Colorectal cancer lung metastasis treatment with polymer–drug nanoparticles

Piotr Rychahou; Younsoo Bae; Derek Reichel; Yekaterina Y. Zaytseva; Eun Y. Lee; Dana Napier; Heidi L. Weiss; Nick Roller; Heather Frohman; Anh Thu Le; B. Mark Evers

doi:10.1016/j.jconrel.2018.02.008

Colorectal cancer lung metastasis treatment with polymer–drug nanoparticles

Piotr Rychahou, Younsoo Bae, Derek Reichel, Yekaterina Y. Zaytseva, Eun Y. Lee, Dana Napier, Heidi L. Weiss, Nick Roller, Heather Frohman, Anh Thu Le, B. Mark Evers

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

42 Scopus citations

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States; the predominant cause for mortality is metastasis to distant organs (e.g., lung). A major problem limiting the success of chemotherapy in metastatic CRC is the inability to target tumor tissues selectively and avoid severe side effects to normal tissues and organs. Here, we demonstrate polymeric nanoparticles (PNPs) entrapping chemotherapeutic agents provide a new therapeutic option for treating CRC that has metastasized to the lung. PNPs assembled from FDA approved biocompatible block copolymer accumulated predominantly in lung tissue. PNPs showed negligible accumulation in liver, spleen and kidneys, which was confirmed by fluorescent nanoparticle imaging and analysis of PI3K inhibition in the organs. PNPs entrapping PI3K inhibitors (i.e., wortmannin and PX866) suppressed CRC lung metastasis growth, and SN-38-loaded PNPs completely eliminated CRC lung metastasis. Our results demonstrate that polymer-drug nanoparticles offer a new approach to reduce toxicity of cancer therapy and has the potential to improve outcomes for patients with lung metastasis.

Original language	English
Pages (from-to)	85-91
Number of pages	7
Journal	Journal of Controlled Release
Volume	275
DOIs	https://doi.org/10.1016/j.jconrel.2018.02.008
State	Published - Apr 10 2018

Bibliographical note

Funding Information:
The authors thank the Markey Cancer Center's Research Communications Office for help with manuscript preparation. We also thank the Biostatistics and Bioinformatics and the Biospecimen Procurement and Translational Pathology Shared Resource Facilities of the Markey Cancer Center for statistical analysis and histologic assessment, respectively. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the grant funding agencies. This study was supported by grants P30 CA177558 , R01 CA195573 , and R01 DK048498 from the National Institutes of Health (NIH).

Publisher Copyright:
© 2018 The Authors

Keywords

CRC lung metastasis
Colorectal cancer
Nanoparticle therapeutics
PI3K inhibitors
Polymeric nanoparticles

ASJC Scopus subject areas

Pharmaceutical Science

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jconrel.2018.02.008

Cite this

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title = "Colorectal cancer lung metastasis treatment with polymer–drug nanoparticles",

abstract = "Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States; the predominant cause for mortality is metastasis to distant organs (e.g., lung). A major problem limiting the success of chemotherapy in metastatic CRC is the inability to target tumor tissues selectively and avoid severe side effects to normal tissues and organs. Here, we demonstrate polymeric nanoparticles (PNPs) entrapping chemotherapeutic agents provide a new therapeutic option for treating CRC that has metastasized to the lung. PNPs assembled from FDA approved biocompatible block copolymer accumulated predominantly in lung tissue. PNPs showed negligible accumulation in liver, spleen and kidneys, which was confirmed by fluorescent nanoparticle imaging and analysis of PI3K inhibition in the organs. PNPs entrapping PI3K inhibitors (i.e., wortmannin and PX866) suppressed CRC lung metastasis growth, and SN-38-loaded PNPs completely eliminated CRC lung metastasis. Our results demonstrate that polymer-drug nanoparticles offer a new approach to reduce toxicity of cancer therapy and has the potential to improve outcomes for patients with lung metastasis.",

keywords = "CRC lung metastasis, Colorectal cancer, Nanoparticle therapeutics, PI3K inhibitors, Polymeric nanoparticles",

author = "Piotr Rychahou and Younsoo Bae and Derek Reichel and Zaytseva, {Yekaterina Y.} and Lee, {Eun Y.} and Dana Napier and Weiss, {Heidi L.} and Nick Roller and Heather Frohman and Le, {Anh Thu} and {Mark Evers}, B.",

note = "Funding Information: The authors thank the Markey Cancer Center's Research Communications Office for help with manuscript preparation. We also thank the Biostatistics and Bioinformatics and the Biospecimen Procurement and Translational Pathology Shared Resource Facilities of the Markey Cancer Center for statistical analysis and histologic assessment, respectively. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the grant funding agencies. This study was supported by grants P30 CA177558 , R01 CA195573 , and R01 DK048498 from the National Institutes of Health (NIH). Publisher Copyright: {\textcopyright} 2018 The Authors",

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AU - Bae, Younsoo

AU - Reichel, Derek

AU - Zaytseva, Yekaterina Y.

AU - Lee, Eun Y.

AU - Napier, Dana

AU - Weiss, Heidi L.

AU - Roller, Nick

AU - Frohman, Heather

AU - Le, Anh Thu

AU - Mark Evers, B.

N1 - Funding Information: The authors thank the Markey Cancer Center's Research Communications Office for help with manuscript preparation. We also thank the Biostatistics and Bioinformatics and the Biospecimen Procurement and Translational Pathology Shared Resource Facilities of the Markey Cancer Center for statistical analysis and histologic assessment, respectively. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the grant funding agencies. This study was supported by grants P30 CA177558 , R01 CA195573 , and R01 DK048498 from the National Institutes of Health (NIH). Publisher Copyright: © 2018 The Authors

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N2 - Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States; the predominant cause for mortality is metastasis to distant organs (e.g., lung). A major problem limiting the success of chemotherapy in metastatic CRC is the inability to target tumor tissues selectively and avoid severe side effects to normal tissues and organs. Here, we demonstrate polymeric nanoparticles (PNPs) entrapping chemotherapeutic agents provide a new therapeutic option for treating CRC that has metastasized to the lung. PNPs assembled from FDA approved biocompatible block copolymer accumulated predominantly in lung tissue. PNPs showed negligible accumulation in liver, spleen and kidneys, which was confirmed by fluorescent nanoparticle imaging and analysis of PI3K inhibition in the organs. PNPs entrapping PI3K inhibitors (i.e., wortmannin and PX866) suppressed CRC lung metastasis growth, and SN-38-loaded PNPs completely eliminated CRC lung metastasis. Our results demonstrate that polymer-drug nanoparticles offer a new approach to reduce toxicity of cancer therapy and has the potential to improve outcomes for patients with lung metastasis.

AB - Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States; the predominant cause for mortality is metastasis to distant organs (e.g., lung). A major problem limiting the success of chemotherapy in metastatic CRC is the inability to target tumor tissues selectively and avoid severe side effects to normal tissues and organs. Here, we demonstrate polymeric nanoparticles (PNPs) entrapping chemotherapeutic agents provide a new therapeutic option for treating CRC that has metastasized to the lung. PNPs assembled from FDA approved biocompatible block copolymer accumulated predominantly in lung tissue. PNPs showed negligible accumulation in liver, spleen and kidneys, which was confirmed by fluorescent nanoparticle imaging and analysis of PI3K inhibition in the organs. PNPs entrapping PI3K inhibitors (i.e., wortmannin and PX866) suppressed CRC lung metastasis growth, and SN-38-loaded PNPs completely eliminated CRC lung metastasis. Our results demonstrate that polymer-drug nanoparticles offer a new approach to reduce toxicity of cancer therapy and has the potential to improve outcomes for patients with lung metastasis.

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Colorectal cancer lung metastasis treatment with polymer–drug nanoparticles

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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