In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases

Go Oshima, Nining Guo, Chunbai He, Melinda E. Stack, Christopher Poon, Abhineet Uppal, Sean C. Wightman, Akash Parekh, Kinga B. Skowron, Mitchell C. Posner, Wenbin Lin, Nikolai N. Khodarev, Ralph R. Weichselbaum

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Multiple therapeutic agents are typically used in concert to effectively control metastatic tumors. Recently, we described microRNAs that are associated with the oligometastatic state, in which a limited number of metastatic tumors progress to more favorable outcomes. Here, we report the effective delivery of an oligometastatic microRNA (miR-655-3p) to colorectal liver metastases using nanoscale coordination polymers (NCPs). The NCPs demonstrated a targeted and prolonged distribution of microRNAs to metastatic liver tumors. Tumor-targeted microRNA miR-655-3p suppressed tumor growth when co-delivered with oxaliplatin, suggesting additive or synergistic interactions between microRNAs and platinum drugs. This is the first known example of systemically administered nanoparticles delivering an oligometastatic microRNA to advanced metastatic liver tumors and demonstrating tumor-suppressive effects. Our results suggest a potential therapeutic strategy for metastatic liver disease by the co-delivery of microRNAs and conventional cytotoxic agents using tumor-specific NCPs. Oshima et al. describe nanoscale coordination polymers (NCPs) with oxaliplatin and metastases-suppressive miR-655-3p detected in oligometastatic patients. Designed NCPs suppressed colorectal liver metastases in preclinical models. Results suggest a therapeutic strategy for metastatic liver disease by the co-delivery of oligometastatic microRNAs and conventional drugs using tumor-specific NCPs.

Original languageEnglish
JournalMolecular Therapy
DOIs
Publication statusAccepted/In press - 2017 Feb 6
Externally publishedYes

Fingerprint

Therapeutic Uses
MicroRNAs
Neoplasm Metastasis
Liver
Polymers
oxaliplatin
Neoplasms
Liver Diseases
Cytotoxins
Platinum
Pharmaceutical Preparations
Nanoparticles
Therapeutics
Growth

Keywords

  • Colorectal cancer
  • Liver
  • Metastases
  • MicroRNA
  • Nanoparticles

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases. / Oshima, Go; Guo, Nining; He, Chunbai; Stack, Melinda E.; Poon, Christopher; Uppal, Abhineet; Wightman, Sean C.; Parekh, Akash; Skowron, Kinga B.; Posner, Mitchell C.; Lin, Wenbin; Khodarev, Nikolai N.; Weichselbaum, Ralph R.

In: Molecular Therapy, 06.02.2017.

Research output: Contribution to journalArticle

Oshima, G, Guo, N, He, C, Stack, ME, Poon, C, Uppal, A, Wightman, SC, Parekh, A, Skowron, KB, Posner, MC, Lin, W, Khodarev, NN & Weichselbaum, RR 2017, 'In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases', Molecular Therapy. https://doi.org/10.1016/j.ymthe.2017.04.005
Oshima, Go ; Guo, Nining ; He, Chunbai ; Stack, Melinda E. ; Poon, Christopher ; Uppal, Abhineet ; Wightman, Sean C. ; Parekh, Akash ; Skowron, Kinga B. ; Posner, Mitchell C. ; Lin, Wenbin ; Khodarev, Nikolai N. ; Weichselbaum, Ralph R. / In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases. In: Molecular Therapy. 2017.
@article{fb2d636bceec426499ab87643d4987f3,
title = "In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases",
abstract = "Multiple therapeutic agents are typically used in concert to effectively control metastatic tumors. Recently, we described microRNAs that are associated with the oligometastatic state, in which a limited number of metastatic tumors progress to more favorable outcomes. Here, we report the effective delivery of an oligometastatic microRNA (miR-655-3p) to colorectal liver metastases using nanoscale coordination polymers (NCPs). The NCPs demonstrated a targeted and prolonged distribution of microRNAs to metastatic liver tumors. Tumor-targeted microRNA miR-655-3p suppressed tumor growth when co-delivered with oxaliplatin, suggesting additive or synergistic interactions between microRNAs and platinum drugs. This is the first known example of systemically administered nanoparticles delivering an oligometastatic microRNA to advanced metastatic liver tumors and demonstrating tumor-suppressive effects. Our results suggest a potential therapeutic strategy for metastatic liver disease by the co-delivery of microRNAs and conventional cytotoxic agents using tumor-specific NCPs. Oshima et al. describe nanoscale coordination polymers (NCPs) with oxaliplatin and metastases-suppressive miR-655-3p detected in oligometastatic patients. Designed NCPs suppressed colorectal liver metastases in preclinical models. Results suggest a therapeutic strategy for metastatic liver disease by the co-delivery of oligometastatic microRNAs and conventional drugs using tumor-specific NCPs.",
keywords = "Colorectal cancer, Liver, Metastases, MicroRNA, Nanoparticles",
author = "Go Oshima and Nining Guo and Chunbai He and Stack, {Melinda E.} and Christopher Poon and Abhineet Uppal and Wightman, {Sean C.} and Akash Parekh and Skowron, {Kinga B.} and Posner, {Mitchell C.} and Wenbin Lin and Khodarev, {Nikolai N.} and Weichselbaum, {Ralph R.}",
year = "2017",
month = "2",
day = "6",
doi = "10.1016/j.ymthe.2017.04.005",
language = "English",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - In Vivo Delivery and Therapeutic Effects of a MicroRNA on Colorectal Liver Metastases

AU - Oshima, Go

AU - Guo, Nining

AU - He, Chunbai

AU - Stack, Melinda E.

AU - Poon, Christopher

AU - Uppal, Abhineet

AU - Wightman, Sean C.

AU - Parekh, Akash

AU - Skowron, Kinga B.

AU - Posner, Mitchell C.

AU - Lin, Wenbin

AU - Khodarev, Nikolai N.

AU - Weichselbaum, Ralph R.

PY - 2017/2/6

Y1 - 2017/2/6

N2 - Multiple therapeutic agents are typically used in concert to effectively control metastatic tumors. Recently, we described microRNAs that are associated with the oligometastatic state, in which a limited number of metastatic tumors progress to more favorable outcomes. Here, we report the effective delivery of an oligometastatic microRNA (miR-655-3p) to colorectal liver metastases using nanoscale coordination polymers (NCPs). The NCPs demonstrated a targeted and prolonged distribution of microRNAs to metastatic liver tumors. Tumor-targeted microRNA miR-655-3p suppressed tumor growth when co-delivered with oxaliplatin, suggesting additive or synergistic interactions between microRNAs and platinum drugs. This is the first known example of systemically administered nanoparticles delivering an oligometastatic microRNA to advanced metastatic liver tumors and demonstrating tumor-suppressive effects. Our results suggest a potential therapeutic strategy for metastatic liver disease by the co-delivery of microRNAs and conventional cytotoxic agents using tumor-specific NCPs. Oshima et al. describe nanoscale coordination polymers (NCPs) with oxaliplatin and metastases-suppressive miR-655-3p detected in oligometastatic patients. Designed NCPs suppressed colorectal liver metastases in preclinical models. Results suggest a therapeutic strategy for metastatic liver disease by the co-delivery of oligometastatic microRNAs and conventional drugs using tumor-specific NCPs.

AB - Multiple therapeutic agents are typically used in concert to effectively control metastatic tumors. Recently, we described microRNAs that are associated with the oligometastatic state, in which a limited number of metastatic tumors progress to more favorable outcomes. Here, we report the effective delivery of an oligometastatic microRNA (miR-655-3p) to colorectal liver metastases using nanoscale coordination polymers (NCPs). The NCPs demonstrated a targeted and prolonged distribution of microRNAs to metastatic liver tumors. Tumor-targeted microRNA miR-655-3p suppressed tumor growth when co-delivered with oxaliplatin, suggesting additive or synergistic interactions between microRNAs and platinum drugs. This is the first known example of systemically administered nanoparticles delivering an oligometastatic microRNA to advanced metastatic liver tumors and demonstrating tumor-suppressive effects. Our results suggest a potential therapeutic strategy for metastatic liver disease by the co-delivery of microRNAs and conventional cytotoxic agents using tumor-specific NCPs. Oshima et al. describe nanoscale coordination polymers (NCPs) with oxaliplatin and metastases-suppressive miR-655-3p detected in oligometastatic patients. Designed NCPs suppressed colorectal liver metastases in preclinical models. Results suggest a therapeutic strategy for metastatic liver disease by the co-delivery of oligometastatic microRNAs and conventional drugs using tumor-specific NCPs.

KW - Colorectal cancer

KW - Liver

KW - Metastases

KW - MicroRNA

KW - Nanoparticles

UR - http://www.scopus.com/inward/record.url?scp=85018327041&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018327041&partnerID=8YFLogxK

U2 - 10.1016/j.ymthe.2017.04.005

DO - 10.1016/j.ymthe.2017.04.005

M3 - Article

JO - Molecular Therapy

JF - Molecular Therapy

SN - 1525-0016

ER -