The role of stem cells in the pharmacological assessment of nanoparticles

Stem cells aid in the pharmacological assessment of nanoparticles by serving as a human-relevant, dynamic, and scalable model. Their integration into nanoparticle research enhances toxicity screening and therapeutic optimization by evaluating absorption, distribution, metabolism, excretion and toxicity (ADMET) parameters across models ranging from simple in vitro cultures to complex organoids. They provide insights into how nanoparticles interact with biological systems, guiding the rational design of safer, more effective nanomedicines. Conventional in vitro and animal models often fall short in recapitulating human-specific responses, as they cannot fully capture the complex interactions between nanoparticles and biological systems. This limitation significantly reduces the predictive accuracy of toxicity and efficacy assessments. In contrast, stem cell-based models offer a transformative platform by providing physiologically relevant, patient-specific and organotypic systems which help overcome critical challenges such as species differences, limited cellular diversity, and ethical concerns associated with animal testing. This review examines the fundamentals of nanoparticle and stem cell interactions, ADMET profiling, and the immunomodulatory properties of nanoparticles, all of which are pivotal for comprehensive pharmacological assessment. The key challenges such as standardization, long-term safety, and regulatory compliance that hinder clinical translation are also discussed. • Stem cells provide a valuable platform for evaluating nanoparticle ADMET properties. • NP physicochemical traits and uptake pathways influence stem cell differentiation. • NPs can either stimulate or suppress immunity based on their physicochemical properties.