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Expert Opin Drug Deliv. 2015 Jul;12(7):1163-75. doi: 10.1517/17425247.2015.1042857. Epub 2015 May 20.

Strategy for selecting nanotechnology carriers to overcome immunological and hematological toxicities challenging clinical translation of nucleic acid-based therapeutics.

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Principal Scientist, Immunology Section Head,Nanotechnology Characterization Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research , P .O. Box B, Frederick, MD 21702 , USA +1 301 8466939 ; +1 301 846 6399 ;



Clinical translation of nucleic acid-based therapeutics (NATs) is hampered by assorted challenges in immunotoxicity, hematotoxicity, pharmacokinetics, toxicology and formulation. Nanotechnology-based platforms are being considered to help address some of these challenges due to the nanoparticles' ability to change drug biodistribution, stability, circulation half-life, route of administration and dosage. Addressing toxicology and pharmacology concerns by various means including NATs reformulation using nanotechnology-based carriers has been reviewed before. However, little attention was given to the immunological and hematological issues associated with nanotechnology reformulation.


This review focuses on application of nanotechnology carriers for delivery of various types of NATs, and how reformulation using nanoparticles affects immunological and hematological toxicities of this promising class of therapeutic agents.


NATs share several immunological and hematological toxicities with common nanotechnology carriers. In order to avoid synergy or exaggeration of undesirable immunological and hematological effects of NATs by a nanocarrier, it is critical to consider the immunological compatibility of the nanotechnology platform and its components. Since receptors sensing nucleic acids are located essentially in all cellular compartments, a strategy for developing a nanoformulation with reduced immunotoxicity should first focus on precise delivery to the target site/cells and then on optimizing intracellular distribution.


drug delivery; immunotoxicity; nanoparticles; nucleic acid therapeutics

[Indexed for MEDLINE]

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