Cited by 721Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsRNA Interference and Gene Delivery

The accelerated blood clearance (ABC) phenomenon: Clinical challenge and approaches to manage

Abu Lila, Amr S., Kiwada, Hiroshi, Ishida, Tatsuhiro·2013·Journal of Controlled Release

Abstract

Despite the clinical introduction of an increasing number of polyethylene glycol (PEG)-conjugated substances, PEG has been named as the cause of an unexpected immunogenic response known as the "accelerated blood clearance (ABC) phenomenon." This phenomenon has been extensively observed during the repeated administration of PEG-conjugated substances and PEGylated nanocarriers including PEGylated liposomes, PEGylated nanoparticles, PEGylated micelles, etc., resulting in the increased clearance and reduced efficacy of PEG-conjugated substances/PEGylated nanocarriers. In this review, therefore, we focused on the possible mechanisms underlying the induction of such a phenomenon and emphasized the factors affecting its magnitude. In addition, the clinical implications of the ABC phenomenon on the therapeutic efficacy of PEG-conjugated substances/PEGylated nanocarriers, along with the new approaches that can be applied to manage and/or abrogate the induction of the ABC phenomenon, are also discussed.

Integrity signals

Registry

Crossref · 10.1016/j.jconrel.2013.07.026

Cites

91 of 91 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In preclinical studies, the presence of anti-PEG IgM in animal serum accelerated nanoparticle clearance.

    “In preclinical studies, the presence of anti-PEG IgM in animal serum accelerated nanoparticle clearance and caused a complete loss of the efficacy of mRNA therapeutics217,218.”
  • In preclinical studies, the presence of anti-PEG IgM in animal serum caused a complete loss of the efficacy of mRNA therapeutics.

    “In preclinical studies, the presence of anti-PEG IgM in animal serum accelerated nanoparticle clearance and caused a complete loss of the efficacy of mRNA therapeutics217,218.”
  • PEG-lipids could induce hypersensitivity reactions by stimulating the complement system.

    “Lipid components may activate host immune responses following systemic or local administration; for example, PEG-lipids could induce hypersensitivity reactions by stimulating the complement system127,169.”

    From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [169]

  • Numerous natural and synthetic polymers have been investigated as alternatives to PEG, several of which are under evaluation in clinical trials.

    “To ameliorate safety concerns, numerous natural and synthetic polymers have been investigated as alternatives to PEG, of which several are under evaluation in clinical trials127,169.”

    From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [169]

  • Anti-PEG antibodies could result in fast systemic clearance of subsequently administered PEGylated nanoparticles by accelerated blood clearance.

    “Moreover, anti-PEG antibodies could result in fast systemic clearance of subsequently administered PEGylated nanoparticles by accelerated blood clearance127,169.”

    From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [169]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Abu Lila, A. S., Kiwada, H., & Ishida, T.
Affiliations
Tokushima University (JP)
Corresponding author
Ishida, Tatsuhiro
Venue
Journal of Controlled Release
Publisher
Elsevier BV
Published
2013-11
Volume
172
Issue
1
Pages
38-47
ISSN
0168-3659 (ISSN-L)
OpenAlex
W1987259801
Cited by
721
References
91
Citations by year
2026: 80 · 2025: 73 · 2024: 70 · 2023: 80 · 2022: 76 · 2021: 55 · 2020: 62 · 2019: 46 · 2018: 50 · 2017: 27 · 2016: 38 · 2015: 34 · 2014: 26 · 2013: 3 · 2012: 1
FWCI
2.29
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Controlled Release (publishedVersion)
  • PubMed (publishedVersion)
Funders
Ministry of Education, Culture, Sports, Science and Technology
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
accelerated blood clearance, PEGylation, polyethylene glycol, PEGylated liposomes, PEGylated nanoparticles, immunogenicity, drug clearance, treatment efficacy
MeSH terms
Animals, Complement Activation, Drug Carriers, Humans, Immunoglobulin M, Liposomes, Polyethylene Glycols, Spleen

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review