Evaluation of SMA-RL71, a curcumin analogue nanomicelle as a drug in xenograft models of triple negative breast cancer
Triple negative breast cancer (TNBC) is a subtype of ER (-) cancer that currently has no treatment options. A novel drug formulation of the most potent curcumin analogue (RL71), compared to the analogues synthesised by other laboratories, styrene-co-maleic acid - 3,5-bis (3,4,5-trimethoxybenzylidene)-1 methylpiperidin-4-one (SMA-RL71) was tested for its anti-cancer activity in an animal model of breast cancer. In the dose response study 15 mg/kg, 10 mg/kg and 5 mg/kg of SMA-RL71 and 10 mg/kg of RL71 was injected into the tail vein of female SCID mice inoculated with MDA-MB-231 cells. None of the treatments produced a statistically significant decrease in tumour volume. Since SMA-RL71 15 mg/kg caused necrosis of the tail, a time course study was performed using SMA-RL71 10 mg/kg at different time points to test if tumour suppression could be achieved with multiple injections of the drug. Mice were randomly grouped after tumour inoculation and dosed with SMA-RL71 10 mg/kg (2 weeks), SMA-RL71 10 mg/kg (3 weeks), RL71 10 mg/kg (2 weeks), and RL71 10 mg/kg (3 weeks) via the tail vein, twice weekly (every 3-4 days). Tumour volume and body weight were determined twice weekly and tumour weight was determined at necropsy. Toxicity was determined from the organ weight at the time of necropsy. Compared to control, there was a 46% decrease (P < 0.001) in tumour volume in the mice dosed with SMA-RL71 10 mg/kg for 2 weeks from day 24. Furthermore, on day 31 when the mice were sacrificed, there was a 43% decrease (P < 0.0001) in tumour weight. All mice gained a similar amount of weight at the end of each study. However, an increase in the weight of the spleen, liver and kidney were observed in the mice dosed with SMA-RL71. HPLC was optimised for the detection of RL71 in plasma, using curcumin as an internal standard. In summary, 15% SMA-RL71 10 mg/kg twice weekly for two weeks suppressed the growth of TNBC tumours without any significant loss in body weight.
Advisor: Rosengren, Rhonda
Degree Name: Master of Science
Degree Discipline: Pharmacology and Toxicology
Publisher: University of Otago
Keywords: Breast; cancer; EPR; curcumin; analogue; nanomicelle; SMA-RL71
Research Type: Thesis