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1.
J Control Release ; 357: 31-39, 2023 05.
Article in English | MEDLINE | ID: mdl-36948419

ABSTRACT

Bioorthogonal catalysis via transition metal catalysts (TMCs) enables the generation of therapeutics locally through chemical reactions not accessible by biological systems. This localization can enhance the efficacy of anticancer treatment while minimizing off-target effects. The encapsulation of TMCs into nanomaterials generates "nanozymes" to activate imaging and therapeutic agents. Here, we report the use of cationic bioorthogonal nanozymes to create localized "drug factories" for cancer therapy in vivo. These nanozymes remained present at the tumor site at least seven days after a single injection due to the interactions between cationic surface ligands and negatively charged cell membranes and tissue components. The prodrug was then administered systemically, and the nanozymes continuously converted the non-toxic molecules into active drugs locally. This strategy substantially reduced the tumor growth in an aggressive breast cancer model, with significantly reduced liver damage compared to traditional chemotherapy.


Subject(s)
Breast Neoplasms , Nanostructures , Humans , Female , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/drug therapy , Diagnostic Imaging , Catalysis , Cell Membrane
2.
Front Mol Biosci ; 9: 785232, 2022.
Article in English | MEDLINE | ID: mdl-35463966

ABSTRACT

The status of metabolomics as a scientific branch has evolved from proof-of-concept to applications in science, particularly in medical research. To comprehensively evaluate disease metabolomics, multiplatform approaches of NMR combining with mass spectrometry (MS) have been investigated and reported. This mixed-methods approach allows for the exploitation of each individual technique's unique advantages to maximize results. In this article, we present our findings from combined NMR and MS imaging (MSI) analysis of human lung and prostate cancers. We further provide critical discussions of the current status of NMR and MS combined human prostate and lung cancer metabolomics studies to emphasize the enhanced metabolomics ability of the multiplatform approach.

3.
Analyst ; 146(24): 7720-7729, 2021 Dec 06.
Article in English | MEDLINE | ID: mdl-34821231

ABSTRACT

Laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS) imaging and matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) are complementary methods that measure distributions of elements and biomolecules in tissue sections. Quantitative correlations of the information provided by these two imaging modalities requires that the datasets be registered in the same coordinate system, allowing for pixel-by-pixel comparisons. We describe here a computational workflow written in Python that accomplishes this registration, even for adjacent tissue sections, with accuracies within ±50 µm. The value of this registration process is demonstrated by correlating images of tissue sections from mice injected with gold nanomaterial drug delivery systems. Quantitative correlations of the nanomaterial delivery vehicle, as detected by LA-ICP-MS imaging, with biochemical changes, as detected by MALDI-MSI, provide deeper insight into how nanomaterial delivery systems influence lipid biochemistry in tissues. Moreover, the registration process allows the more precise images associated with LA-ICP-MS imaging to be leveraged to achieve improved segmentation in MALDI-MS images, resulting in the identification of lipids that are most associated with different sub-organ regions in tissues.


Subject(s)
Laser Therapy , Nanostructures , Animals , Gold , Mice , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Tissue Distribution
4.
Nanoscale ; 13(29): 12623-12633, 2021 Aug 07.
Article in English | MEDLINE | ID: mdl-34264256

ABSTRACT

Nanomaterial-based platforms are promising vehicles for the controlled delivery of therapeutics. For these systems to be both efficacious and safe, it is essential to understand where the carriers accumulate and to reveal the site-specific biochemical effects they produce in vivo. Here, a dual-mode mass spectrometry imaging (MSI) method is used to evaluate the distributions and biochemical effects of anti-TNF-α nanoparticle stabilized capsules (NPSCs) in mice. It is found that most of the anticipated biochemical changes occur in sub-organ regions that are separate from where the nanomaterials accumulate. In particular, TNF-α-specific lipid biomarker levels change in immune cell-rich regions of organs, while the NPSCs accumulate in spatially isolated filtration regions. Biochemical changes that are associated with the nanomaterials themselves are also observed, demonstrating the power of matrix-assisted laser desorption/ionization (MALDI) MSI to reveal markers indicating possible off-target effects of the delivery agent. This comprehensive assessment using MSI provides spatial context of nanomaterial distributions and efficacy that cannot be easily achieved with other imaging methods, demonstrating the power of MSI to evaluate both expected and unexpected outcomes associated with complex therapeutic delivery systems.


Subject(s)
Nanoparticles , Nanostructures , Animals , Capsules , Mice , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Tumor Necrosis Factor Inhibitors
5.
Anal Chem ; 92(2): 2011-2018, 2020 01 21.
Article in English | MEDLINE | ID: mdl-31825199

ABSTRACT

Nanomaterial-based drug delivery vehicles are able to deliver therapeutics in a controlled, targeted manner. Currently, however, there are limited analytical methods that can detect both nanomaterial distributions and their biochemical effects concurrently. In this study, we demonstrate that matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP-MSI) can be used together to obtain nanomaterial distributions and biochemical consequences. These studies employ nanoparticle-stabilized capsules (NPSCs) loaded with siRNA as a testbed. MALDI-MSI experiments on spleen tissues from intravenously injected mice indicate that NPSCs loaded with anti-TNF-α siRNA cause changes to the lipid composition in white pulp regions of the spleen, as anticipated, based on pathways known to be affected by TNF-α, whereas NPSCs loaded with scrambled siRNA do not cause the predicted changes. Interestingly, LA-ICP-MSI experiments reveal that the NPSCs primarily localize in the red pulp, suggesting that the observed changes in lipid composition are due to diffusive rather than localized effects on TNF-α production. Such information is only accessible by combining data from the two modalities, which we accomplish by using the heme signals from MALDI-MSI and iron signals from LA-ICP-MSI to overlay the images. Several unexpected changes in lipid composition also occur in regions where the NPSCs are found, suggesting that the NPSCs themselves can influence tissue biochemistry as well.


Subject(s)
Capsules/analysis , Nanoparticles/analysis , Spleen/chemistry , Animals , Capsules/administration & dosage , Capsules/metabolism , Drug Carriers/administration & dosage , Drug Carriers/analysis , Drug Carriers/metabolism , Injections, Intravenous , Mass Spectrometry , Mice , Nanoparticles/administration & dosage , Nanoparticles/metabolism , Spleen/metabolism , Tissue Distribution
6.
ACS Nano ; 10(7): 6731-6, 2016 07 26.
Article in English | MEDLINE | ID: mdl-27337000

ABSTRACT

Differentiation between cell surface-bound and internalized nanoparticles is challenging yet essential for accurately quantifying cellular uptake. Here, we describe a versatile mass spectrometry-based method that allows separate quantification of both cell surface-bound and internalized nanoparticles. This rapid method uses tuned laser fluencies to selectively desorb and ionize cell surface-bound cationic gold nanoparticles from intact cells, providing quantification of external particles. Overall nanoparticle quantities are obtained from the cell lysates, with subtraction of external particles from the total amount providing quantification of taken-up nanoparticles. The utility of this strategy was demonstrated through simultaneous quantitative determination of how cell-surface proteoglycans influence nanoparticle binding and uptake into cells.


Subject(s)
Cell Differentiation , Gold , Mass Spectrometry , Metal Nanoparticles , Cations , Cell Membrane , Nanoparticles
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