Complement Deposition on Nanoparticles Can Modulate Immune Responses by Macrophage, B and T Cells.
Nanoparticles are attractive drug delivery vehicles for targeted organ-specific as well as systemic therapy. However, their interaction with the immune system offers an intriguing challenge to the success of nanotherapeutics in vivo. Recently, we showed that pristine and derivatised carbon nanotubes (CNT) can activate complement mainly via the classical pathway leading to enhanced uptake by phagocytic cells, and transcriptional down-regulation of pro-inflammatory cytokines. Here, we report the interaction of complement-activating CC-CNT and RNA-CNT, and non-complement-activating gold-nickel (Au-Ni) nanowires with cell lines representing macrophage, B and T cells. Complement deposition considerably enhanced uptake of CNTs by immune cells known to overexpress complement receptors. Real-Time qPCR and multiplex array analyses showed complement-dependent down-regulation of TNF-α and IL-1β and up-regulation of IL-12 by CMC- and RNA-CNTs, in addition to revealing IL-10 as a crucial regulator during nanoparticle-immune cell interaction. It appears that complement system can recognize molecular patterns differentially displayed by nanoparticles and thus, modulate subsequent processing of nanoparticles by antigen capturing and antigen presenting cells, which can shape innate and adaptive immune axes.
Kirsten M
KM
Pondman
Anthony G
AG
Tsolaki
Basudev
B
Paudyal
Mohamed H
MH
Shamji
Amy
A
Switzer
Ansar A
AA
Pathan
Suhair M
SM
Abozaid
Bennie
B
Ten Haken
Gudrun
G
Stenbeck
Robert B
RB
Sim
Uday
U
Kishore
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000633:toxicity; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008422:Materials Testing; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D020099:Coated Materials, Biocompatible; D016207:Cytokines; D037742:Nanotubes, Carbon