Nanobiotechnology for health-care

Therapeutic potential of BMN 673 loaded solid lipid nanoparticles in triple negative breast cancer
Guney Eskiler G.1, Cecener G.2, Dikmen G.3, Egeli U.2, Tunca B.2

1 Medical Biology Department, University of Sakarya, Sakarya, Turkey. 
E-mail: gamzeguney@sakarya.edu.tr
2 Medical Biology Department, University of Uludag, Bursa, Turkey.
3 Central Research Laboratory Application and Research Center (ARUM), University of Eskisehir Osmangazi, Eskisehir, Turkey.

BMN 673 (Talozoparib) is the most potent and specific inhibitor of PARP1/2 in for the treatment of BRCA1/2 defective breast cancer. However, the broad utility of BMN 673 has been limited by acquired resistance and its pharmacokinetic/pharmacodynamics properties [1,2]. Solid lipid nanoparticles (SLNs) have attracted great attention as a potential drug delivery system due to unique properties [3]. In the current study, we aimed to produce BMN 673 loaded SLNs formulation to improve these drawbacks and determine in vitro cytotoxic and apoptotic effects (0.01-10 nM) on BRCA1 defective HCC1937 triple negative breast cancer and MCF-10A mammary epithelial control cells.
BMN 673-SLNs were spherically shaped, size in the diameter range of 220 to 355 nm at 4, 25 and 40 ºC and more stable than BMN 673. HCC1937 cell viability was significantly decreased to 35.0% and 29.0% (p<0.01) at a dose of 10 nM BMN 673 and BMN 673-SLNs for 12 days, respectively. In contrast, the percentage of viable cells decreased by around 40.0% and 64.0% in MCF-10A cells upon treatment with 10 nM BMN 673 and BMN 673-SLNs for 12 days, respectively. The total apoptotic rates of HCC1937 and MCF-10A cells increased by 89.9% and 33.2% at 10 nM BMN 673-SLNs for 12 days, respectively (p<0.01). Additionally, BMN 673-SLNs had an even greater anti-migratory effect and remarkably reduced colony formation than BMN 673 in HCC1937 cells. In conclusion, in vitro results demonstrated that the delivery of BMN 673 by SLNs increased its therapeutic potential and induced apoptosis, as well as reduced toxic effects on control cells.
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