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This content will become publicly available on October 13, 2014

Title: pH and Amphiphilic Structure Direct Supramolecular Behavior in Biofunctional Assemblies

Supramolecular self-assembly offers promising new ways to control nanostructure morphology and respond to external stimuli. A pH-sensitive self-assembled system was developed to both control nanostructure shape and respond to the acidic microenvironment of tumors using self-assembling peptide amphiphiles (PAs). Here, by incorporating an oligo-histidine H 6 sequence, we developed two PAs that self-assembled into distinct morphologies on the nanoscale, either as nanofibers or spherical micelles, based on the incorporation of the aliphatic tail on the N-terminus or near the C-terminus, respectively. Both cylinder and sphere-forming PAs demonstrated reversible disassembly between pH 6.0 and 6.5 upon protonation of the histidine residues in acidic solutions. These PAs were then characterized and assessed for their potential to encapsulate hydrophobic chemotherapies. The H 6-based nanofiber assemblies encapsulated camptothecin (CPT) with up to 60% efficiency, a 7-fold increase in CPT encapsulation relative to spherical micelles. Additionally, pH-sensitive nanofibers showed improved tumor accumulation over both spherical micelles and nanofibers that did not change morphologies in acidic environments. We have demonstrated that the morphological transitions upon changes in pH of supramolecular nanostructures affect drug encapsulation and tumor accumulation. Lastly, our findings also suggest that these supramolecular events can be tuned by molecular design to improve the pharmacologicmore » properties of nanomedicines.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6]
  1. Northwestern Univ., Chicago, IL (United States). Inst. for BioNanotechnology in Medicine, Dept. of Materials Science and Engineering
  2. Northwestern Univ., Chicago, IL (United States). Inst. for BioNanotechnology in Medicine; Northwestern Univ., Evanston, IL (United States). Dept. of Chemistry
  3. Northwestern Univ., Chicago, IL (United States). Inst. for BioNanotechnology in Medicine; Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine, Dept. of Medicine
  4. Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine, Dept. of Medicine
  5. Univ. of Wisconsin, Madison, WI (United States). School of Medicine and Public Health, Carbone Cancer Center and Dept. of Medicine
  6. Northwestern Univ., Chicago, IL (United States). Inst. for BioNanotechnology in Medicine, Dept. of Materials Science and Engineering; Northwestern Univ., Evanston, IL (United States). Dept. of Chemistry; Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine, Dept. of Medicine
Publication Date:
OSTI Identifier:
1165620
Grant/Contract Number:
AC02-06CH11357; 5U54CA151880-03; 5R01DE015920-09; W81XWH-10-1-0503
Type:
Accepted Manuscript
Journal Name:
Journal of the American Chemical Society
Additional Journal Information:
Journal Volume: 136; Journal Issue: 42; Journal ID: ISSN 0002-7863
Publisher:
American Chemical Society (ACS)
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org:
USDOE Office of Science (SC); National Institutes of Health (NIH); Department of Defense (DoD)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 60 APPLIED LIFE SCIENCES