Genomic perspectives in inter-individual adverse responses following nanomedicine administration: The way forward.
The underlying mechanism of intravenous infusion-related adverse reactions inherent to regulatory-approved nanomedicines still remains elusive. There are substantial inter-individual differences in observed adverse reactions, which may include cardiovascular, broncho-pulmonary, muco-cutaneous, neuro-psychosomatic and autonomic manifestations. Although nanomedicine-mediated triggering of complement activation has been suggested to be a significant contributing factor to these adverse events, complement activation may still proceed in non-responders. Whether these reactions share similar immunological mechanisms and underpinning genetic factors with drug hypersensitivity syndrome remains to be investigated. Genetic association studies could be a powerful tool to dissect causative factors and reveal the multiple molecular pathways that induce infusion related adverse reactions. It is envisaged that such research may lead to the design of reliable in vitro profiling tests for risk assessment and treatment decisions, thereby revolutionizing the practice of medicine with nanopharmaceuticals. Such procedures may further improve regulatory approval processes for nanomedicines currently in the pipeline and decrease the overall cost of health care. Here we discuss some key innate immunity genes and their polymorphisms in relation to nanomedicine infusion-mediated symptomatic responses.
Centre for Pharmaceutical Nanotechnology and Nanotoxicology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark. momo@farma.ku.dk
S Moein
SM
Moghimi
Peter P
PP
Wibroe
Shen Y
SY
Helvig
Z Shadi
ZS
Farhangrazi
A Christy
AC
Hunter
D000818:Animals; D064420:Drug-Related Side Effects and Adverse Reactions; D023281:Genomics; D006801:Humans; D007262:Infusions, Intravenous / Q000009:adverse effects; D050997:Nanomedicine; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D011110:Polymorphism, Genetic
D004364:Pharmaceutical Preparations