Cellular Delivery of Nanoparticles Revealed with Combined Optical and Isotopic Nanoscopy

Maria T. Proetto; Christopher R. Anderton; Dehong Hu; Craig J. Szymanski; Zihua Zhu; Joseph P. Patterson; Jacquelin K. Kammeyer; Lizanne G. Nilewski; Anthony M. Rush; Nia C. Bell; James E. Evans; Galya Orr; Stephen B. Howell; Nathan C. Gianneschi

doi:10.1021/acsnano.5b06477

Cellular Delivery of Nanoparticles Revealed with Combined Optical and Isotopic Nanoscopy

Maria T. Proetto, Christopher R. Anderton, Dehong Hu, Craig J. Szymanski, Zihua Zhu, Joseph P. Patterson, Jacquelin K. Kammeyer, Lizanne G. Nilewski, Anthony M. Rush, Nia C. Bell, James E. Evans, Galya Orr, Stephen B. Howell, Nathan C. Gianneschi^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

Direct polymerization of an oxaliplatin analogue was used to reproducibly generate amphiphiles in one pot, which consistently and spontaneously self-assemble into well-defined nanoparticles (NPs). Despite inefficient drug leakage in cell-free assays, the NPs were observed to be as cytotoxic as free oxaliplatin in cell culture experiments. We investigated this phenomenon by super-resolution fluorescence structured illumination microscopy (SIM) and nanoscale secondary ion mass spectrometry (NanoSIMS). In combination, these techniques revealed NPs are taken up via endocytic pathways before intracellular release of their cytotoxic cargo. As with other drug-carrying nanomaterials, these systems have potential as cellular delivery vehicles. However, high-resolution methods to track nanocarriers and their cargo at the micro- and nanoscale have been underutilized in general, limiting our understanding of their interactions with cells and tissues. We contend this type of combined optical and isotopic imaging strategy represents a powerful and potentially generalizable methodology for cellular tracking of nanocarriers and their cargo.

Original language	English (US)
Pages (from-to)	4046-4054
Number of pages	9
Journal	ACS nano
Volume	10
Issue number	4
DOIs	https://doi.org/10.1021/acsnano.5b06477
State	Published - Apr 26 2016

Funding

NIH Director?s New Innovator Award (DP2OD008724) and R01 grants R01EB011633, CA152185, and CA095298 are acknowledged. M.T.P. thanks the UCSD CRIN for a postdoctoral fellowship and the mentorship of Dr. A. Kummel within that program. We thank ARO for a DURIP grant (W911NF-13-1-0321) to purchase a PerkinElmer plate reader used in these studies. We acknowledge use of the UCSD Cryo-EM Facility, which is supported by NIH grant R37 GM-03350 to Dr. T. S. Baker and a gift from the Agouron Institute to UCSD. M.T.P. thanks the UCSD Neuroscience Microscopy Shared Facility, which is supported via the P30 NS047101 grant. M.T.P. also thanks Dr. D. Stramski and J. Tatarkiewicz from Scripps Institution of Oceanography, UCSD, for making available the NanoSight instrument. M.T.P. also thanks Dr. P.R. Castillo and C. MacIsaac from Scripps Institution of Oceanography, UCSD, for their assistance with the ICP-OES experiments.

Keywords

NanoSIMS
SIM
cytotoxicity
drug delivery
drug-loaded nanoparticles
fluorescence
platinum(II) complexes

ASJC Scopus subject areas

General Materials Science
General Engineering
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsnano.5b06477

Cite this

@article{15f1acf2d28d44efb951ce142cfd0cc8,

title = "Cellular Delivery of Nanoparticles Revealed with Combined Optical and Isotopic Nanoscopy",

abstract = "Direct polymerization of an oxaliplatin analogue was used to reproducibly generate amphiphiles in one pot, which consistently and spontaneously self-assemble into well-defined nanoparticles (NPs). Despite inefficient drug leakage in cell-free assays, the NPs were observed to be as cytotoxic as free oxaliplatin in cell culture experiments. We investigated this phenomenon by super-resolution fluorescence structured illumination microscopy (SIM) and nanoscale secondary ion mass spectrometry (NanoSIMS). In combination, these techniques revealed NPs are taken up via endocytic pathways before intracellular release of their cytotoxic cargo. As with other drug-carrying nanomaterials, these systems have potential as cellular delivery vehicles. However, high-resolution methods to track nanocarriers and their cargo at the micro- and nanoscale have been underutilized in general, limiting our understanding of their interactions with cells and tissues. We contend this type of combined optical and isotopic imaging strategy represents a powerful and potentially generalizable methodology for cellular tracking of nanocarriers and their cargo.",

keywords = "NanoSIMS, SIM, cytotoxicity, drug delivery, drug-loaded nanoparticles, fluorescence, platinum(II) complexes",

author = "Proetto, \{Maria T.\} and Anderton, \{Christopher R.\} and Dehong Hu and Szymanski, \{Craig J.\} and Zihua Zhu and Patterson, \{Joseph P.\} and Kammeyer, \{Jacquelin K.\} and Nilewski, \{Lizanne G.\} and Rush, \{Anthony M.\} and Bell, \{Nia C.\} and Evans, \{James E.\} and Galya Orr and Howell, \{Stephen B.\} and Gianneschi, \{Nathan C.\}",

note = "Funding Information: NIH Director?s New Innovator Award (DP2OD008724) and R01 grants R01EB011633, CA152185, and CA095298 are acknowledged. M.T.P. thanks the UCSD CRIN for a postdoctoral fellowship and the mentorship of Dr. A. Kummel within that program. We thank ARO for a DURIP grant (W911NF-13-1-0321) to purchase a PerkinElmer plate reader used in these studies. We acknowledge use of the UCSD Cryo-EM Facility, which is supported by NIH grant R37 GM-03350 to Dr. T. S. Baker and a gift from the Agouron Institute to UCSD. M.T.P. thanks the UCSD Neuroscience Microscopy Shared Facility, which is supported via the P30 NS047101 grant. M.T.P. also thanks Dr. D. Stramski and J. Tatarkiewicz from Scripps Institution of Oceanography, UCSD, for making available the NanoSight instrument. M.T.P. also thanks Dr. P.R. Castillo and C. MacIsaac from Scripps Institution of Oceanography, UCSD, for their assistance with the ICP-OES experiments. Publisher Copyright: {\textcopyright} 2016 American Chemical Society.",

year = "2016",

month = apr,

day = "26",

doi = "10.1021/acsnano.5b06477",

language = "English (US)",

volume = "10",

pages = "4046--4054",

journal = "ACS nano",

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T1 - Cellular Delivery of Nanoparticles Revealed with Combined Optical and Isotopic Nanoscopy

AU - Proetto, Maria T.

AU - Anderton, Christopher R.

AU - Hu, Dehong

AU - Szymanski, Craig J.

AU - Zhu, Zihua

AU - Patterson, Joseph P.

AU - Kammeyer, Jacquelin K.

AU - Nilewski, Lizanne G.

AU - Rush, Anthony M.

AU - Bell, Nia C.

AU - Evans, James E.

AU - Orr, Galya

AU - Howell, Stephen B.

AU - Gianneschi, Nathan C.

N1 - Funding Information: NIH Director?s New Innovator Award (DP2OD008724) and R01 grants R01EB011633, CA152185, and CA095298 are acknowledged. M.T.P. thanks the UCSD CRIN for a postdoctoral fellowship and the mentorship of Dr. A. Kummel within that program. We thank ARO for a DURIP grant (W911NF-13-1-0321) to purchase a PerkinElmer plate reader used in these studies. We acknowledge use of the UCSD Cryo-EM Facility, which is supported by NIH grant R37 GM-03350 to Dr. T. S. Baker and a gift from the Agouron Institute to UCSD. M.T.P. thanks the UCSD Neuroscience Microscopy Shared Facility, which is supported via the P30 NS047101 grant. M.T.P. also thanks Dr. D. Stramski and J. Tatarkiewicz from Scripps Institution of Oceanography, UCSD, for making available the NanoSight instrument. M.T.P. also thanks Dr. P.R. Castillo and C. MacIsaac from Scripps Institution of Oceanography, UCSD, for their assistance with the ICP-OES experiments. Publisher Copyright: © 2016 American Chemical Society.

PY - 2016/4/26

Y1 - 2016/4/26

N2 - Direct polymerization of an oxaliplatin analogue was used to reproducibly generate amphiphiles in one pot, which consistently and spontaneously self-assemble into well-defined nanoparticles (NPs). Despite inefficient drug leakage in cell-free assays, the NPs were observed to be as cytotoxic as free oxaliplatin in cell culture experiments. We investigated this phenomenon by super-resolution fluorescence structured illumination microscopy (SIM) and nanoscale secondary ion mass spectrometry (NanoSIMS). In combination, these techniques revealed NPs are taken up via endocytic pathways before intracellular release of their cytotoxic cargo. As with other drug-carrying nanomaterials, these systems have potential as cellular delivery vehicles. However, high-resolution methods to track nanocarriers and their cargo at the micro- and nanoscale have been underutilized in general, limiting our understanding of their interactions with cells and tissues. We contend this type of combined optical and isotopic imaging strategy represents a powerful and potentially generalizable methodology for cellular tracking of nanocarriers and their cargo.

AB - Direct polymerization of an oxaliplatin analogue was used to reproducibly generate amphiphiles in one pot, which consistently and spontaneously self-assemble into well-defined nanoparticles (NPs). Despite inefficient drug leakage in cell-free assays, the NPs were observed to be as cytotoxic as free oxaliplatin in cell culture experiments. We investigated this phenomenon by super-resolution fluorescence structured illumination microscopy (SIM) and nanoscale secondary ion mass spectrometry (NanoSIMS). In combination, these techniques revealed NPs are taken up via endocytic pathways before intracellular release of their cytotoxic cargo. As with other drug-carrying nanomaterials, these systems have potential as cellular delivery vehicles. However, high-resolution methods to track nanocarriers and their cargo at the micro- and nanoscale have been underutilized in general, limiting our understanding of their interactions with cells and tissues. We contend this type of combined optical and isotopic imaging strategy represents a powerful and potentially generalizable methodology for cellular tracking of nanocarriers and their cargo.

KW - NanoSIMS

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KW - drug delivery

KW - drug-loaded nanoparticles

KW - fluorescence

KW - platinum(II) complexes

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Cellular Delivery of Nanoparticles Revealed with Combined Optical and Isotopic Nanoscopy

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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