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) |
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Pages (from-to) | 4046-4054 |
Number of pages | 9 |
Journal | ACS nano |
Volume | 10 |
Issue number | 4 |
DOIs | |
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