DNA Origami-Cyanine Nanocomplex for Precision Imaging of KRAS-Mutant Pancreatic Cancer Cells

Hye ran Moon; Yancheng Du; Sae Rome Choi; Seongmin Seo; Cih Cheng; Bennett D. Elzey; Jong Hyun Choi; Bumsoo Han

doi:10.1002/advs.202410278

DNA Origami-Cyanine Nanocomplex for Precision Imaging of KRAS-Mutant Pancreatic Cancer Cells

Hye ran Moon, Yancheng Du, Sae Rome Choi, Seongmin Seo, Cih Cheng, Bennett D. Elzey, Jong Hyun Choi, Bumsoo Han

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	2410278
Journal	Advanced Science
Volume	12
Issue number	19
Early online date	Feb 14 2025
DOIs	https://doi.org/10.1002/advs.202410278
State	E-pub ahead of print - Feb 14 2025

Keywords

DNA origami
KRAS mutation
macropinocytosis
microfluidic tumor model
nanoparticle delivery
stroma tissue

ASJC Scopus subject areas

Medicine (miscellaneous)
General Chemical Engineering
General Materials Science
Biochemistry, Genetics and Molecular Biology (miscellaneous)
General Engineering
General Physics and Astronomy

Online availability

10.1002/advs.202410278License: CC BY

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title = "DNA Origami-Cyanine Nanocomplex for Precision Imaging of KRAS-Mutant Pancreatic Cancer Cells",

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.",

keywords = "DNA origami, KRAS mutation, macropinocytosis, microfluidic tumor model, nanoparticle delivery, stroma tissue",

author = "Moon, {Hye ran} and Yancheng Du and Choi, {Sae Rome} and Seongmin Seo and Cih Cheng and Elzey, {Bennett D.} and Choi, {Jong Hyun} and Bumsoo Han",

note = "H.R.M., Y.D., and S.R.C. contributed equally to this work. The authors thank Drs. C. Lin and L. Liu for providing the design of DNA origami used. The authors also acknowledge the assistance of MacKenzie Mcintosh and the Purdue University Histology Research Laboratory and Huimin Zhang and Hui Xu from University of Illinois at Urbana\u2010Champaign Tumor Engineering and Phenotyping Shared Resource. This work was partially supported by grants from the National Institutes of Health (U01 HL143403, R01 CA254110, U01 CA274304 to BH) and the National Science Foundation (MCB\u20102134603). H.M. was partially supported by the Purdue University Center for Cancer Research (P30 CA023168) and a Postdoc Challenge Award from Indiana Clinical and Translational Sciences Institute which is funded in part by Award Number UM1TR004402 from the National Institutes of Health.",

year = "2025",

month = feb,

day = "14",

doi = "10.1002/advs.202410278",

language = "English (US)",

volume = "12",

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T1 - DNA Origami-Cyanine Nanocomplex for Precision Imaging of KRAS-Mutant Pancreatic Cancer Cells

AU - Moon, Hye ran

AU - Du, Yancheng

AU - Choi, Sae Rome

AU - Seo, Seongmin

AU - Cheng, Cih

AU - Elzey, Bennett D.

AU - Choi, Jong Hyun

AU - Han, Bumsoo

N1 - H.R.M., Y.D., and S.R.C. contributed equally to this work. The authors thank Drs. C. Lin and L. Liu for providing the design of DNA origami used. The authors also acknowledge the assistance of MacKenzie Mcintosh and the Purdue University Histology Research Laboratory and Huimin Zhang and Hui Xu from University of Illinois at Urbana\u2010Champaign Tumor Engineering and Phenotyping Shared Resource. This work was partially supported by grants from the National Institutes of Health (U01 HL143403, R01 CA254110, U01 CA274304 to BH) and the National Science Foundation (MCB\u20102134603). H.M. was partially supported by the Purdue University Center for Cancer Research (P30 CA023168) and a Postdoc Challenge Award from Indiana Clinical and Translational Sciences Institute which is funded in part by Award Number UM1TR004402 from the National Institutes of Health.

PY - 2025/2/14

Y1 - 2025/2/14

N2 - 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.

AB - 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.

KW - DNA origami

KW - KRAS mutation

KW - macropinocytosis

KW - microfluidic tumor model

KW - nanoparticle delivery

KW - stroma tissue

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UR - http://www.scopus.com/inward/citedby.url?scp=85219723468&partnerID=8YFLogxK

U2 - 10.1002/advs.202410278

DO - 10.1002/advs.202410278

M3 - Article

C2 - 39951277

AN - SCOPUS:85219723468

SN - 2198-3844

VL - 12

JO - Advanced Science

JF - Advanced Science

IS - 19

M1 - 2410278

ER -

DNA Origami-Cyanine Nanocomplex for Precision Imaging of KRAS-Mutant Pancreatic Cancer Cells

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DNA origami guides new possibilities in the fight against pancreatic cancer

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DNA Origami-Cyanine Nanocomplex for Precision Imaging of KRAS-Mutant Pancreatic Cancer Cells

Abstract

Keywords

ASJC Scopus subject areas

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DNA origami guides new possibilities in the fight against pancreatic cancer

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