PH and amphiphilic structure direct supramolecular behavior in biofunctional assemblies

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

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

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). 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. Our findings also suggest that these supramolecular events can be tuned by molecular design to improve the pharmacologic properties of nanomedicines.

Original languageEnglish
Pages (from-to)14746-14752
Number of pages7
JournalJournal of the American Chemical Society
Volume136
Issue number42
DOIs
Publication statusPublished - Oct 22 2014

Fingerprint

Nanofibers
Amphiphiles
Peptides
Nanostructures
Micelles
Tumors
Camptothecin
Encapsulation
Histidine
Nanomedicine
Medical nanotechnology
Tumor Microenvironment
Chemotherapy
Protonation
Self assembly
Neoplasms
Drug Therapy
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

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.

In: Journal of the American Chemical Society, Vol. 136, No. 42, 22.10.2014, p. 14746-14752.

Research output: Contribution to journalArticle

Moyer, Tyson J. ; Finbloom, Joel A. ; Chen, Feng ; Toft, Daniel J. ; Cryns, Vincent L. ; Stupp, Samuel I. / PH and amphiphilic structure direct supramolecular behavior in biofunctional assemblies. In: Journal of the American Chemical Society. 2014 ; Vol. 136, No. 42. pp. 14746-14752.
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