The use of styrene Maleic Acid nanomicelles encapsulating the synthetic cannabinoid analog WIN55,212-2 for the treatment of triple negative breast cancer

Breast cancers are the most common cancers diagnosed in women. The therapeutic decision relies primarily on the level of expression of three protein biomarkers namely: estrogen receptor-α (ER-α), progesterone receptor (PR), and HER2. These biomarkers are essential determinants of breast cancer biology, have guided the therapeutic strategies, and predicted the response to systemic therapies.

Triple-negative breast cancers (TNBC), lacking the expression of these three biomarkers, continue to experience the highest mortality rate. Synthetic cannabinoid WIN55,212-2 (WIN) has shown promise as an anticancer agent but causes psychoactive side-effects.

In the present study, nano-micelles of styrene maleic acid (SMA)-conjugated WIN were synthesized to reduce side-effects and increase drug efficacy against triple negative breast cancer. Pharmacokinetics studies revealed the lower brain concentrations levels of WIN formulated Nano micelles, accompanied by almost 3 folds increase in its concentration levels in cancer tissues compared to free WIN. SMA-WIN formulation reduced tumor growth with milder psychoactive side effects when compared to the free drug. Moreover, low dosage of SMA-WIN, almost devoid of psychoactive side effects, in combination with an established chemotherapeutic agent achieved therapeutic efficacy and was sufficient to reduce the tumor volume of TNBC murine cancer model drastically.

Author(s): Khaled Greish a, Aanchal Mathur a, Reem Al Zahrani a, Sara Elkaissi a, Muna Al Jishi a, Osama Nazzal a, Safa Taha a, Valeria Pittalà b and Sebastien Taurin a

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