In
recent years, the use of silver nanoparticles (AgNPs) in biomedical
applications has shown an unprecedented boost along with simultaneous
expansion of rapid, high-yielding, and sustainable AgNP synthesis
methods that can deliver particles with well-defined characteristics.
The present study demonstrates the potential of metal-tolerant soil
fungal isolate Penicillium shearii AJP05
for the synthesis of protein-capped AgNPs. The particles were characterized
using standard techniques, namely, UV–visible spectroscopy,
transmission electron microscopy, X-ray diffraction, and Fourier transform
infrared spectroscopy. The anticancer activity of the biosynthesized
AgNPs was analyzed in two different cell types with varied origin,
for example, epithelial (hepatoma) and mesenchymal (osteosarcoma).
The biological NPs (bAgNPs) with fungal-derived outer protein coat
were found to be more cytotoxic than bare bAgNPs or chemically synthesized
AgNPs (cAgNPs). Elucidation of the molecular mechanism revealed that
bAgNPs induce cytotoxicity through elevation of reactive oxygen species
(ROS) levels and induction of apoptosis. Upregulation of autophagy
and activation of JNK signaling were found to act as a prosurvival
strategy upon bAgNP treatment, whereas ERK signaling served as a prodeath
signal. Interestingly, inhibition of autophagy increased the production
of ROS, resulting in enhanced cell death. Finally, bAgNPs were also
found to sensitize cells with acquired resistance to cisplatin, providing
valuable insights into the therapeutic potential of bAgNPs. To the
best of our knowledge, this is the first study that provides a holistic
idea about the molecular mechanisms behind the cytotoxic activity
of protein-capped AgNPs synthesized using a metal-tolerant soil fungus.