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Adv. Sci., Feb 14 2025, | https://doi.org/10.1002/advs.202410278
DNA Origami-Cyanine Nanocomplex for Precision Imaging of KRAS-Mutant Pancreatic Cancer Cells
Hye-Ran Moon 1 †, Yancheng Du 1 †, Sae Rome Choi 1 2 3 †, Seongmin Seo 1, Cih Cheng 1, Bennett D Elzey 4 5, Jong Hyun Choi 1 *, Bumsoo Han 1 2 3 4 6 *
1School of Mechanical Engineering, Purdue University, West Lafayette, IN, 47907, USA.
2Department of Mechanical Science and Engineering, Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
3Cancer Center at Illinois, Materials Research Laboratory, Institute of Genomic Biology, Beckman Institute, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
4Purdue Institute for Cancer Research, Purdue University, West Lafayette, IN, 47907, USA.
5Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, 47907, USA.
6Chan Zuckerberg Biohub Chicago, Chicago, IL, 60642, USA.
2Department of Mechanical Science and Engineering, Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
3Cancer Center at Illinois, Materials Research Laboratory, Institute of Genomic Biology, Beckman Institute, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
4Purdue Institute for Cancer Research, Purdue University, West Lafayette, IN, 47907, USA.
5Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, 47907, USA.
6Chan Zuckerberg Biohub Chicago, Chicago, IL, 60642, USA.
†H.R.M., Y.D., and S.R.C. contributed equally to this work.
*Corresponding authors: correspondence to Jong Hyun Choi or Bumsoo Han
*Corresponding authors: correspondence to Jong Hyun Choi or Bumsoo Han
Abstract
Selective delivery of imaging agents to pancreatic cancer cells (PCCs) within the highly desmoplastic tumors of pancreatic ductal adenocarcinoma (PDAC) represents a significant advancement. This approach allows for precise labeling of PCCs while excluding cancer-associated fibroblasts (CAFs), thereby enhancing both research and diagnostic capabilities. Additionally, it holds the potential to target and eliminate PCCs precisely without harming the surrounding stromal cells in the PDAC tumor microenvironment (TME). In this study, DNA origami-cyanine (Do-Cy) nanocomplexes are synthesized to image KRAS-mutant PCCs selectively in the PDAC TME. These Do-Cy nanocomplexes are hypothesized to be internalized preferentially to KRAS-mutant PCCs over CAFs via elevated macropinocytosis. Several designs of Do-Cy nanocomplexes are synthesized and characterized their cellular uptake using both engineered in vitro and xenograft pancreatic cancer models. The results are further discussed for the implication of precision delivery of therapeutic and imaging agents to KRAS-mutant cancers.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-24)
- 국외 연구진
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