TY - JOUR
T1 - Hyaluronan-coated nanoparticles
T2 - The influence of the molecular weight on CD44-hyaluronan interactions and on the immune response
AU - Mizrahy, Shoshy
AU - Raz, Sabina Rebe
AU - Hasgaard, Martin
AU - Liu, Hong
AU - Soffer-Tsur, Neta
AU - Cohen, Keren
AU - Dvash, Ram
AU - Landsman-Milo, Dalit
AU - Bremer, Maria G.E.G.
AU - Moghimi, S. Moein
AU - Peer, Dan
N1 - Funding Information: S.M. thanks TAU Nano Center for Ph.D. fellowship. SMM gratefully acknowledges financial support by the Danish Agency for Science, Technology and Innovation reference 09-065746/DSF. This work was supported in part by grants from the Alon Foundation , the Marie Curie IRG-FP7 of the European Union , Levy Family Trust and Israel Science Foundation (Award # 181/10 ), and the I-core excellence center on human complex diseases to DP.
PY - 2011/12/10
Y1 - 2011/12/10
N2 - Hyaluronan (HA), a naturally occurring glycosaminoglycan, exerts different biological functions depending on its molecular weight ranging from 4000-10M Da. While high Mw HA (HMw-HA) is considered as anti-inflammatory, low Mw HA (LMw-HA) has been reported to activate an innate immune response. In addition, opposing effects on cell proliferation mediated by the HA receptor CD44, have also been reported for high and low Mw HA. We have previously demonstrated that HMw-HA can be covalently attached to the surface of lipid nanoparticles (NPs), endowing the carriers with long circulation and active targeting towards HA-receptors (CD44 and CD168) highly expressed on tumors. Here we present a small library of HA-coated NPs distinguished only by the Mw of their surface anchored HA ranging from 6.4 kDa to 1500 kDa. All types of NPs exerted no effect on macrophages, T cells and ovarian cancer cells proliferation. In addition, no induction of cytokines or complement activation was observed. The affinity towards the CD44 receptor was found to be solely controlled by the Mw of the NPs surface-bound HA, from extremely low binding for LMw-HA to binding with high affinity for HMw-HA. These findings have major implications for the use of HA in nanomedicine as LMw-HA surface modified-NPs could be a viable option for the replacement of polyethylene glycol (PEG) when passive delivery is required, lacking adverse effects such as complement activation and cytokine induction, while HMw-HA-coated NPs could be used for active targeting to CD44 overexpressing tumors and aberrantly activated leukocytes in inflammation.
AB - Hyaluronan (HA), a naturally occurring glycosaminoglycan, exerts different biological functions depending on its molecular weight ranging from 4000-10M Da. While high Mw HA (HMw-HA) is considered as anti-inflammatory, low Mw HA (LMw-HA) has been reported to activate an innate immune response. In addition, opposing effects on cell proliferation mediated by the HA receptor CD44, have also been reported for high and low Mw HA. We have previously demonstrated that HMw-HA can be covalently attached to the surface of lipid nanoparticles (NPs), endowing the carriers with long circulation and active targeting towards HA-receptors (CD44 and CD168) highly expressed on tumors. Here we present a small library of HA-coated NPs distinguished only by the Mw of their surface anchored HA ranging from 6.4 kDa to 1500 kDa. All types of NPs exerted no effect on macrophages, T cells and ovarian cancer cells proliferation. In addition, no induction of cytokines or complement activation was observed. The affinity towards the CD44 receptor was found to be solely controlled by the Mw of the NPs surface-bound HA, from extremely low binding for LMw-HA to binding with high affinity for HMw-HA. These findings have major implications for the use of HA in nanomedicine as LMw-HA surface modified-NPs could be a viable option for the replacement of polyethylene glycol (PEG) when passive delivery is required, lacking adverse effects such as complement activation and cytokine induction, while HMw-HA-coated NPs could be used for active targeting to CD44 overexpressing tumors and aberrantly activated leukocytes in inflammation.
KW - CD44
KW - Complement activation
KW - Hyaluronan
KW - Nanomedicine
KW - Nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=81255127530&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jconrel.2011.06.031
DO - https://doi.org/10.1016/j.jconrel.2011.06.031
M3 - مقالة
SN - 0168-3659
VL - 156
SP - 231
EP - 238
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -
