TY - JOUR
T1 - Dual responsive PMEEECL-PAE block copolymers
T2 - A computational self-assembly and doxorubicin uptake study
AU - Koochaki, Amin
AU - Moghbeli, Mohammad Reza
AU - Nikkhah, Sousa Javan
AU - Ianiro, Alessandro
AU - Tuinier, Remco
N1 - Publisher Copyright:
© 2020 The Royal Society of Chemistry.
PY - 2020
Y1 - 2020
N2 - The self-assembly behaviour of dual-responsive block copolymers and their ability to solubilize the anticancer drug doxorubicin (DOX) has been investigated using all-atom molecular dynamics (MD) simulations, MARTINI coarse-grained (CG) force field simulation and Scheutjens-Fleer self-consistent field (SCF) computations. These diblock copolymers, composed of poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ϵ-caprolactone} (PMEEECL) and poly(β-amino ester) (PAE) are dual-responsive: the PMEEECL block is thermoresponsive (becomes insoluble above a certain temperature), while the PAE block is pH-responsive (becomes soluble below a certain pH). Three MEEECL20-AEM compositions with M = 5, 10, and 15, have been studied. All-atom MD simulations have been performed to calculate the coil-to-globule transition temperature (Tcg) of these copolymers and finding appropriate CG mapping for both PMEEECL-PAE and DOX. The output of the MARTINI CG simulations is in agreement with SCF predictions. The results show that DOX is solubilized with high efficiency (75-80%) at different concentrations inside the PMEEECL-PAE micelles, although, interestingly, the loading efficiency is reduced by increasing the drug concentration. The non-bonded interaction energy and the RDF between DOX and water beads confirm this result. Finally, MD simulations and SCF computations reveal that the responsive behaviour of PMEEECL-PAE self-assembled structures take place at temperature and pH ranges appropriate for drug delivery.
AB - The self-assembly behaviour of dual-responsive block copolymers and their ability to solubilize the anticancer drug doxorubicin (DOX) has been investigated using all-atom molecular dynamics (MD) simulations, MARTINI coarse-grained (CG) force field simulation and Scheutjens-Fleer self-consistent field (SCF) computations. These diblock copolymers, composed of poly{γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ϵ-caprolactone} (PMEEECL) and poly(β-amino ester) (PAE) are dual-responsive: the PMEEECL block is thermoresponsive (becomes insoluble above a certain temperature), while the PAE block is pH-responsive (becomes soluble below a certain pH). Three MEEECL20-AEM compositions with M = 5, 10, and 15, have been studied. All-atom MD simulations have been performed to calculate the coil-to-globule transition temperature (Tcg) of these copolymers and finding appropriate CG mapping for both PMEEECL-PAE and DOX. The output of the MARTINI CG simulations is in agreement with SCF predictions. The results show that DOX is solubilized with high efficiency (75-80%) at different concentrations inside the PMEEECL-PAE micelles, although, interestingly, the loading efficiency is reduced by increasing the drug concentration. The non-bonded interaction energy and the RDF between DOX and water beads confirm this result. Finally, MD simulations and SCF computations reveal that the responsive behaviour of PMEEECL-PAE self-assembled structures take place at temperature and pH ranges appropriate for drug delivery.
UR - http://www.scopus.com/inward/record.url?scp=85078541866&partnerID=8YFLogxK
U2 - 10.1039/c9ra09066e
DO - 10.1039/c9ra09066e
M3 - Article
AN - SCOPUS:85078541866
SN - 2046-2069
VL - 10
SP - 3233
EP - 3245
JO - RSC Advances
JF - RSC Advances
IS - 6
ER -