Anticancer medicines (doxorubicin and methotrexate) conjugated with magnetic nanoparticles for targeting drug delivery through iron

• Published in: Preparative biochemistry & biotechnology Vol. 43; no. 8; pp. 781 - 797
• Main Authors: Samra, Zahoor Qadir, Ahmad, Snober, Javeid, Mehwish, Dar, Nadia, Aslam, Muhammad Shahbaz, Gull, Iram, Ahmad, Mubashar Mustaneer
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Group 17.11.2013; Taylor & Francis Ltd
• Subjects: Antibodies - chemistry; antibody; anticancer; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Biochemistry; Biotechnology; Cancer; Cell Survival - drug effects; Cells; Cross-Linking Reagents - chemistry; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug Carriers - chemistry; drug delivery; FTIR; Glutaral - chemistry; HeLa Cells; Humans; Hydrogen-Ion Concentration; Immunohistochemistry; Iron - metabolism; Magnetite Nanoparticles - chemistry; Methotrexate - chemistry; Methotrexate - pharmacology; Nanoparticles; Organ Specificity; Particle Size; Spectroscopy, Fourier Transform Infrared
• ISSN: 1532-2297; 1082-6068; 1532-2297
• DOI: 10.1080/10826068.2013.782042

The uptake of iron is increased by cancer cells. Iron magnetic nanoparticles (MNP) can be used as a nanovehicle for immobilization of anticancer medicines and to integrate them at a target site. The anticancer medicines doxorubicin (DOX) and methotrexate (MTX) were immobilized separately and in combination onto MNP by a glutaraldehyde activation method and confirmed by magnetic nanoparticles linked immunosorbent assay (MagLISA) and Fourier-transform infrared (FTIR) spectroscopy. The phenol peaks of DOX and MTX at 2896.6 cm⁻¹ to 2912.5 cm⁻¹ in FTIR spectra of immobilized medicines indicated the conjugation. Affinity-purified anti-DOX and anti-MTX antibodies were used to evaluate the coupling of DOX and MTX onto MNP, and the binding was found 34.6% to 37.2% and 51.8% to 54.3% separately, respectively. The immobilization of DOX and MTX in combination onto MNP was 18% and 27%, respectively. HeLa and B cells were cultured with DOX-MNP, MTX-MNP, and DOX-MNP-MTX separately, and MagLISA indicated that the binding of DOX-MNP/MTX-MNP was 41.5% to 45% with HeLa cells and 20% to 26% with B cells. No significant difference was observed in binding of DOX-MNP-MTX with HeLa and B cells. Results also indicated that the release of medicines at pH 5.0 is more (39% to 44%) than at pH 7.4 (3.7% to 10.2%). Sixteen to 22% more killing effect was observed on HeLa cells than on B cells. In immunohistochemical staining, more deposition of brown color on HeLa cells than on B cells may be due to more expression of iron-binding sites on cancer cells. The dual property of MNP can be used for binding of medicines and for targeting drug delivery.