Localized and triggered release of oxaliplatin for the treatment of colorectal liver metastasis.

Autor: Gogineni VR; Departments of Radiology & Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI., Maddirela DR; Departments of Radiology & Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI., Park W; Department of Radiology, Northwestern University, Chicago, IL., Jagtap JM; Departments of Radiology & Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI., Parchur AK; Departments of Radiology & Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI., Sharma G; Departments of Radiology & Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI., Ibrahim ES; Departments of Radiology & Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI., Joshi A; Departments of Radiology & Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI., Larson AC; Department of Radiology, Northwestern University, Chicago, IL., Kim DH; Department of Radiology, Northwestern University, Chicago, IL., White SB; Departments of Radiology & Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI.
Jazyk: angličtina
Zdroj: Journal of Cancer [J Cancer] 2020 Oct 12; Vol. 11 (23), pp. 6982-6991. Date of Electronic Publication: 2020 Oct 12 (Print Publication: 2020).
DOI: 10.7150/jca.48528
Abstrakt: Purpose: The aim of this study was to develop and evaluate a liposome formulation that deliver oxaliplatin under magnetic field stimulus in high concentration to alleviate the off-target effects in a rat model of colorectal liver metastases (CRLM). Materials and Methods: Hybrid liposome-magnetic nanoparticles loaded with Cy5.5 dye and oxaliplatin (L-NIR- Fe 3 O 4 /OX) were synthesized by using thermal decomposition method. CRLM (CC-531) cell viability was assessed and rats orthotopically implanted with CC-531 cells were treated with L-NIR-Fe 3 O 4 /OX or by drug alone via different routes, up to 3 cycles of alternating magnetic field (AMF). Optical and MR imaging was performed to assess the targeted delivery. Biodistribution and histology was performed to determine the distribution of oxaliplatin. Results: L-NIR-Fe 3 O 4 /OX presented a significant increase of oxaliplatin release (~18%) and lower cell viability after AMF exposure ( p <0.001). Optical imaging showed a significant release of oxaliplatin among mesenteric vein injected (MV) group of animals. MR imaging on MV injected animals showed R2* changes in the tumor regions at the same regions immediately after infusion compared to the surrounding liver ( p <0.001). Biodistribution analysis showed significantly higher levels of oxaliplatin in liver tissues compared to lungs ( p <0.001) and intestines ( p <0.001) in the MV animals that received AMF after L-NIR- Fe 3 O 4 /OX administration. Large tumor necrotic zones and significant improvement in the survival rates were noted in the MV animals treated with AMF. Conclusion: AMF triggers site selective delivery of oxaliplatin at high concentrations and improves survival outcomes in colorectal liver metastasis tumor bearing rats.
Competing Interests: Competing Interests: The authors have declared that no competing interest exists.
(© The author(s).)
Databáze: MEDLINE
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