Highly Stable, Ultrasmall Polymer-Grafted Nanobins (usPGNs) with Stimuli-Responsive Capability
Year: 2018
Type: article
Abstract: Highly stable and stimuli/pH-responsive ultrasmall polymer-grafted nanobins (usPGNs) have been developed by grafting a small amount (10 mol %) of short (4.3 kDa) cholesterol-terminated poly(acrylic acid) (Chol-PAA) into an ultrasmall unilamellar vesicle (uSUV). The usPGNs are stable against fusion and aggregation over several weeks, exhibiting over 10-fold enhanced cargo retention in biologically relevant media at pH 7.4 in comparison with the parent uSUV template. Coarse-grained molecular dynamics (CGMD) simulations confirm that the presence of the cholesterol moiety can greatly stabilize the lipid bilayer. They also show extended PAA chain conformations that can be interpreted as causing repulsion between colloidal particles, thus stabilizing them against fusion. Notably, CGMD predicted a clustering of the Chol-PAA chains on the lipid bilayer under acidic conditions due to intra- and interchain hydrogen bonding, leading to the destabilization of local membrane areas. This explains the experimental observation that usPGNs can be triggered to release a significant amount of cargo upon acidification to pH 5. These developments put the lipid-bilayer-embedded Chol-PAA in stark contrast with traditional poly(acrylic acid) systems where the molar mass ( M n ) of the polymer chains must exceed 16.5 kDa to achieve stimuli-responsive changes in conformation. They also distinguish the small usPGNs from the much-larger polymer-caged nanobin platform where the Chol-PAA chains must be covalently cross-linked to engender stimuli-responsive behaviors.
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: green
Funders: National Science Foundation, U.S. Department of Energy, W. M. Keck Foundation, Chicago Community Trust, 3M, Northwestern University, National Institutes of Health, Office of Science, Robert H. Lurie Comprehensive Cancer Center, Materials Research Science and Engineering Center, Harvard University, National Cancer Institute, National Institute of General Medical Sciences, Division of Materials Research, Division of Engineering Education and Centers, Basic Energy Sciences
Awards: G1164661550, G1404777407, Nanoscale Science & Engineering Center for Integrated Nanopatterning and Detection Technologies, G1675246941, G1908987099, Nucleic Acid-Based Nanoconstructs for the Treatment of Cancer, G2379832748, G317886719, G318734614, G3494156572, G4299555427, G4729179044, Medical Scientist Training Program, Molecular Biophysics Training Program at Northwestern University, G5779363204, G6066762027, Nanomaterials for Cancer Diagnostics and Therapeutics, G7073928473, G7178204, G7998580132, CEMRI: Multifunctional Nanoscale Material Structures, Tumor Targeted Nanobins for the Treatment of Metastatic Breast and Ovarian Cancer, G9000279576, The Robert H. Lurie Comprehensive Cancer Center
OpenAlex ID: W2787045146