Modified mesoporous silica nanocarriers containing superparamagnetic iron oxide nanoparticle, 5-fluorouracil or oxaliplatin, and metformin as a radiosensitizer, significantly impact colorectal cancer radiation therapy.

Autor: Khalili-Hezarjaribi H; Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran., Bahrami AR; Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran; Industrial Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran., Sh Saljooghi A; Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran; Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran., Matin MM; Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran; Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran. Electronic address: matin@um.ac.ir.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Dec 05; Vol. 666, pp. 124838. Date of Electronic Publication: 2024 Oct 16.
DOI: 10.1016/j.ijpharm.2024.124838
Abstrakt: This study investigates the anticancer effects of SPION-based silica nanoparticles carrying 5-fluorouracil (5-FU) or oxaliplatin (OX), and metformin (MET) on colorectal cancer cells. Nanocarriers were equipped with pH-responsive gold gatekeepers for controlled release, PEGylation for longer circulation, and folic acid (FA) for targeted delivery. The effects were evaluated by investigating cell viability, cellular uptake, flow cytometry, and clonogenic assay in vitro. The efficacy of the system was also tested in vivo on C57BL/6 mice bearing HT-29 tumors, and potential side effects were evaluated. Nanocarriers were synthesized with hydrodynamic diameters of 79.8 nm for 5-FU and 85.2 nm for OX; zeta potentials of -21 and -22 mV, respectively, and remained stable after 72 h. Encapsulation efficiencies were 85 % for 5-FU, 80 % for OX, and 83 % for MET, with loading capacities of 44 %, 38 %, and 41 %, respectively. Drug release in acidic buffer was 38.7 % for 5-FU, 32.8 % for OX, and 43.5 % for MET. MTT assay showed increased toxicity due to FA conjugation, while PEGylation reduced the hemolysis activity. Targeted nanocarriers demonstrated superior cellular uptake and tumor localization compared to non-targeted variants. The combination of 5-FU-MET and OX-MET nanocarriers with radiation therapy (RT) demonstrated the greatest effect on their antitumor activity, accompanied by minimal side effects indicating effective tumor targeting in vivo. MRI and CT imaging further supported these findings. This study underscores the synergistic impact of MET alongside RT on the inhibition of cancer cells and tumor growth for both targeted 5-FU and OX nanocarriers reflecting the significant radiosensitizing properties of MET.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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