期刊
PHARMACEUTICS
卷 12, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics12060589
关键词
Biomimetics; nanoparticles; colon carcinoma; liposome; Oxaliplatin
资金
- Ministerio de Economia y Competitividad from Spain [CGL2016-76723]
- Fondo Europeo de Desarrollo Regional (FEDER) [CGL2016-76723]
- Junta de Andalucia [A-BIO-376-UGR18]
- Unidad Cientifica de Excelencia of the University of Granada [UCE-PP2016-05]
- Conserjeria de Salud de la Junta de Andalucia [PI-0102-2017]
- Instituto de Salud Carlos III (ISCIII) (FEDER) [PI19/01478]
- Andalusian Government [CTS-107]
- Ministerio de Educacion, Ciencia y Deporte y Competitividad (Spain) [FPU16_04580, FPU16_01716]
Current chemotherapy for colorectal cancer (CRC) includes the use of oxaliplatin (Oxa), a first-line cytotoxic drug which, in combination with irinotecan/5-fluorouracil or biologic agents, increases the survival rate of patients. However, the administration of this drug induces side effects that limit its application in patients, making it necessary to develop new tools for targeted chemotherapy. MamC-mediated biomimetic magnetic nanoparticles coupled with Oxa (Oxa-BMNPs) have been previously demonstrated to efficiently reduce the IC(50)compared to that of soluble Oxa. However, their strong interaction with the macrophages revealed toxicity and possibility of aggregation. In this scenario, a further improvement of this nanoassembly was necessary. In the present study, Oxa-BMNPs nanoassemblies were enveloped in phosphatidylcholine unilamellar liposomes (both pegylated and non-pegylated). Our results demonstrate that the addition of both a lipid cover and further pegylation improves the biocompatibility and cellular uptake of the Oxa-BMNPs nanoassemblies without significantly reducing their cytotoxic activity in colon cancer cells. In particular, with the pegylated magnetoliposome nanoformulation (a) hemolysis was reduced from 5% to 2%, being now hematocompatibles, (b) red blood cell agglutination was reduced, (c) toxicity in white blood cells was eliminated. This study represents a truly stepforward in this area as describes the production of one of the very few existing nanoformulations that could be used for a local chemotherapy to treat CRC.
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