TY - JOUR
T1 - Structural profiling and biological performance of phospholipid-hyaluronan functionalized single-walled carbon nanotubes
AU - Dvash, Ram
AU - Khatchatouriants, Artium
AU - Solmesky, Leonardo J.
AU - Wibroe, Peter P.
AU - Weil, Miguel
AU - Moghimi, S. Moein
AU - Peer, Dan
PY - 2013
Y1 - 2013
N2 - In spite of significant insolubility and toxicity, carbon nanotubes (CNTs) erupt into the biomedical research, and create an increasing interest in the field of nanomedicine. Single-walled CNTs (SWCNTs) are highly hy-drophobic and have been shown to be toxic while systemically administrated. Thus, SWCNTs have to be functionalized to render water solubility and biocompatibility. Herein, we introduce a method for functionalizing SWCNT using phospholipids (PL) conjugated to hyaluronan (HA), a hydrophilic glycosaminoglycan, with known receptors on many types of cancer and immune cells. This functionalization allowed for CNT solubi-lization, endowed the particles with stealth properties evading the immune system, and reduced immune and mitochondrial toxicity both in vitro and in vivo. The CNT-PL-HA internalized into macrophages and showed low cytotoxicity. In addition, CNT-PL-HA did not induce an inflammatory response in macrophages as evidenced by the cytokine profiling and the use of image-based high-content analysis approach in contrast to non-modified CNTs. In addition, systemic administration of CNT-PL-HA into healthy C57BL/6 mice did not alter the total number of leukocytes nor increased liver enzyme release as opposed to CNTs. Taken together, these results suggest an immune protective mechanism by the PL-HA coating that could provide future therapeutic benefit.
AB - In spite of significant insolubility and toxicity, carbon nanotubes (CNTs) erupt into the biomedical research, and create an increasing interest in the field of nanomedicine. Single-walled CNTs (SWCNTs) are highly hy-drophobic and have been shown to be toxic while systemically administrated. Thus, SWCNTs have to be functionalized to render water solubility and biocompatibility. Herein, we introduce a method for functionalizing SWCNT using phospholipids (PL) conjugated to hyaluronan (HA), a hydrophilic glycosaminoglycan, with known receptors on many types of cancer and immune cells. This functionalization allowed for CNT solubi-lization, endowed the particles with stealth properties evading the immune system, and reduced immune and mitochondrial toxicity both in vitro and in vivo. The CNT-PL-HA internalized into macrophages and showed low cytotoxicity. In addition, CNT-PL-HA did not induce an inflammatory response in macrophages as evidenced by the cytokine profiling and the use of image-based high-content analysis approach in contrast to non-modified CNTs. In addition, systemic administration of CNT-PL-HA into healthy C57BL/6 mice did not alter the total number of leukocytes nor increased liver enzyme release as opposed to CNTs. Taken together, these results suggest an immune protective mechanism by the PL-HA coating that could provide future therapeutic benefit.
KW - Carbon nanotubes
KW - Cytotoxicity
KW - High-content analysis
KW - Hyaluronan
KW - Immune response
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U2 - 10.1016/j.jconrel.2013.05.042
DO - 10.1016/j.jconrel.2013.05.042
M3 - Article
C2 - 23764531
AN - SCOPUS:84879487807
VL - 170
SP - 295
EP - 305
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 2
ER -