Encapsulating Naringenin in biomimetic proteolipid vesicles abrogates cancer metastasis by targeting apoptotic signaling axis

Naringenin (NG) belongs to the class of flavanones having impressive pharmacological properties. Unfortunately, the in vivo bioavailability of NG is very low due to its higher hydrophobicity, which limits its practical use. Thus, in this study, we tried to develop NG-loaded macrophage membrane-coated liposome-based biomimetic nanoparticles with distinct physicochemical compositions and biological attributes for improving their bioavailability at the target site. The developed biomimetic nanoparticle (BNP) has shown good biocompatibility, stability, satisfactory particle size, pH-responsive drug (NG) release kinetics, and higher cellular uptake in vitro. The anti-metastatic efficacy of NGBNP has confirmed in syngeneic athymic BALB/c nude experimental models. By western blot analysis, semi-quantitative PCR, real-time PCR, and IHC, we conclude that NGBNP gets localized on the metastatic niche via its surface receptor α4, β1 integrin, and VCAM1 of metastatic cells and reduces the number of metastatic colonies in the lungs via regulating the apoptotic signaling axis.