Research Article

Elucidating a Tumor-Selective Nanoparticle Delivery Mechanism at the Colorectal Lumen–Tumor Interface for Precise Local Cancer Therapy

Juho Lee

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Dongmin Kwak,

Dongmin Kwak

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Hyunwoo Kim,

Hyunwoo Kim

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Muneeb Ullah,

Muneeb Ullah

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Jihyun Kim,

Jihyun Kim

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Muhammad Naeem,

Muhammad Naeem

Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Punjab, 46000 Pakistan

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Seonghwan Hwang,

Seonghwan Hwang

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Eunok Im,

Eunok Im

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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In-Soo Yoon,

In-Soo Yoon

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Yunjin Jung,

Yunjin Jung

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Jin-Wook Yoo,

Corresponding Author

Jin-Wook Yoo

[email protected]

orcid.org/0000-0001-5216-5518

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

E-mail: [email protected]

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Juho Lee,

Juho Lee

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Dongmin Kwak,

Dongmin Kwak

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Hyunwoo Kim,

Hyunwoo Kim

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Muneeb Ullah,

Muneeb Ullah

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Jihyun Kim,

Jihyun Kim

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Muhammad Naeem,

Muhammad Naeem

Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Punjab, 46000 Pakistan

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Seonghwan Hwang,

Seonghwan Hwang

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Eunok Im,

Eunok Im

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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In-Soo Yoon,

In-Soo Yoon

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Yunjin Jung,

Yunjin Jung

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

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Jin-Wook Yoo,

Corresponding Author

Jin-Wook Yoo

[email protected]

orcid.org/0000-0001-5216-5518

College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea

E-mail: [email protected]

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First published: 19 January 2025

https://doi.org/10.1002/smll.202409994

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Abstract

Although various colorectal cancer (CRC)-targeted nanoparticles have been developed to selectively deliver anticancer agents to tumor tissues, severe off-target side effects still persist due to unwanted systemic nanoparticle distribution, limiting the therapeutic outcome. Here, by elucidating a tumor-selective nanoparticle delivery mechanism occurring at the colorectal lumen–tumor interface, an alternative CRC-targeted delivery route is proposed, which enables highly tumor-selective delivery without systemic distribution, through direct drug delivery from the outside of the body (colorectal lumen) to tumors in the colorectum. Owing to the presence of accessible tumor-specific receptors such as CD44 at the colorectal lumen–tumor interface, but not at the colorectal lumen–normal tissue interface, colorectal luminal surface (CLS)-targeting ligand-functionalized nanoparticles selectively accumulate in CRC tissues without systemic distribution, resulting in successful local CRC therapy. The findings suggest that CLS-targeted lumen-to-tumor delivery can be a suitable strategy for highly CRC-specific drug delivery for precise local CRC therapy.

Conflict of Interest

The authors declare no conflict of interest.

Open Research

Data Availability Statement

Data are available in the article and Supporting Information.

Supporting Information

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Volume21, Issue9

March 5, 2025

2409994

Filename	Description
smll202409994-sup-0001-SupMat.docx4.9 MB	Supporting Information
smll202409994-sup-0002-VideoS1.mp46 MB	Supplemental Video 1
smll202409994-sup-0003-VideoS2.mp45.2 MB	Supplemental Video 2
smll202409994-sup-0004-VideoS3.mp46.1 MB	Supplemental Video 3
smll202409994-sup-0005-VideoS4.mp410.7 MB	Supplemental Video 4

Elucidating a Tumor-Selective Nanoparticle Delivery Mechanism at the Colorectal Lumen–Tumor Interface for Precise Local Cancer Therapy

Abstract

Conflict of Interest

Open Research

Data Availability Statement

Supporting Information

References

References

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Elucidating a Tumor-Selective Nanoparticle Delivery Mechanism at the Colorectal Lumen–Tumor Interface for Precise Local Cancer Therapy

Abstract

Conflict of Interest

Open Research

Data Availability Statement

Supporting Information

References

References

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