TY - JOUR
T1 - Cyclic Peptide–Polymer Nanotubes as Efficient and Highly Potent Drug Delivery Systems for Organometallic Anticancer Complexes
AU - Larnaudie, Sophie C.
AU - Brendel, Johannes C.
AU - Romero-Canelón, Isolda
AU - Sanchez-Cano, Carlos
AU - Catrouillet, Sylvain
AU - Sanchis, Joaquin
AU - Coverdale, James P. C.
AU - Song, Ji-Inn
AU - Habtemariam, Abraha
AU - Sadler, Peter J.
AU - Jolliffe, Katrina A.
AU - Perrier, Sébastien
PY - 2018/1/8
Y1 - 2018/1/8
N2 - Functional drug carrier systems have potential for increasing solubility and potency of drugs while reducing side effects. Complex polymeric materials, particularly anisotropic structures, are especially attractive due to their long circulation times. Here, we have conjugated cyclic peptides to the biocompatible polymer poly(2-hydroxypropyl methacrylamide) (pHPMA). The resulting conjugates were functionalized with organoiridium anticancer complexes. Small angle neutron scattering and static light scattering confirmed their self-assembly and elongated cylindrical shape. Drug-loaded nanotubes exhibited more potent antiproliferative activity toward human cancer cells than either free drug or the drug-loaded polymers, while the nanotubes themselves were nontoxic. Cellular accumulation studies revealed that the increased potency of the conjugate appears to be related to a more efficient mode of action rather than a higher cellular accumulation of iridium.
AB - Functional drug carrier systems have potential for increasing solubility and potency of drugs while reducing side effects. Complex polymeric materials, particularly anisotropic structures, are especially attractive due to their long circulation times. Here, we have conjugated cyclic peptides to the biocompatible polymer poly(2-hydroxypropyl methacrylamide) (pHPMA). The resulting conjugates were functionalized with organoiridium anticancer complexes. Small angle neutron scattering and static light scattering confirmed their self-assembly and elongated cylindrical shape. Drug-loaded nanotubes exhibited more potent antiproliferative activity toward human cancer cells than either free drug or the drug-loaded polymers, while the nanotubes themselves were nontoxic. Cellular accumulation studies revealed that the increased potency of the conjugate appears to be related to a more efficient mode of action rather than a higher cellular accumulation of iridium.
U2 - 10.1021/acs.biomac.7b01491
DO - 10.1021/acs.biomac.7b01491
M3 - Article
SN - 1525-7797
VL - 19
SP - 239
EP - 247
JO - Biomacromolecules
JF - Biomacromolecules
IS - 1
ER -