Nonlinear effects of nanoparticles: biological variability from hormetic doses, small particle sizes, and dynamic adaptive interactions.

Researchers are increasingly focused on the nanoscale level of organization where biological processes take place in living systems. Nanoparticles (NPs, e.g., 1-100 nm diameter) are small forms of natural or manufactured source material whose properties differ markedly from those of the respective bulk forms of the "same" material. Certain NPs have diagnostic and therapeutic uses; some NPs exhibit low-dose toxicity; other NPs show ability to stimulate low-dose adaptive responses (hormesis). Beyond dose, size, shape, and surface charge variations of NPs evoke nonlinear responses in complex adaptive systems. NPs acquire unique size-dependent biological, chemical, thermal, optical, electromagnetic, and atom-like quantum properties. Nanoparticles exhibit high surface adsorptive capacity for other substances, enhanced bioavailability, and ability to cross otherwise impermeable cell membranes including the blood-brain barrier. With super-potent effects, nano-forms can evoke cellular stress responses or therapeutic effects not only at lower doses than their bulk forms, but also for longer periods of time. Interactions of initial effects and compensatory systemic responses can alter the impact of NPs over time. Taken together, the data suggest the need to downshift the dose-response curve of NPs from that for bulk forms in order to identify the necessarily decreased no-observed-adverse-effect-level and hormetic dose range for nanoparticles.