Nanomedicine involves the use of nanoparticles for therapeutic and diagnostic purposes. During the past two decades,
a growing number of nanomedicines have received regulatory approval and many more show promise for future clinical
translation. In this context, it is important to evaluate the safety of nanoparticles in order to achieve biocompatibility and desired
activity. However, it is unwarranted to make generalized statements regarding the safety of nanoparticles, since the field
of nanomedicine comprises a multitude of different manufactured nanoparticles made from various materials. Indeed, several
nanotherapeutics that are currently approved, such as Doxil and Abraxane, exhibit fewer side effects than their small molecule
counterparts, while other nanoparticles (e.g. metallic and carbon-based particles) tend to display toxicity. However, the
hazardous nature of certain nanomedicines could be exploited for the ablation of diseased tissue, if selective targeting can be
achieved. This review discusses the mechanisms for molecular, cellular, organ, and immune system toxicity, which can be
observed with a subset of nanoparticles. Strategies for improving the safety of nanoparticles by surface modification and pretreatment
with immunomodulators are also discussed. Additionally, important considerations for nanoparticle safety assessment
are reviewed. In regards to clinical application, stricter regulations for the approval of nanomedicines might not be required.
Rather, safety evaluation assays should be adjusted to be more appropriate for engineered nanoparticles.