Abstract:
Over the past few years, nanotechnology-based
approaches have emerged to override drug resistance owing to
their superiority over other formulations because of their diverse
therapeutic advantages such as target-specific drug delivery,
enhanced bioavailability, biodegradability, and minimal off-target
effects. Hybrid nanomaterials as a formulation of anticancer drugs
with gold nanoparticles (AuNPs) have adequately proven
efficacious in controlled release as well as disintegration into
ultrasmall nanoparticles dragging the drug to penetrate deep into
tumor tissues and consequently getting cleared from the body. In
this study, to achieve better antitumor responses, we engineered
self-assembled organic nanoparticles of potent anticancer compound BZ6 (BZ6-ONPs), BZ6-gold nanoparticle conjugates (BZ6-
AuNPs), and organic−inorganic nanohybrids involving amalgamation of AuNPs with BZ6-ONPs (AuNPs@BZ6-ONPs) and
comparatively analyzed their physicochemical as well as biological activities. The epithelial−mesenchymal transition (EMT) is a
critical biological event that facilitates metastatic spread of cancer cells and contributes to chemoresistance. AuNPs@BZ6-ONPs
consistently suppressed EMT characteristics including invasion, cell scattering, and migration abilities of aggressive breast cancer
(MDA-MB-231) and pancreatic adenocarcinoma (PANC-1) cells much more efficiently than BZ6-ONPs and BZ6-AuNPs. Western
blotting and immunocytochemistry analysis unveiled that the nanohybrids downregulated expression of the key mesenchymal
markers NF-κβ p65, Twist-1, vimentin, and MMP-2, meanwhile augmenting epithelial marker E-cadherin and tumor suppressor Par4. The in vivo syngenic mouse tumor model demonstrated remarkable reduction of tumor growth (84.3%) and metastatic lung
nodules (66.1%) following 14 days of treatment without any adverse effects. Finally, the facile and ecofriendly method of synthesis of
AuNPs@BZ6-ONPs demonstrating promising antitumor/antimetastatic efficacies suggests its therapeutic implication for the
treatment of advanced cancers.
