*4.3. Anticancer Activity*

In addition to antibacterial and antioxidant activity, metal NPs derived from fungi and other sources have been known to possess outstanding anticancer activity because of their profound ROS generation ability under the dark and light exposure [92,97–99]. Sankar et al. (2013) studied the anticancer activity of AgNPs (~136 nm) derived from *Origanum vulgare* extract against the human lung epithelial cells (A549 cells). AgNPs exhibited dose-dependent toxicity against the A549 cells by 85% inhibition at the dose of 500 µg/mL [100]. Bhat et al. (2013) fabricated Au NPs (12–15 nm, spherical) derived from *P. florida* mushroom extract via the photo-irradiated method and evaluated their anticancer activity against the A-549, MDA-MB, HeLa, and K-562 cell lines. The prepared AuNPs showed concentration-dependent activity against all cell lines in between 10 and 30 µg/mL [48].

Gliga et al. (2014) attempted to understand the coating and size-dependent toxicity of the AgNPs toward the human lung cells (BEAS-2B cells) with an appropriate mechanism. The results confirmed that prepared NPs with size <10 nm showed the highest toxicity against the BEAS-2B cells, which attributes for its aggregation in cell medium, intracellular localization, cellular uptake, and formation of Ag ions intracellularly. However, it is confirmed that all of the AgNPs showed toxicity against BEAS-2B cells via an increase in overall DNA damage within 24 h [101]. In the same year, Yehia and Sheikh (2014) used *P. ostreatus* derived AgNPs (4–15 nm, spherical) as an anticancer agent against the MCF-7 cells. The prepared AgNPs showed dose-dependent cell inhibition ranging from 5% to 78% at concentration 10 to 640 µg/mL [36].

Similarly, in the year 2015, Ismail et al., fabricated AgNPs derived from *P. ostreatus* extract and studied their anticancer effect against the HepG2 and MCF-7 adenocarcinoma cancer cell lines. The authors claimed that NPs induced cytotoxicity toward cancer cells attributes for the formation of ROS species, apoptosis, necrosis, and cell death. ROS are the highly reactive species that result in oxidative damage of proteins, DNA, and induce mitochondrial dysfunction, as summarized in Figure 3 [102]. Similarly, Raman et al. (2015) used *P. djamor* var. roseus derived AgNPs as anticancer agent toward the human prostrate carcinoma PC3 cells [42]. In the year 2013 and 2014, Priyaragini and

Kim et al. demonstrated that metal NPs are harmless at a lower concentration and may be lethal at a higher dose toward normal healthy cells. Many reports revealed the biosynthetic routes to synthesize AgNPs as an anticancer agent against various cell lines. However, AgNPs synthesized using green methods also showed a sort of cytotoxicity against tumor cells [103,104]. Even the extensive use of artificial AgNPs has been already reported, but still, there are limited studies to regulate the cytotoxic effects of AgNPs [36]. Studies on *P. eryngii* (PE) AgNPs showed cytotoxic activity of HeLa with maximum inhibitory effect 73.46% at 60 µg/mL concentration, PC-3 99.02% at 10 µg/mL and MCF-7 cells 93.89% at 20 µg/mL concentration with IC<sup>50</sup> values of 46.594, 2.185, and 6.169 µg/mL, respectively, during a 24-h incubation period [90]. Chaturvedi et al. (2020) studied cytotoxic activity and revealed that the AgNPs and AuNPs mediated from *P. sajor-caju* extract (PS) showed effective results against HCT-116 cancer cell line. HCT-116 cancer cells viability showed inhibition by *P. sajor-caju* extract, Au NPs as well as Ag NPs showing IC<sup>50</sup> value of 60, 80, and 50 µg/mL respectively. The study revealed that the green synthesized AgNPs showed high antiproliferative activity in contrast to other PS extract and Au NPs, and the reason behind the mechanism was due to the generation of more ROS, leading to oxidative stress, resulting in undeviated damage of protein functionality and integrity [60]. The anticancer activity of TiO<sup>2</sup> NPs showed potential toxic effect against human lung cancer (A549) cell lines with maximum inhibited growth of 64% at concentration of 100 µg/mL, after 24 h of exposure [44]. The anticancer activity evaluated from *P. djamor* ZnONPs showed potent inhibitory on A549 cancerous cells with (LC50(Lethal concentration required to kill 50% of population) value as 42.26 µg/mL) in a dose-dependent manner [43].
