PEGylated liposomes: immunological responses

Marwa Mohamed, Amr S. Abu Lila, Taro Shimizu, Eman Alaaeldin, Amal Hussein, Hatem A. Sarhan, Janos Szebeni, Tatsuhiro Ishida

Research output: Contribution to journalReview article

9 Citations (Scopus)


A commonly held view is that nanocarriers conjugated to polyethylene glycol (PEG) are non-immunogenic. However, many studies have reported that unexpected immune responses have occurred against PEG-conjugated nanocarriers. One unanticipated response is the rapid clearance of PEGylated nanocarriers upon repeat administration, called the accelerated blood clearance (ABC) phenomenon. ABC involves the production of antibodies toward nanocarrier components, including PEG, which reduces the safety and effectiveness of encapsulated therapeutic agents. Another immune response is the hypersensitivity or infusion reaction referred to as complement (C) activation-related pseudoallergy (CARPA). Such immunogenicity and adverse reactivities of PEGylated nanocarriers may be of potential concern for the clinical use of PEGylated therapeutics. Accordingly, screening of the immunogenicity and CARPA reactogenicity of nanocarrier-based therapeutics should be a prerequisite before they can proceed into clinical studies. This review presents PEGylated liposomes, immunogenicity of PEG, the ABC phenomenon, C activation and lipid-induced CARPA from a toxicological point of view, and also addresses the factors that influence these adverse interactions with the immune system.

Original languageEnglish
Pages (from-to)710-724
Number of pages15
JournalScience and Technology of Advanced Materials
Issue number1
Publication statusPublished - Dec 31 2019



  • Accelerated blood clearance (ABC) phenomenon
  • PEGylated liposomes
  • anti-PEG IgM
  • complement activation
  • complement activation-related pseudoallergy (CARPA)
  • hypersensitivity reactions (HSRs)
  • polyethylene glycol (PEG)

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Mohamed, M., Abu Lila, A. S., Shimizu, T., Alaaeldin, E., Hussein, A., Sarhan, H. A., Szebeni, J., & Ishida, T. (2019). PEGylated liposomes: immunological responses. Science and Technology of Advanced Materials, 20(1), 710-724.