13 research outputs found
Soft nanomaterials analysed by in situ liquid TEM: Towards high resolution characterisation of nanoparticles in motion
No full textSummaryIn this article we present in situ transmission electron microscopy (TEM) of soft, synthetic nanoparticles with a comparative analysis using conventional TEM methods. This comparison is made with the simple aim of describing what is an unprecedented example of in situ imaging by TEM. However, we contend the technique will quickly become essential in the characterisation of analogous systems, especially where dynamics are of interest in the solvated state. In this case, particles were studied which were obtained from the direct polymerisation of an oxaliplatin analogue, designed for an ongoing programme in novel chemotherapeutic delivery systems. The resulting nanoparticles provided sufficient contrast for facile imaging in situ, and point towards key design parameters that enable this new characterisation approach for organic nanomaterials. We describe the preparation of the synthetic nanoparticles together with their characterisation in liquid water. Finally, we provide a future perspective of this technique for the analysis of soft and dynamic nanomaterials and discussion the progress which needs to be made in order to bring in situ liquid TEM to its full potential
Synthesis, Characterization, and in vitro Antiproliferative Activity of [Salophene]platinum(II) Complexes
No full text
Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded Nanoparticles Imaged by Nanoscale Secondary Ion Mass Spectrometry and Fluorescence Microscopy
No full textIn nanomedicine, determining the
spatial distribution of particles
and drugs, together and apart, at high resolution within tissues,
remains a major challenge because each must have a different label
or detectable feature that can be observed with high sensitivity and
resolution. We prepared nanoparticles capable of enzyme-directed assembly
of particle therapeutics (EDAPT), containing an analogue of the Pt(II)-containing
drug oxaliplatin, an 15N-labeled monomer in the hydrophobic
block of the backbone of the polymer, the near-infrared dye Cy5.5,
and a peptide that is a substrate for tumor metalloproteinases in
the hydrophilic block. When these particles reach an environment rich
in tumor associated proteases, the hydrophilic peptide substrate is
cleaved, causing the particles to accumulate through a morphology
transition, locking them in the tumor extracellular matrix. To evaluate
the distribution of drug and EDAPT carrier in vivo, the localization of the isotopically labeled polymer backbone was
compared to that of Pt by nanoscale secondary ion mass spectrometry
(NanoSIMS). The correlation of NanoSIMS with super-resolution fluorescence
microscopy revealed the release of the drug from the nanocarrier and
colocalization with cellular DNA within tumor tissue. The results
confirmed the dependence of particle accumulation and Pt(II) drug
delivery on the presence of a Matrix Metalloproteinase (MMP) substrate
and demonstrated antitumor activity. We conclude that these techniques
are powerful for the elucidation of the localization of cargo and
carrier, and enable a high-resolution assessment of their performance
following in vivo delivery
Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded Nanoparticles Imaged by Nanoscale Secondary Ion Mass Spectrometry and Fluorescence Microscopy.
No full textCellular Delivery of Nanoparticles Revealed with Combined Optical and Isotopic Nanoscopy
No full textCellular Delivery of Nanoparticles Revealed with Combined Optical and Isotopic Nanoscopy
No full textDirect 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
Dynamics of soft nanomaterials captured by transmission electron microscopy in liquid water
No full text\u3cp\u3eIn this paper we present in situ transmission electron microscopy of synthetic polymeric nanoparticles with emphasis on capturing motion in a solvated, aqueous state. The nanoparticles studied were obtained from the direct polymerization of a Pt(II)-containing monomer. The resulting structures provided sufficient contrast for facile imaging in situ. We contend that this technique will quickly become essential in the characterization of analogous systems, especially where dynamics are of interest in the solvated state. We describe the preparation of the synthetic micellar nanoparticles together with their characterization and motion in liquid water with comparison to conventional electron microscopy analyses.\u3c/p\u3
