Effects of inorganic nanoparticles on liver fibrosis: Optimizing a double-edged sword for therapeutics

Liver fibrosis is a condition of sustained wound healing in response to chronic liver injury caused by various factors such as viral, cholestatic and inflammatory diseases. Despite significant advances in the understanding of the mechanistic details of fibrosis, therapeutic intervention with the use of anti-fibrotic drugs achieved only marginal efficacy. Among which, pharmacokinetics profile of agents leading to off-targeting and suboptimal distribution are the principal limiting factors. Concurrently, inorganic nanoparticles (NPs) have gained significant recognition in biomedicine, owning to their unique physicochemical properties. Since NPs are known to accumulate in well vascularised organs, the intuitive therapeutic targeting of the liver using engineered NPs seems to be a plausible approach in treating liver fibrosis. However, the application of inorganic NPs also raised concerns of its potential long-term impact to humans. Current literatures have reported both negative risks as well as surprising benefits, thus sparking off a needful discussion about the feasibility of using inorganic NPs in treating liver fibrosis. Inorganic NPs entrapped in the liver may pose health risks, particularly due to their non-biodegradability and potential toxicity when accumulated in undesirable concentrations. This highlighted the need to assess the health risk of using inorganic NPs, and also to establish a framework to evaluate the conditions when the beneficial effects of these NPs would outweigh potential risks. Hence, this review takes a balanced approach on assessing the mechanistic details behind inorganic NP-induced biochemical perturbations, which could either alleviate or worsen liver fibrosis. Consequently, it attempts to chart out possibilities for future directions through optimizing therapeutic outcomes by design.