Polymeric micelles loaded with (1,2-diaminocyclohexane)platinum(II) against colorectal cancer
| Autor: | Takako Nirei, Toshiaki Watanabe, Soichiro Ishihara, Toshiaki Tanaka, Kazushige Kawai, Keisuke Hata, Tomomichi Kiyomatsu, H. Nozawa |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Pathology
medicine.medical_specialty Organoplatinum Compounds Colorectal cancer Aspartate transaminase Antineoplastic Agents 02 engineering and technology Adenocarcinoma Pharmacology Metastasis Mice Random Allocation 03 medical and health sciences chemistry.chemical_compound Liver Neoplasms Experimental 0302 clinical medicine Cell Line Tumor medicine Animals Distribution (pharmacology) Adverse effect Micelles Mice Inbred BALB C Creatinine biology business.industry 021001 nanoscience & nanotechnology medicine.disease Oxaliplatin Alanine transaminase chemistry 030220 oncology & carcinogenesis biology.protein Surgery Drug Screening Assays Antitumor Colorectal Neoplasms 0210 nano-technology business medicine.drug |
| Zdroj: | Journal of Surgical Research. 218:334-340 |
| ISSN: | 0022-4804 |
| DOI: | 10.1016/j.jss.2017.06.056 |
| Popis: | Background We investigated the potential of nanomedicine in loading the oxaliplatin parent complex (1,2-diaminocyclohexane)platinum(II)-loaded polymeric micelles (DACHPt/m) against multiple liver metastases from colon cancer in a mouse model. Materials and methods The efficacy of DACHPt/m or oxaliplatin (on days 14 and 21 after inoculation of tumor cells) was evaluated in a mouse model of liver metastasis for murine colon adenocarcinoma C26 cells. In vivo antitumor effects were evaluated by recording the number of liver metastases and weights of metastatic livers after treatment (day 28). The accumulation of drugs in tumors and liver parenchyma was analyzed using ion coupled plasma-mass spectrometry 24 h after administration of DACHPt/m or oxaliplatin ( n = 5). We assessed renal and hepatic toxicities through changes in creatinine, aspartate transaminase, and alanine transaminase on the last day of the antitumor activity experiment. Results Mice receiving DACHPt/m had significantly fewer metastatic nodules ( P = 0.038) and lower liver weights ( P = 0.038) than those receiving oxaliplatin. The accumulation of DACHPt/m in the metastatic liver was significantly higher than that of oxaliplatin, whereas the distribution of micelles in healthy liver tissues was limited. Mice treated with DACHPt/m also showed significantly lower serum creatinine levels than those treated with oxaliplatin ( P = 0.007), whereas serum aspartate transaminase and alanine transaminase levels for both drugs were not different. Conclusions High levels of DACHPt/m accumulate in metastatic livers, producing a strong antitumor effect without severe adverse effects. DACHPt/m is a safe approach for managing liver metastasis from colorectal cancer. |
| Databáze: | OpenAIRE |
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