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

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). 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 ofmore » 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:
Research Org.:
Argonne National Laboratory (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)
OSTI Identifier:
1165620
Grant/Contract Number:  
AC02-06CH11357; 5U54CA151880-03; 5R01DE015920-09; W81XWH-10-1-0503
Resource Type:
Journal Article: 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)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 60 APPLIED LIFE SCIENCES

Citation Formats

Moyer, Tyson J., Finbloom, Joel A., Chen, Feng, Toft, Daniel J., Cryns, Vincent L., and Stupp, Samuel I. pH and Amphiphilic Structure Direct Supramolecular Behavior in Biofunctional Assemblies. United States: N. p., 2014. Web. doi:10.1021/ja5042429.
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. United States. https://doi.org/10.1021/ja5042429
Moyer, Tyson J., Finbloom, Joel A., Chen, Feng, Toft, Daniel J., Cryns, Vincent L., and Stupp, Samuel I. 2014. "pH and Amphiphilic Structure Direct Supramolecular Behavior in Biofunctional Assemblies". United States. https://doi.org/10.1021/ja5042429. https://www.osti.gov/servlets/purl/1165620.
@article{osti_1165620,
title = {pH and Amphiphilic Structure Direct Supramolecular Behavior in Biofunctional Assemblies},
author = {Moyer, Tyson J. and Finbloom, Joel A. and Chen, Feng and Toft, Daniel J. and Cryns, Vincent L. and Stupp, Samuel I.},
abstractNote = {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.},
doi = {10.1021/ja5042429},
url = {https://www.osti.gov/biblio/1165620}, journal = {Journal of the American Chemical Society},
issn = {0002-7863},
number = 42,
volume = 136,
place = {United States},
year = {Mon Oct 13 00:00:00 EDT 2014},
month = {Mon Oct 13 00:00:00 EDT 2014}
}

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Works referenced in this record:

Nanocarriers as an emerging platform for cancer therapy
journal, December 2007


Nanoparticle therapeutics: an emerging treatment modality for cancer
journal, September 2008


Shape effects of filaments versus spherical particles in flow and drug delivery
journal, March 2007


Micelles of Different Morphologies—Advantages of Worm-like Filomicelles of PEO-PCL in Paclitaxel Delivery
journal, June 2007


Flexible Filaments for in Vivo Imaging and Delivery: Persistent Circulation of Filomicelles Opens the Dosage Window for Sustained Tumor Shrinkage
journal, March 2009


The effect of particle design on cellular internalization pathways
journal, August 2008


Drug Resistance and Cellular Adaptation to Tumor Acidic pH Microenvironment
journal, October 2011


Polymeric anticancer drugs with pH-controlled activation
journal, June 2004


N-Boc-Histidine-Capped PLGA-PEG-PLGA as a Smart Polymer for Drug Delivery Sensitive to Tumor Extracellular pH
journal, June 2010


In vivo tumor diagnosis and photodynamic therapy via tumoral pH-responsive polymeric micelles
journal, January 2010


Doxorubicin loaded pH-sensitive micelle targeting acidic extracellular pH of human ovarian A2780 tumor in mice
journal, August 2005


Tumor pH-responsive flower-like micelles of poly(l-lactic acid)-b-poly(ethylene glycol)-b-poly(l-histidine)
journal, October 2007


Functional Supramolecular Polymers
journal, February 2012


Self-assembly of peptide amphiphiles: From molecules to nanostructures to biomaterials
journal, January 2010


Nanostructure-templated control of drug release from peptide amphiphile nanofiber gels
journal, January 2012


Fine-Tuning the pH Trigger of Self-Assembly
journal, February 2012


Structural properties of soluble peptide amphiphile micelles
journal, January 2011


Self-assembly and applications of biomimetic and bioactive peptide-amphiphiles
journal, January 2006


Peptide-amphiphile nanofibers: A versatile scaffold for the preparation of self-assembling materials
journal, April 2002


Molecular Simulation Study of Peptide Amphiphile Self-Assembly
journal, February 2008


pH-responsive branched peptide amphiphile hydrogel designed for applications in regenerative medicine with potential as injectable tissue scaffolds
journal, January 2012


Induction of Cancer Cell Death by Self-assembling Nanostructures Incorporating a Cytotoxic Peptide
journal, March 2010


Antitumor Activity of Peptide Amphiphile Nanofiber-Encapsulated Camptothecin
journal, October 2011


Switching of self-assembly in a peptide nanostructure with a specific enzyme
journal, January 2011


Responsive Vesicles from Dynamic Covalent Surfactants
journal, March 2011


Light-induced self-assembly of nanofibers inside liposomes
journal, January 2008


Light-Triggered Bioactivity in Three Dimensions
journal, July 2009


Prediction of “Aggregation-prone” and “Aggregation-susceptible” Regions in Proteins Associated with Neurodegenerative Diseases
journal, July 2005


Self-Assembly of Peptide−Amphiphile Nanofibers:  The Roles of Hydrogen Bonding and Amphiphilic Packing
journal, June 2006


Tuning Supramolecular Rigidity of Peptide Fibers through Molecular Structure
journal, May 2010


Cationic Nanoparticles Have Superior Transvascular Flux into Solid Tumors: Insights from a Mathematical Model
journal, August 2012


Self-assembly of peptide amphiphiles: From molecules to nanostructures to biomaterials
journal, January 2010


N-Boc-Histidine-Capped PLGA-PEG-PLGA as a Smart Polymer for Drug Delivery Sensitive to Tumor Extracellular pH
journal, June 2010


Cationic Nanoparticles Have Superior Transvascular Flux into Solid Tumors: Insights from a Mathematical Model
journal, August 2012


Prediction of “Aggregation-prone” and “Aggregation-susceptible” Regions in Proteins Associated with Neurodegenerative Diseases
journal, July 2005


Self-Assembly of Peptide−Amphiphile Nanofibers:  The Roles of Hydrogen Bonding and Amphiphilic Packing
journal, June 2006


Fine-Tuning the pH Trigger of Self-Assembly
journal, February 2012


Tuning Supramolecular Rigidity of Peptide Fibers through Molecular Structure
journal, May 2010


Molecular Simulation Study of Peptide Amphiphile Self-Assembly
journal, February 2008


Antitumor Activity of Peptide Amphiphile Nanofiber-Encapsulated Camptothecin
journal, October 2011


Nanocarriers as an emerging platform for cancer therapy
journal, December 2007


Shape effects of filaments versus spherical particles in flow and drug delivery
journal, March 2007


Light-induced self-assembly of nanofibers inside liposomes
journal, January 2008


Nanostructure-templated control of drug release from peptide amphiphile nanofiber gels
journal, January 2012


The effect of particle design on cellular internalization pathways
journal, August 2008


Functional Supramolecular Polymers
journal, February 2012


Works referencing / citing this record:

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journal, January 2019


A review on virus protein self-assembly
journal, November 2019


A minimal length rigid helical peptide motif allows rational design of modular surfactants
journal, January 2017


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journal, February 2017


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journal, January 2019


Self-assembly of mitochondria-specific peptide amphiphiles amplifying lung cancer cell death through targeting the VDAC1–hexokinase-II complex
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journal, January 2020


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journal, January 2019


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journal, October 2019


Secondary Structure-Driven Hydrogelation Using Foldable Telechelic Polymer-Peptide Conjugates
journal, July 2018


Supramolecular Nanofibers of Curcumin for Highly Amplified Radiosensitization of Colorectal Cancers to Ionizing Radiation
journal, January 2018


Peptide supramolecular materials for therapeutics
journal, January 2018


Transformable Peptide Nanocarriers for Expeditious Drug Release and Effective Cancer Therapy via Cancer-Associated Fibroblast Activation
journal, August 2015


MMP-2-Controlled Transforming Micelles for Heterogeneic Targeting and Programmable Cancer Therapy
journal, January 2019