Recent approaches of toxicity-related attributes of NMs: A systematic review

NMs are becoming a valuable tool for many applications in biomedicine, cosmetics, and agriculture. Because of their compatibility with the nanoscale nature of biological systems, NMs are essential to nanobiotechnology, improving applications including targeted drug delivery, biomedical implants, prosthetics, and diagnostic equipment. NMs enhance medicinal formulations by improving stability and delivery, and strengthen crop resilience in agriculture. While NM offer great benefits, there is growing concerns regarding the potential toxicity due to physicochemical properties such as small size, large surface area, high reactivity. For instance, silver nanoparticles exhibit IC₅₀ values of 14.6 µg/mL (24 h) and 8.3 µg/mL (48 h) in THP-1 cells, whereas ionic Ag⁺ shows greater cytotoxicity (5.3 µg/mL and 2.9 µg/mL, respectively). Shape-dependent effects are also evident, where exposure to differently shaped gold nanoparticles resulted in elevated oxidative stress markers (AST 168 %, SOD 184 %, CAT 137 %), confirming geometry-related toxicity variations. Moreover, advanced lipid-based nanocarriers, such as methotrexate (Methotrexate)-loaded lactoferrin-solid lipid nanoparticles, demonstrated a 70 % reduction in angiogenesis and IC₅₀ = 0.51 µM, highlighting safer-by-design approaches. Different types of NPs show toxicity by the mechanisms such as oxidative stress, inflammatory response, genotoxicity, apoptosis, mitochondrial dysfunction, and membrane damage. Current systematic review provides extensive analysis of toxicity-related attributes of NMs, factor influencing toxicity, and advanced mechanisms of nanotoxicity. Great emphasis is placed on emerging approaches such as omics-based technology, high-throughput screening, organ-on-chip, and in silico modelling of ADMET properties. Regulatory guidelines, standardization efforts, and the challenges inherent to current nanotoxicity assessments are critically reviewed.