Nanoparticle Behavior in the Body: Biochemical, Pharmacological and Cellular Aspects

The behavior of nanoparticles (NPs) in the body is a complex, multilevel process governed by a cascade of physicochemical and biological interactions. At the molecular level, these processes include protein adsorption and formation of the biomolecular corona, ion release, and surface redox reactions. At the cellular level, they encompass endocytosis, intracellular trafficking, lysosomal processing and clearance, and redistribution within cellular compartments. At the systemic level, NPs undergo tissue and organ biodistribution, biological barrier crossing, biotransformation, biodegradation, elimination, and immunomodulation. Understanding these processes is essential for evaluating the safety, efficacy, and therapeutic potential of nanomedicines, as the unique physicochemical properties of NPs can induce biological responses that differ substantially from those of their bulk counterparts. This review provides an integrated framework for understanding the absorption, distribution, biotransformation, and elimination of NPs in biological systems. Particular emphasis is placed on the molecular and cellular mechanisms governing nanoparticle–biological interactions, including the effects of NPs on cellular energy metabolism through interactions with the mitochondrial electron transport chain and their immunomodulatory effects mediated by nuclear factor κB (NF-κB) signaling and inflammasome activation. By integrating molecular, cellular, and systemic perspectives, this review highlights the key determinants of nanoparticle fate in the body and their implications for the design, safety, and clinical translation of nanomedicines.