Ferritin, a naturally occurring iron storage protein, has gained significant attention as a drug delivery platform due to its inherent biocompatibility and capacity to encapsulate therapeutic agents. In this study, we successfully genetically engineered human H ferritin by incorporating 4 or 6 tryptophan residues per subunit, strategically oriented towards the inner cavity of the nanoparticle. This modification aimed to enhance the encapsulation of hydrophobic drugs into the ferritin cage. Comprehensive characterization of the mutants revealed that only the variant carrying four tryptophan substitutions per subunit retained the ability to disassemble and reassemble properly. As a proof of concept, we evaluated the loading capacity of this mutant with ellipticine, a natural hydrophobic indole alkaloid with multimodal anticancer activity. Our data demonstrated that this specific mutant exhibited significantly higher efficiency in loading ellipticine compared to human H ferritin. Furthermore, to evaluate the versatility of this hydrophobicity-enhanced ferritin nanoparticle as a drug carrier, we conducted a comparative study by also encapsulating doxorubicin, a commonly used anticancer drug. Subsequently, we tested both ellipticine and doxorubicin-loaded nanoparticles on a promyelocytic leukemia cell line, demonstrating efficient uptake by these cells and resulting in the expected cytotoxic effect.

• Keywords
• doxorubicin, drug delivery, ellipticine, ferritin, hydrophobic drugs, nanoparticle, protein engineering, tumor cells,
• MeSH
• Apoferritins genetics   MeSH
• Doxorubicin pharmacology   chemistry   MeSH
• Ellipticines * MeSH
• Ferritins genetics   chemistry   MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Drug Delivery Systems MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Nanoparticles * chemistry   MeSH
• Drug Carriers chemistry   MeSH
• Antineoplastic Agents * pharmacology   chemistry   MeSH
• Tryptophan MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Apoferritins MeSH
• Doxorubicin MeSH
• Ellipticines * MeSH
• Ferritins MeSH
• Drug Carriers MeSH
• Antineoplastic Agents * MeSH
• Tryptophan MeSH

A tyrosine kinase inhibitor, vandetanib (Van), is an anticancer drug affecting the signaling of VEGFR, EGFR and RET protooncogenes. Van is primarily used for the treatment of advanced or metastatic medullary thyroid cancer; however, its usage is significantly limited by side effects, particularly cardiotoxicity. One approach to minimize them is the encapsulation or binding of Van in- or onto a suitable carrier, allowing targeted delivery to tumor tissue. Herein, we constructed a nanocarrier based on apoferritin associated with Van (ApoVan). Based on the characteristics obtained by analyzing the average size, the surface ζ-potential and the polydispersive index, ApoVan nanoparticles exhibit long-term stability and maintain their morphology. Experiments have shown that ApoVan complex is relatively stable during storage. It was found that Van is gradually released from its ApoVan form into the neutral environment (pH 7.4) as well as into the acidic environment (pH 6.5). The effect of free Van and ApoVan on neuroblastoma and medullary thyroid carcinoma cell lines revealed that both forms were toxic in both used cell lines, and minimal differences between ApoVan and Van were observed. Thus, we assume that Van might not be encapsulated into the cavity of apoferritin, but instead only binds to its surface.

• Keywords
• apoferritin, cancer targeting, medullary thyroid cancer, neuroblastoma, vandetanib,
• MeSH
• Apoferritins chemistry   pharmacokinetics   MeSH
• Quinazolines chemistry   pharmacokinetics   MeSH
• Hydrogen-Ion Concentration MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Nanoparticles chemistry   MeSH
• Piperidines chemistry   pharmacokinetics   MeSH
• Drug Stability MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Apoferritins MeSH
• Quinazolines MeSH
• Piperidines MeSH
• vandetanib MeSH Browser

The increasing number of scientific publications focusing on magnetic materials indicates growing interest in the broader scientific community. Substantial progress was made in the synthesis of magnetic materials of desired size, morphology, chemical composition, and surface chemistry. Physical and chemical stability of magnetic materials is acquired by the coating. Moreover, surface layers of polymers, silica, biomolecules, etc. can be designed to obtain affinity to target molecules. The combination of the ability to respond to the external magnetic field and the rich possibilities of coatings makes magnetic materials universal tool for magnetic separations of small molecules, biomolecules and cells. In the biomedical field, magnetic particles and magnetic composites are utilized as the drug carriers, as contrast agents for magnetic resonance imaging (MRI), and in magnetic hyperthermia. However, the multifunctional magnetic particles enabling the diagnosis and therapy at the same time are emerging. The presented review article summarizes the findings regarding the design and synthesis of magnetic materials focused on biomedical applications. We highlight the utilization of magnetic materials in separation/preconcentration of various molecules and cells, and their use in diagnosis and therapy.

• Keywords
• magnetic resonance imaging, nanocarrier, nanoscale, preconcentration, separation, silica, theranostics, therapeutic agents,
• Publication type
• Journal Article MeSH
• Review MeSH

Due to many adverse effects of conventional chemotherapy, novel methods of targeting drugs to cancer cells are being investigated. Nanosize carriers are a suitable platform for this specific delivery. Herein, we evaluated the long-term stability of the naturally found protein nanocarrier apoferritin (Apo) with encapsulated doxorubicin (Dox). The encapsulation was performed using Apo's ability to disassemble reversibly into its subunits at low pH (2.7) and reassemble in neutral pH (7.2), physically entrapping drug molecules in its cavity (creating ApoDox). In this study, ApoDox was prepared in water and phosphate-buffered saline and stored for 12 weeks in various conditions (-20°C, 4°C, 20°C, and 37°C in dark, and 4°C and 20°C under ambient light). During storage, a very low amount of prematurely released drug molecules were detected (maximum of 7.5% for ApoDox prepared in PBS and 4.4% for ApoDox prepared in water). Fourier-transform infrared spectra revealed no significant differences in any of the samples after storage. Most of the ApoDox prepared in phosphate-buffered saline and ApoDox prepared in water and stored at -20°C formed very large aggregates (up to 487% of original size). Only ApoDox prepared in water and stored at 4°C showed no significant increase in size or shape. Although this storage caused slower internalization to LNCaP prostate cancer cells, ApoDox (2.5 μM of Dox) still retained its ability to inhibit completely the growth of 1.5×104 LNCaP cells after 72 hours. ApoDox stored at 20°C and 37°C in water was not able to deliver Dox inside the nucleus, and thus did not inhibit the growth of the LNCaP cells. Overall, our study demonstrates that ApoDox has very good stability over the course of 12 weeks when stored properly (at 4°C), and is thus suitable for use as a nanocarrier in the specific delivery of anticancer drugs to patients.

• Keywords
• anticancer therapy, doxorubicin-loaded apoferritin, encapsulation, long-term stability, protein nanocarriers,
• MeSH
• Apoferritins administration & dosage   chemistry   pharmacokinetics   MeSH
• Doxorubicin administration & dosage   chemistry   MeSH
• Hydrogen-Ion Concentration MeSH
• Drug Delivery Systems MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Prostatic Neoplasms drug therapy   pathology   MeSH
• Drug Carriers administration & dosage   chemistry   pharmacokinetics   MeSH
• Antineoplastic Agents administration & dosage   pharmacokinetics   pharmacology   MeSH
• Drug Screening Assays, Antitumor MeSH
• Drug Stability MeSH
• Drug Liberation MeSH
• Water chemistry   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Apoferritins MeSH
• Doxorubicin MeSH
• Drug Carriers MeSH
• Antineoplastic Agents MeSH
• Water MeSH

Liposome-based drug delivery systems hold great potential for cancer therapy. The aim of this study was to design a nanodevice for targeted anchoring of liposomes (with and without cholesterol) with encapsulated anticancer drugs and antisense N-myc gene oligonucleotide attached to its surface. To meet this main aim, liposomes with encapsulated doxorubicin, ellipticine and etoposide were prepared. They were further characterized by measuring their fluorescence intensity, whereas the encapsulation efficiency was estimated to be 16%. The hybridization process of individual oligonucleotides forming the nanoconstruct was investigated spectrophotometrically and electrochemically. The concentrations of ellipticine, doxorubicin and etoposide attached to the nanoconstruct in gold nanoparticle-modified liposomes were found to be 14, 5 and 2 µg·mL(-1), respectively. The study succeeded in demonstrating that liposomes are suitable for the transport of anticancer drugs and the antisense oligonucleotide, which can block the expression of the N-myc gene.

• Keywords
• N-myc, doxorubicin, ellipticine, etoposide, gold nanoparticles, liposome,
• MeSH
• DNA, Antisense chemistry   therapeutic use   MeSH
• Doxorubicin chemistry   therapeutic use   MeSH
• Ellipticines chemistry   therapeutic use   MeSH
• Etoposide chemistry   therapeutic use   MeSH
• Fluorescence MeSH
• Drug Delivery Systems * MeSH
• Humans MeSH
• Liposomes chemistry   therapeutic use   MeSH
• Magnetite Nanoparticles chemistry   therapeutic use   MeSH
• Neoplasms drug therapy   MeSH
• N-Myc Proto-Oncogene Protein antagonists & inhibitors   genetics   MeSH
• Gold chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• DNA, Antisense MeSH
• Doxorubicin MeSH
• Ellipticines MeSH
• Etoposide MeSH
• Liposomes MeSH
• Magnetite Nanoparticles MeSH
• N-Myc Proto-Oncogene Protein MeSH
• Gold MeSH

Cisplatin belongs to the most widely used cytostatic drugs. The determination of the presence of the DNA-cisplatin adducts may not only signal the guanine-rich regions but also monitor the interaction reaction between DNA and the drug in terms of speed of interaction. In this work, the combined advantages of magnetic particles-based isolation/purification with fluorescent properties of quantum dots (QDs) and antibodies targeted on specific recognition of DNA-cisplatin adducts are demonstrated. The formation of a complex between magnetic particles with surface modified by anti-dsDNA antibody, cisplatin-modified DNA and QDs labelled anti-cisplatin-modified DNA antibody was suggested and optimized.

• Keywords
• Anti-DNA Antibodies, Cisplatin, Magnetic Separation, Sandwich Analysis,
• Publication type
• Journal Article MeSH