Multimodal Imaging of Pancreatic Cancer Microenvironment in Response to an Antiglycolytic Drug.
Elnaz SheikhKirti AgrawalSanjit RoyDavid BurkFabrizio DonnarummaYoung H KoPraveen Kumar GuttulaNrusingh C BiswalHem D ShuklaManas Ranjan GartiaPublished in: Advanced healthcare materials (2023)
Lipid metabolism and glycolysis play crucial roles in the progression and metastasis of cancer, and the use of 3-bromopyruvate (3-BP) as an antiglycolytic agent has shown promise in killing pancreatic cancer cells. However, developing an effective strategy to avoid chemoresistance requires the ability to probe the interaction of cancer drugs with complex tumor-associated microenvironments (TAMs). Unfortunately, no robust and multiplexed molecular imaging technology is currently available to analyze TAMs. In this study, we demonstrate the simultaneous profiling of three protein biomarkers using SERS nanotags and antibody-functionalized nanoparticles in a syngeneic mouse model of pancreatic cancer. This allows for comprehensive information about biomarkers and TAM alterations before and after treatment. Our multimodal imaging techniques include surface-enhanced Raman spectroscopy (SERS), immunohistochemistry, polarized light microscopy, second harmonic generation (SHG) microscopy, fluorescence lifetime imaging microscopy (FLIM), and untargeted liquid chromatography and mass spectrometry (LC-MS) analysis. The study reveals the efficacy of 3-BP in treating pancreatic cancer and identifies drug treatment-induced lipid species remodeling and associated pathways through bioinformatics analysis. This article is protected by copyright. All rights reserved.
Keyphrases
- high resolution
- mass spectrometry
- raman spectroscopy
- liquid chromatography
- single molecule
- papillary thyroid
- mouse model
- gold nanoparticles
- label free
- high throughput
- high speed
- high resolution mass spectrometry
- bioinformatics analysis
- optical coherence tomography
- quantum dots
- sensitive detection
- tandem mass spectrometry
- drug induced
- single cell
- emergency department
- squamous cell carcinoma
- high performance liquid chromatography
- adverse drug
- fluorescence imaging
- childhood cancer
- big data
- living cells
- lymph node metastasis
- endothelial cells
- deep learning
- small molecule
- solid phase extraction
- molecularly imprinted
- replacement therapy
- photodynamic therapy
- electronic health record