TY - JOUR
T1 - Macromolecular pHPMA-Based Nanoparticles with Cholesterol for Solid Tumor Targeting
T2 - Behavior in HSA Protein Environment
AU - Zhang, Xiaohan
AU - Niebuur, Bart Jan
AU - Chytil, Petr
AU - Etrych, Tomas
AU - Filippov, Sergey K.
AU - Kikhney, Alexey
AU - Wieland, D. C.Florian
AU - Svergun, Dmitri I.
AU - Papadakis, Christine M.
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/2/12
Y1 - 2018/2/12
N2 - Nanoparticles (NPs) that form by self-assembly of amphiphilic poly(N-(2-hydroxypropyl)-methacrylamide) (pHPMA) copolymers bearing cholesterol side groups are potential drug carriers for solid tumor treatment. Here, we investigate their behavior in solutions of human serum albumin (HSA) in phosphate buffered saline. Mixed solutions of NPs, from polymer conjugates with or without the anticancer drug doxorubicin (Dox) bound to them, and HSA at concentrations up to the physiological value are characterized by synchrotron small-angle X-ray scattering and isothermal titration calorimetry. When Dox is absent, a small amount of HSA molecules bind to the cholesterol groups that form the core of the NPs by diffusing through the loose pHPMA shell or get caught in meshes formed by the pHPMA chains. These interactions are strongly hindered by the presence of Dox, which is distributed in the pHPMA shell, meaning that the delivery of Dox by the NPs in the human body is not affected by the presence of HSA.
AB - Nanoparticles (NPs) that form by self-assembly of amphiphilic poly(N-(2-hydroxypropyl)-methacrylamide) (pHPMA) copolymers bearing cholesterol side groups are potential drug carriers for solid tumor treatment. Here, we investigate their behavior in solutions of human serum albumin (HSA) in phosphate buffered saline. Mixed solutions of NPs, from polymer conjugates with or without the anticancer drug doxorubicin (Dox) bound to them, and HSA at concentrations up to the physiological value are characterized by synchrotron small-angle X-ray scattering and isothermal titration calorimetry. When Dox is absent, a small amount of HSA molecules bind to the cholesterol groups that form the core of the NPs by diffusing through the loose pHPMA shell or get caught in meshes formed by the pHPMA chains. These interactions are strongly hindered by the presence of Dox, which is distributed in the pHPMA shell, meaning that the delivery of Dox by the NPs in the human body is not affected by the presence of HSA.
UR - http://www.scopus.com/inward/record.url?scp=85041910369&partnerID=8YFLogxK
U2 - 10.1021/acs.biomac.7b01579
DO - 10.1021/acs.biomac.7b01579
M3 - Article
C2 - 29381335
AN - SCOPUS:85041910369
SN - 1525-7797
VL - 19
SP - 470
EP - 480
JO - Biomacromolecules
JF - Biomacromolecules
IS - 2
ER -