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Harnessing nanotechnology to expand the toolbox of chemical biology


Although nanotechnology often addresses biomedical needs, nanoscale tools can also facilitate broad biological discovery. Nanoscale delivery, imaging, biosensing, and bioreactor technologies may address unmet questions at the interface between chemistry and biology. Currently, many chemical biologists do not include nanomaterials in their toolbox, and few investigators develop nanomaterials in the context of chemical tools to answer biological questions. We reason that the two fields are ripe with opportunity for greater synergy. Nanotechnologies can expand the utility of chemical tools in the hands of chemical biologists, for example, through controlled delivery of reactive and/or toxic compounds or signal-binding events of small molecules in living systems. Conversely, chemical biologists can work with nanotechnologists to address challenging biological questions that are inaccessible to both communities. This Perspective aims to introduce the chemical biology community to nanotechnologies that may expand their methodologies while inspiring nanotechnologists to address questions relevant to chemical biology.

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Fig. 1: Major classes of potential contributions of nanotechnology to chemical biology.
Fig. 2: Nanoparticle-based delivery of transition-metal catalysts for intracellular chemical reactions.
Fig. 3: Representative examples of enzymatic nanoreactors.
Fig. 4: Nanotechnologies for imaging applications.
Fig. 5: Examples of optical properties unique to certain nanomaterial imaging agents.
Fig. 6: Examples of nanoscale sensor strategies.


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This work was supported in part by the Cancer Center Support Grant (D.A.H., M.L.: P30-CA008748), the NIH New Innovator Award (D.A.H.: DP2-HD075698), National Institute of Diabetes and Digestive and Kidney Diseases (D.A.H.: R01-DK114321), National Cancer Institute (D.A.H.: R01-CA215719), National Institute of Neurological Disorders and Stroke (D.A.H.: R01-NS116353), Clinical and Translational Science Center Grant (D.A.H.: UL1-TR002384), National Institute of General Medical Sciences (M.L.: R01GM096056, R01GM120570, R35GM134878), the National Science Foundation CAREER Award (D.A.H: 1752506), the American Cancer Society Research Scholar Grant (D.A.H.: GC230452), Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research, the Experimental Therapeutics Center (D.A.H., M.L.), the Pershing Square Sohn Cancer Research Alliance (D.A.H.), the Honorable Tina Brozman Foundation for Ovarian Cancer Research (D.A.H.), the Expect Miracles Foundation – Financial Services Against Cancer (D.A.H.), the Anna Fuller Fund (D.A.H.), the Louis V. Gerstner Jr. Young Investigator’s Fund (D.A.H.), the Frank A. Howard Scholars Program (D.A.H.), Cycle for Survival (D.A.H.), the Alan and Sandra Gerry Metastasis Research Initiative (D.A.H.), the Imaging & Radiation Sciences Program (D.A.H.), and the Center for Molecular Imaging and Nanotechnology of Memorial Sloan Kettering Cancer (D.A.H.), Starr Cancer Consortium (M.L.), Functional Genomic Initiative (M.L.), the Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center (M.L.), Tri-institute Program of Chemical Biology (S.C.). R.M.W. was supported by the City College of New York Grove School of Engineering, the Ovarian Cancer Research Fund (Ann Schreiber Mentored Investigator Award 370463), and the American Heart Association Postdoctoral Fellowship (17POST33650043).

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R.M.W., S.C., J.B.U., M.L., and D.A.H. conceived of the manuscript; all authors reviewed the literature and drafted the manuscript.

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Correspondence to Januka Budhathoki-Uprety or Minkui Luo or Daniel A. Heller.

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Competing interests

D.A.H. is a cofounder and officer with equity interest in Goldilocks Therapeutics, Inc., LipidSense, Inc., and Nirova BioSense, Inc. D.A.H. is a member of the scientific advisory boards of Concarlo Holdings, LLC and Nanorobotics, Inc. R.M.W. is a scientific advisor with equity interest in Goldilocks Therapeutics, Inc. M.L. is a member of the scientific advisory board of Epi One, Inc. P.V.J. is a cofounder and officer with equity interest in LipidSense, Inc. and an officer of Nirova BioSense, Inc.

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Williams, R.M., Chen, S., Langenbacher, R.E. et al. Harnessing nanotechnology to expand the toolbox of chemical biology. Nat Chem Biol 17, 129–137 (2021).

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