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Int J Pharm. 2018 Jan 30;536(1):434-439. doi: 10.1016/j.ijpharm.2017.11.072. Epub 2017 Dec 5.

Impact of the surface charge of polydiacetylene micelles on their interaction with human innate immune protein C1q and the complement system.

Author information

1
Univ. Grenoble Alpes, CEA, CNRS, IBS, F-38000 Grenoble, France.
2
Service de Chimie Bioorganique et de Marquage (SCBM), CEA, Université Paris-Saclay, 91191 Gif-sur-Yvette, France.
3
Service de Chimie Bioorganique et de Marquage (SCBM), CEA, Université Paris-Saclay, 91191 Gif-sur-Yvette, France. Electronic address: eric.doris@cea.fr.
4
Univ. Grenoble Alpes, CEA, CNRS, IBS, F-38000 Grenoble, France. Electronic address: wai-li.ling@ibs.fr.

Abstract

Polydiacetylene (pDA) micelles have been demonstrated to be effective drug carriers for cancer therapy in mouse model. However, little is known about their interaction with the human complement system, which constitutes an important part of the innate immune system and can cause severe hypersensitivity reactions. Herein, we investigate the influence of micelle surface charge on the binding of complement protein C1q, the target recognition unit that activates the classical complement pathway and performs a range of other important physiological functions. Besides the classical pathway, we also investigate the surface charge effect on complement activities through the other activation pathways, namely, the MBL-dependent lectin pathway and the alternative pathway. We synthesized three samples of pDA micelles bearing neutral, anionic, and cationic surface charge motifs, respectively. Surface plasmon resonance showed that none of these micelles interacted with C1q. Results from serum complement activation assays indicated that all micelles were inert to complement, except for the anionic pDA micelles, which activated the alternative pathway.

KEYWORDS:

C1q; Complement; Innate immune system; Polydiacetylene micelle; Surface charge

PMID:
29208412
DOI:
10.1016/j.ijpharm.2017.11.072
[Indexed for MEDLINE]

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