Curcumin-based Nanoformulation for the Pyroptotic Death of MDA-MB-231 Cells

Curcumin (CU), a diphenolic natural flavonoid, has been considered as a next -generation anticancer agent; however, its efficacy is hindered by poor selectivity and low bioavailability (<3 x 10(-8) mu M). Nanoformulation becomes a promising strategy for the target-specific delivery of flavonoid, wherein nanoformulation itself exhibits multiple therapeutic and diagnostic modalities. Presently, we have developed CU and Prussian blue nanocube (PBNC)-based nanoformulation which shows chemo-phototoxicity against triple -negative breast cancer (TNBC, ca. MDA-MB-231 cell line) but possesses compatibility against normal HEK-293 cells up to a concentration of similar to 42 +/- 2.1 mu g/mL. We have validated the dual -mode T1-T2 weighted magnetic resonance imaging (MRI) capability of the nanoformulation having relaxivity parameters r1 similar to 6.01 mM(-1) s(-1) and r(2)similar to 15.89 mM(-1) s(-1 )under a clinical magnetic field of 3 T, higher than relaxivity parameters of commercially available MRI contrast agents [MAGNEVIST (r1 similar to 3.1 mM(-1) s(-1), r(2)similar to 3.7 mM(-1) s(-1)), GADOVIST (r1 similar to 3.2 mM(-1) s(-1), r(2)similar to 3.9 mM(-1) s(-1)), and PROHANCE (r1 similar to 2.8 mM(-1) s(-1), r(2)similar to 3.2 mM(-1) s(-1) etc.]. Meanwhile, the size dependence of relaxivity parameters is dependent on crystal inhomogeneity and magnetization. In the therapeutic part, we have noticed oxidative stress-induced pyroptotic cell death, indexed by the expression of series of proteins including P2RX7-CASPASE1 and IL-1 beta-NLRP3. Smaller-sized particles show better theranostic activity due to easy internalization. In summary, our study suggests that PBNC (similar to 60 nm) is highly beneficial to deliver CU, while our conceptual study clearly demonstrates the role of size and functionalization on its theranostic properties.