Complement activation cascade triggered by PEG-PL engineered nanomedicines and carbon nanotubes: The challenges ahead

S. M. Moghimi; A. J. Andersen; S. H. Hashemi; B. Lettiero; D. Ahmadvand; A. C. Hunter; T. L. Andresen; I. Hamad; J. Szebeni

doi:10.1016/j.jconrel.2010.04.003

Complement activation cascade triggered by PEG-PL engineered nanomedicines and carbon nanotubes: The challenges ahead

S. M. Moghimi, A. J. Andersen, S. H. Hashemi, B. Lettiero, D. Ahmadvand, A. C. Hunter, T. L. Andresen, I. Hamad, J. Szebeni

Research output: Contribution to journal › Article › peer-review

164 Scopus citations

Abstract

Since their introduction, poly(ethylene glycol)-phospholipid (PEG-PL) conjugates have found many applications in design and engineering of nanosized delivery systems for controlled delivery of pharmaceuticals especially to non-macrophage targets. However, there are reports of idiosyncratic reactions to certain PEG-PL engineered nanomedicines in both experimental animals and man. These reactions are classified as pseudoallergy and may be associated with cardiopulmonary disturbance and other related symptoms of anaphylaxis. Recent studies suggest that complement activation may be a contributing, but not a rate limiting factor, in eliciting hypersensitivity reactions to such nanomedicines in sensitive individuals. This is rather surprising since PEGylated structures are generally assumed to suppress protein adsorption and blood opsonization events including complement. Here, we examine the molecular basis of complement activation by PEG-PL engineered nanomedicines and carbon nanotubes and discuss the challenges ahead.

Original language	English (US)
Pages (from-to)	175-181
Number of pages	7
Journal	Journal of Controlled Release
Volume	146
Issue number	2
DOIs	https://doi.org/10.1016/j.jconrel.2010.04.003
State	Published - Sep 2010

Keywords

Carbon nanotube
Complement activation
Liposome
Micelle
Poly(ethylene glycol)
Pseudoallergy

ASJC Scopus subject areas

Pharmaceutical Science

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10.1016/j.jconrel.2010.04.003

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title = "Complement activation cascade triggered by PEG-PL engineered nanomedicines and carbon nanotubes: The challenges ahead",

abstract = "Since their introduction, poly(ethylene glycol)-phospholipid (PEG-PL) conjugates have found many applications in design and engineering of nanosized delivery systems for controlled delivery of pharmaceuticals especially to non-macrophage targets. However, there are reports of idiosyncratic reactions to certain PEG-PL engineered nanomedicines in both experimental animals and man. These reactions are classified as pseudoallergy and may be associated with cardiopulmonary disturbance and other related symptoms of anaphylaxis. Recent studies suggest that complement activation may be a contributing, but not a rate limiting factor, in eliciting hypersensitivity reactions to such nanomedicines in sensitive individuals. This is rather surprising since PEGylated structures are generally assumed to suppress protein adsorption and blood opsonization events including complement. Here, we examine the molecular basis of complement activation by PEG-PL engineered nanomedicines and carbon nanotubes and discuss the challenges ahead.",

keywords = "Carbon nanotube, Complement activation, Liposome, Micelle, Poly(ethylene glycol), Pseudoallergy",

author = "Moghimi, {S. M.} and Andersen, {A. J.} and Hashemi, {S. H.} and B. Lettiero and D. Ahmadvand and Hunter, {A. C.} and Andresen, {T. L.} and I. Hamad and J. Szebeni",

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AU - Moghimi, S. M.

AU - Andersen, A. J.

AU - Hashemi, S. H.

AU - Lettiero, B.

AU - Ahmadvand, D.

AU - Hunter, A. C.

AU - Andresen, T. L.

AU - Hamad, I.

AU - Szebeni, J.

PY - 2010/9

Y1 - 2010/9

N2 - Since their introduction, poly(ethylene glycol)-phospholipid (PEG-PL) conjugates have found many applications in design and engineering of nanosized delivery systems for controlled delivery of pharmaceuticals especially to non-macrophage targets. However, there are reports of idiosyncratic reactions to certain PEG-PL engineered nanomedicines in both experimental animals and man. These reactions are classified as pseudoallergy and may be associated with cardiopulmonary disturbance and other related symptoms of anaphylaxis. Recent studies suggest that complement activation may be a contributing, but not a rate limiting factor, in eliciting hypersensitivity reactions to such nanomedicines in sensitive individuals. This is rather surprising since PEGylated structures are generally assumed to suppress protein adsorption and blood opsonization events including complement. Here, we examine the molecular basis of complement activation by PEG-PL engineered nanomedicines and carbon nanotubes and discuss the challenges ahead.

AB - Since their introduction, poly(ethylene glycol)-phospholipid (PEG-PL) conjugates have found many applications in design and engineering of nanosized delivery systems for controlled delivery of pharmaceuticals especially to non-macrophage targets. However, there are reports of idiosyncratic reactions to certain PEG-PL engineered nanomedicines in both experimental animals and man. These reactions are classified as pseudoallergy and may be associated with cardiopulmonary disturbance and other related symptoms of anaphylaxis. Recent studies suggest that complement activation may be a contributing, but not a rate limiting factor, in eliciting hypersensitivity reactions to such nanomedicines in sensitive individuals. This is rather surprising since PEGylated structures are generally assumed to suppress protein adsorption and blood opsonization events including complement. Here, we examine the molecular basis of complement activation by PEG-PL engineered nanomedicines and carbon nanotubes and discuss the challenges ahead.

KW - Carbon nanotube

KW - Complement activation

KW - Liposome

KW - Micelle

KW - Poly(ethylene glycol)

KW - Pseudoallergy

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Complement activation cascade triggered by PEG-PL engineered nanomedicines and carbon nanotubes: The challenges ahead

Abstract

Keywords

ASJC Scopus subject areas

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