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

Abstract

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 × 10 −8 μM). 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 ∼42 ± 2.1 μg/mL. We have validated the dual-mode T 1 −T 2 weighted magnetic resonance imaging (MRI) capability of the nanoformulation having relaxivity parameters r 1 ∼ 6.01 mM −1 s −1 and r 2 ∼ 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 (r 1 ∼ 3.1 mM −1 s −1 , r 2 ∼ 3.7 mM −1 s −1 ), GADOVIST (r 1 ∼ 3.2 mM −1 s −1 , r 2 ∼ 3.9 mM −1 s −1 ), and PROHANCE (r 1 ∼ 2.8 mM −1 s −1 , r 2 ∼ 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-1β-NLRP3. Smaller-sized particles show better theranostic activity due to easy internalization. In summary, our study suggests that PBNC (∼60 nm) is highly beneficial to deliver CU, while our conceptual study clearly demonstrates the role of size and functionalization on its theranostic properties.