pH-Responsive Nano-Self-Assemblies of the Anticancer Drug 2-Hydroxyoleic Acid

TY - JOUR

T1 - pH-Responsive Nano-Self-Assemblies of the Anticancer Drug 2-Hydroxyoleic Acid

AU - Prajapati, Rama

AU - Gontsarik, Mark

AU - Yaghmur, Anan

AU - Salentinig, Stefan

PY - 2019/6/18

Y1 - 2019/6/18

N2 - pH-responsive lipid nanocarriers have the potential to selectively target the acidic extracellular pH environment of cancer tissues and may further improve the efficacy of chemotherapeutics by minimizing their toxic side-effects. Here, we present the design and characterization of pH-sensitive nano-self-assemblies of the poorly water-soluble anticancer drug 2-hydroxyoleic acid (2OHOA) with glycerol monooleate (GMO). pH-triggered nanostructural transformations from 2OHOA/GMO nanoparticles with an internal inverse hexagonal structure (hexosomes) at pH around 2.0-3.0, via nanocarriers with an internal inverse bicontinuous cubic structure (cubosomes) at pH 2.0-4.5, to vesicles at pH 4.5-7.4 were observed with synchrotron small-angle X-ray scattering, and cryogenic transmission electron microscopy. ζ-potential measurements highlight that the pH-driven deprotonation of the carboxylic group of 2OHOA, and the resulting charge-repulsions at the lipid-water interface account for these nanostructural alterations. The study provides detailed insight into the pH-dependent self-assembly of 2OHOA with GMO in excess buffer at physiologically relevant pH values, and discusses the effects of pH alterations on modulating their nanostructure. The results may guide the further development of pH-responsive anticancer nanocarriers for the targeted delivery of chemotherapeutics to the local microenvironment of tumor cells.

AB - pH-responsive lipid nanocarriers have the potential to selectively target the acidic extracellular pH environment of cancer tissues and may further improve the efficacy of chemotherapeutics by minimizing their toxic side-effects. Here, we present the design and characterization of pH-sensitive nano-self-assemblies of the poorly water-soluble anticancer drug 2-hydroxyoleic acid (2OHOA) with glycerol monooleate (GMO). pH-triggered nanostructural transformations from 2OHOA/GMO nanoparticles with an internal inverse hexagonal structure (hexosomes) at pH around 2.0-3.0, via nanocarriers with an internal inverse bicontinuous cubic structure (cubosomes) at pH 2.0-4.5, to vesicles at pH 4.5-7.4 were observed with synchrotron small-angle X-ray scattering, and cryogenic transmission electron microscopy. ζ-potential measurements highlight that the pH-driven deprotonation of the carboxylic group of 2OHOA, and the resulting charge-repulsions at the lipid-water interface account for these nanostructural alterations. The study provides detailed insight into the pH-dependent self-assembly of 2OHOA with GMO in excess buffer at physiologically relevant pH values, and discusses the effects of pH alterations on modulating their nanostructure. The results may guide the further development of pH-responsive anticancer nanocarriers for the targeted delivery of chemotherapeutics to the local microenvironment of tumor cells.

U2 - 10.1021/acs.langmuir.9b00838

DO - 10.1021/acs.langmuir.9b00838

M3 - Journal article

C2 - 31150248

SN - 0743-7463

VL - 35

SP - 7954

EP - 7961

JO - Langmuir

JF - Langmuir

IS - 24

ER -