Integrin receptor seeking bio-engineered "smart" magnetic nanomaterials in Lewis lung carcinoma toxicity studies
Monika A. Cywińska , Ireneusz P. Grudziński , Anita Kośmider , Magdalena Popławska , Michał Bystrzejewski , Andrzej Cieszanowski , Zbigniew Fijałek , Agnieszka Ostrowska
AbstractNovel self-navigated magnetic nanomaterials are being developed to improve the personalized therapy of cancer through the effective targeted delivery of different biological molecules. Among them, monoclonal antibodies against integrin trans-membrane receptors, a super-family of molecules that mediate both cell-to-cell and cell-to-extracellular matrix signals, have been found to be the innovative drug candidates to be used in both early cancer treatments and cancer diagnosis. In this study, we examined the potential cytotoxicity of the bio-engineered carbon-encapsulated magnetic nanoparticles containing the pre-functionalized carbon surface with monoclonal antibodies recognizing selected integrin receptors. The as-fabricated bio-nanoparticles called “CEMN-MoAbs” were tested for 24 h cytotoxicity studies in murine Lewis lung carcinoma cells (LLC). The 3R-based strategies on CEMN-MoAb nanoparticles (0.0001–100 mcg/ml) were approached using MTT, LDH, Annexin-V/PI, Calcein/PI, JC-1, and cell-cycle analysis. Both TEM and ICP-MS internalization studies were also performed to evidence magnetic nanoparticles bio-distribution in cells. Studies show that CEMN-MoAbs increased mitochondrial and cell membrane cytotoxicity in a dose-dependent manner (MTT/LDH/Calcein/PI). Results also evidence that CEMN-MoAb nanoparticles diminished mitochondrial membrane potentials (JC-1), elevating also some pro-apoptotic events in LLC cells (Annexin-V/PI). Results show that CEMN-MoAb might affect the cell-cycle (cell cycle analysis), and these nanoparticles were widely distributed in cells as determined by TEM/ICP-MS internalization studies. The present results clearly evidence different cellular endpoints for cell membrane, mitochondrial, and nucleus targeted toxicities of monoclonal antibody-navigated carbon-encapsulated magnetic nanoparticles in Lewis lung carcinoma cells.
|Journal series||Toxicology Letters, ISSN 0378-4274|
|Publication size in sheets||4.65|
|Score|| = 35.0, 09-09-2019, ArticleFromJournal|
= 35.0, 09-09-2019, ArticleFromJournal
|Publication indicators||= 0; : 2013 = 1.199; : 2013 = 3.355 (2) - 2013=3.706 (5)|
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