX (10 μM) as a function of pH was monitored. In an acidic environment, APO forms subunits of about 20 kDa; in an alkaline medium, it forms a globular protein of about 450 kDa. A change in APO/DOX mobility (about by 10%) was observed. A film of gold nanoparticles was applied to the APO/DOX surface. APO/DOX-AuNPs were washed with ultra-pure water. pH-dependent release of DOX a was monitored. The amount of DOX analyzed was increased by up to 50%. Furthermore, an AgNPsGS-DOX complex (1 mg AgNPsGS/100 μM DOX) was generated and prepared. Subsequently, the AgNPsGS-DOX complex was encapsulated into APO. To further improve therapeutic efficacy, the APO/AgNPsGS-DOX complex was coated with an Au layer. APO/AgNPsGS-DOX/AuNPs were stable and DOX was released from the complex after physical parameters had changed.

CONCLUSION: APO nanocomplexes were prepared and modified to increase therapeutic efficacy against tumors. Tumor cell targeting was achieved by binding to TfR and via increased tumor cell permeability and retention. Release of the drug was made possible due to a pH change and photothermal activation that will now be tested. This work was supported by COST European Cholangiocarcinoma Network CA18122 and International Collaboration Project of The European Technology Platform for Nanomedicine. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 21. 3. 2019 Accepted: 14. 5. 2019.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:32

Enthalten in:

Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti - 32(2019), 3 vom: 20., Seite 197-200

Sprache:

Englisch

Weiterer Titel:

Nanočásticemi modifikovaný apoferritinový nanotransportér pro cílený transport cytostatik

Beteiligte Personen:

Čížek, M [VerfasserIn]
Gargulák, M [VerfasserIn]
Sehnal, K [VerfasserIn]
Uhlířová, D [VerfasserIn]
Staňková, M [VerfasserIn]
Dočekalová, M [VerfasserIn]
Ruttkay-Nedecký, B [VerfasserIn]
Zídková, J [VerfasserIn]
Kizek, R [VerfasserIn]

Links:

Volltext

Themen:

3M4G523W1G
7440-57-5
80168379AG
9013-31-4
Antibiotics, Antineoplastic
Apoferritin doxorubicin
Apoferritin nanotransporter
Apoferritins
Doxorubicin
Gold
Gold nanoparticles
Journal Article
Malignant tumors
Nanomedicine
Prostate tumors
Receptors, Transferrin
Silver
Silver nanoparticles
Targeted therapy
Transferin receptors

Anmerkungen:

Date Completed 06.12.2019

Date Revised 17.12.2019

published: Print

Citation Status MEDLINE

doi:

10.14735/amko2019197

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM298330415