J Cancer 2020; 11(23):6982-6991. doi:10.7150/jca.48528 This issue

Research Paper

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

Venkateswara R Gogineni1, Dilip R Maddirela1, Wooram Park2, Jaidip M Jagtap1, Abdul K Parchur1, Gayatri Sharma1, El-Sayed Ibrahim1, Amit Joshi1, Andrew C Larson2, Dong-Hyun Kim2, Sarah B White1✉

1. Departments of Radiology & *Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI.
2. Department of Radiology, Northwestern University, Chicago, IL.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Gogineni VR, Maddirela DR, Park W, Jagtap JM, Parchur AK, Sharma G, Ibrahim ES, Joshi A, Larson AC, Kim DH, White SB. Localized and triggered release of oxaliplatin for the treatment of colorectal liver metastasis. J Cancer 2020; 11(23):6982-6991. doi:10.7150/jca.48528. Available from https://www.jcancer.org/v11p6982.htm

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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- Fe3O4/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-Fe3O4/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-Fe3O4/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- Fe3O4/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.

Keywords: hybrid liposome-magnetic nanoparticles, oxaliplatin, colorectal liver metastases