Journal of the American Chemical Society
Article
Naneki C. McCallum − Department of Chemistry,
Qing Zhe Ni − Department of Chemistry & Biochemistry,
University of California, San Diego, La Jolla, California 92093,
United States of America
Weiyao Li − Department of Polymer Science, The University of
Hannah Boyce − Department of Chemistry, Northwestern
University, Evanston, Illinois 60208, United States of America
Haochuan Mao − Department of Chemistry and Institute for
natriegens. W.C., M.P.T., and N.C.G. cowrote the manuscript
with contributions from all authors. All authors discussed and
interpreted the results and revised the manuscript.
Funding
The work was supported by the Air Force Office of Scientific
Research through a MURI Grant (FA9550-18-1-0142), and
supplemental grant (AFOSR FA9550-18-1-0477) and FWO
grant G007117N by the Assistant Secretary of Defense for
Research and Engineering (ASD (R&E)) through the Applied
Research for Advancement of S&T Priorities Synthetic Biology
for Military Environments program which supports Z. W. EPR
spectroscopy was supported by the National Science
Foundation under Award NO. CHE-1900422 (M.R.W.). H.
B. was supported primarily by the National Science
Foundation under NSF Award Number EEC-1757618.
Xuhao Zhou − Department of Chemistry, Northwestern
Notes
The authors declare the following competing financial
interest(s): N. C. G. and W. C. have filed a provisional patent
US 62/928,129 and are listed as inventors for selenium-
containing analogues of pheomelanin, related materials, and
synthetic methods.
Hao Sun − Department of Chemistry and Department of
Materials Science and Engineering, Department of Biomedical
Engineering, Department of Pharmacology, International
Institute for Nanotechnology, Simpson-Querrey Institute,
Chemistry of Life Processes Institute, Lurie Cancer Center,
Matthew P. Thompson − Department of Chemistry and
Department of Materials Science and Engineering, Department
of Biomedical Engineering, Department of Pharmacology,
International Institute for Nanotechnology, Simpson-Querrey
Institute, Chemistry of Life Processes Institute, Lurie Cancer
Center, Northwestern University, Evanston, Illinois 60208,
United States of America
Claudia Battistella − Department of Chemistry and Department
of Materials Science and Engineering, Department of Biomedical
Engineering, Department of Pharmacology, International
Institute for Nanotechnology, Simpson-Querrey Institute,
Chemistry of Life Processes Institute, Lurie Cancer Center,
Northwestern University, Evanston, Illinois 60208, United
ACKNOWLEDGMENTS
■
The authors thank Paul Mehl in the Flow Cytometry Core
facility at Northwestern University. We thank Matthew Clutter
at the Center for Molecular Innovation and Drug Discovery at
Northwestern University for helpful discussions in the design
of X-ray radiation experiments. The authors acknowledge the
aid of Prof. Bethany Perez-White in the department of
dermatology at Northwestern Feinberg School of Medicine
for providing NHEK cells and for lending her expertise in
keratinocyte cell culture. We thank Prof. Dimitre H. Hristov in
the Department of Radiation Oncology, Stanford University
for help in the design of radiation experiments and Prof
Vythialingam Sathiaseelan at Northwestern Feinberg School of
Medicine for providing us with X-ray film. Finally, we thank
Sara Fernandez Dunne at Northwestern’s High Throughput
Analysis Core for her assistance with conducting RT-PCR
experiments. We would also like to thank Northwestern
NUANCE BioCryo staff scientists Eric W. Roth and Charlene
Wilke for their assistance in TEM cell embedding and
microtomy.
Michael R. Wasielewski − Department of Chemistry and
Institute for Sustainability and Energy, Northwestern University,
Ali Dhinojwala − Department of Polymer Science, The
ABBREVIATIONS
■
SeNP, selenomelanin nanoparticle; NP, nanoparticle; Sec,
selenocysteine; SECIS, SElenoCysteine Insertion Sequence; L-
DOPA, L-3,4-dihydroxyphenylalanine; EPR, electron para-
magnetic resonance; XPS, X-ray photoelectron spectroscopy;
NHEK, neonatal human epidermal keratinocytes; PDA NP,
polydopamine nanoparticle; TEM, transmission electron
microscopy; FTIR, Fourier-transform infrared spectroscopy;
ROS, reactive oxygen species; HPLC, high performance liquid
chromatography; ICP-OES, inductively coupled plasma optical
emission spectrometry; ssNMR, solid-state nuclear magnetic
resonance; PNPs, Pheomelanin nanoparticles; CLSM, confocal
laser scanning microscopy; STEM, Scanning transmission
electron microscopy; WGA, wheat germ agglutinin; DCFDA,
Author Contributions
W.C. and N.C.G. conceived the project and designed the
experiments. W. C. conducted the majority of experiments.
N.C.M. assisted with NHEK cell culture and obtained/
analyzed STEM and SEM images. Q.Z.N. and M.D.B.
1
3
designed, performed, and interpreted solid-state C NMR.
W.L. and A.D. measured the refractive index of selenomela-
nins. H.B. performed NP stability tests for aggregation by DLS.
C.B. assisted with cell culture. H.M. and M.R.W. performed
EPR. H.S. obtained CD spectra. X.Z. performed and analyzed
radical scavenging experiments. M.D.S. obtained samples and
developed methodologies for extraction of the natural
pheomelanin samples. Z.W. performed biosynthesis with V.
2
′,7’−dichlorofluorescein diacetate; DPPH, 2,2-diphenyl-1-
(2,4,6-trinitrophenyl) hydrazyl; RT-PCR, reverse transcription
polymerase chain reaction; CDKN1a, cyclin-dependent kinase
inhibitor 1a
G
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX