Magnetic Targeting of 5-Fluorouracil-Loaded Liposome-Nanogels for In Vivo Breast Cancer Therapy and the Cytotoxic Effects on Liver and Kidney

Ulker D., Ozyurt R., ERKASAP N., BÜTÜN V.

AAPS PharmSciTech, cilt.23, sa.8, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 23 Sayı: 8
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1208/s12249-022-02438-y
  • Dergi Adı: AAPS PharmSciTech
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, EMBASE, International Pharmaceutical Abstracts, MEDLINE
  • Anahtar Kelimeler: breast cancer, controlled drug delivery, cytotoxicity, liposome, magnetic carriers, magnetic targeting, CONTROLLED DRUG-DELIVERY, THYMIDYLATE SYNTHASE, MOLECULAR-MECHANISMS, MULTIDRUG-RESISTANCE, NANOPARTICLES, CHEMOTHERAPY, SYSTEM, MCF7, FUNCTIONALIZATION, CHEMORESISTANCE
  • Eskişehir Osmangazi Üniversitesi Adresli: Evet

Özet

© 2022, The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.In our previous paper, we demonstrated the ex vivo studies of non-toxic liposome-nanogel systems by which the long-term drug release could be provided from hybrid systems for the 5-fluorouracil (5-FU) drug molecule. The aim of this study was the in vivo magnetic targeting of 5-FU-loaded Fe3O4 nanoparticles including DPPC liposome-based PEGylated nanogels (5-FU loaded Fe3O4LPN) to breast cancer tissue and the investigation of the treatment and cytotoxic effects of that hybrid system to the liver and kidney in CD-1 mice using an external magnetic field. The effectiveness of the control, 5-FU group, Fe3O4LPN, and 5-FU-loaded Fe3O4LPN systems was evaluated using histopathology in terms of p53, ESR, PRG and C-erB-2, and qRT-PCR in terms of TYMS, ESR-1, RPG, and EGRF. Also, the cytotoxicity was analyzed by histopathological evaluation of kidney and liver tissues. Caspase-3 and caspase-9 evaluations were performed by qRT-PCR. The creatinine and ALT levels were also evaluated by comparing the blood samples of all groups. A total of 300-nm TEM-sized Fe3O4LNP hybrid system was successfully prepared. That system significantly decreased the TYMS and ESR1 levels after treatment process and increased the levels of p53 expression. The levels of caspase-3 mRNA did not change during the treatment, but the level of caspase-9 mRNA level was significantly decreased. The magnetically targeted liposome-based nanogel hybrid system is promising an effective therapy for the breast tumor with less liver and kidney damage. This Fe3O4LNP hybrid system could be useful for the similar small molecules. Graphical Abstract: [Figure not available: see fulltext.]