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 (Mn) 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1133-1139 |
| Number of pages | 7 |
| Journal | Journal of Physical Chemistry Letters |
| Volume | 9 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 1 2018 |
Funding
This work is financially supported by the NIH (NCI CCNE Grant U54CA199091, NCI CCNE Grant C54CA151880, CCNP Grant U01CA151461, and Core Grant P30CA060553 to the Lurie Cancer Center of Northwestern University (NU)). A.I. and G.C.S. were supported as part of the Center for Bio-Inspired Energy Science, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences, under Award #DE-SC0000989-002. A.J.C was a fellow in the Molecular Biophysics Training Program at Northwestern University (NCI Grant T32GM008382). M.M.L. was supported by a Nanoscale Science and Engineering REU Program (NSF award number EEC-0647560) and a 2013−2014 academic year research grant from Northwestern University. J.N.L. additionally acknowledges supports from a 3M Nontenured Faculty Grant. Instruments in the Northwestern University IMSERC and Keck Biophysics facilities were purchased with grants from NSF-NSEC (NSF EEC-0647560), NIH-CCNE, NSF-MRSEC (NSF DMR-1121262), the Keck Foundation, the state of Illinois, and Northwestern University. The cryo-TEM work was carried out at the Structural Biology Facility at Northwestern University, which was partially supported by the R. H. Lurie Comprehensive Cancer Center. The Gatan K2 direct electron detector was purchased with funds provided by the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust.
ASJC Scopus subject areas
- General Materials Science
- Physical and Theoretical Chemistry