pH and Amphiphilic Structure Direct Supramolecular Behavior in Biofunctional Assemblies

Moyer, Tyson J.; Finbloom, Joel A.; Chen, Feng; Toft, Daniel J.; Cryns, Vincent L.; Stupp, Samuel I.

doi:10.1021/ja5042429

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

Journal Article · Mon Oct 13 00:00:00 EDT 2014 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/ja5042429· OSTI ID:1165620

Moyer, Tyson J. ^[1]; Finbloom, Joel A. ^[2]; Chen, Feng ^[3]; Toft, Daniel J. ^[4]; Cryns, Vincent L. ^[5]; Stupp, Samuel I. ^[6]

Northwestern Univ., Chicago, IL (United States). Inst. for BioNanotechnology in Medicine, Dept. of Materials Science and Engineering
Northwestern Univ., Chicago, IL (United States). Inst. for BioNanotechnology in Medicine; Northwestern Univ., Evanston, IL (United States). Dept. of Chemistry
Northwestern Univ., Chicago, IL (United States). Inst. for BioNanotechnology in Medicine; Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine, Dept. of Medicine
Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine, Dept. of Medicine
Univ. of Wisconsin, Madison, WI (United States). School of Medicine and Public Health, Carbone Cancer Center and Dept. of Medicine
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

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 H₆ 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 H₆-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 pharmacologic properties of nanomedicines.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC); National Institutes of Health (NIH); Department of Defense (DoD)

Grant/Contract Number:: AC02-06CH11357; 5U54CA151880-03; 5R01DE015920-09; W81XWH-10-1-0503

OSTI ID:: 1165620

Journal Information:: Journal of the American Chemical Society, Vol. 136, Issue 42; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 137 works

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