QbD-assisted synthesis and exploration of plasmonic laser activatable nanoGold seeds for photothermal and photodynamic therapy of cancer cells

This investigation aimed to develop fit-to-purpose nanoGold seeds using a quality-by-design approach using 2-level fractional factorial and Box–Behnken design (QbD-approach; 30–40 nm) with exceptional near-infrared laser-responsive surface plasmons resonance properties for photothermal therapy and photodynamic therapy. The synthesized nanoGold seeds were characterized for quality control parameters, and their ability to ablate cancer cells was investigated in 2D monolayer and 3D tumor spheroid in SCC-131 cells. The biomechanics of the anticancer effect was studied by employing various assays. The synthesized nanoGold seeds were found to be spherical in shape within the 30–40 nm size range, showing a strong and reversible photothermal effect with high photothermal indices. Photothermal ablation of cancer cells was observed with cytotoxicity of > 60% in 2D monolayer and > 30% in 3D spheroid and a total apoptotic cell ratio of > 25%. The mRNA levels of BAX, Hsp1A, and PTEN genes were found to be up-regulated by > threefold in each case with NIR laser irradiation. The synthesized nanoGold seeds were found to be hemocompatible and physically stable for 3 months. The interaction between heat and the cytotoxic effect of nanoGold seeds explains its potential role as an alternative and drug-free adjuvant therapy for cancer. Graphical abstract