iRGD-Liposomes Enhance Tumor Delivery and Therapeutic Efficacy of Antisense Oligonucleotide Drugs against Primary Prostate Cancer and Bone Metastasis

JIBIN GUAN, Hong Guo, Tang Tang, Yihan Wang, Yushuang Wei, Punit Seth, Yingming Li, Scott M. Dehm, Erkki Ruoslahti, Hong Bo Pang

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13 Scopus citations


Nucleotide-based drugs, such as antisense oligonucleotides (ASOs), have unique advantages in treating human diseases as they provide virtually unlimited ability to target any gene. However, their clinical translation faces many challenges, one of which is poor delivery to the target tissue in vivo. This problem is particularly evident in solid tumors. Here, we functionalized liposomes with a tumor-homing and -penetrating peptide, iRGD, as a carrier of an ASO against androgen receptor (AR) for prostate cancer treatment. The iRGD-liposomes exhibited a high loading efficiency of AR-ASO, and an efficient knockdown of AR gene products was achieved in vitro, including AR splice variants. In vivo, iRGD-liposomes significantly increased AR-ASO accumulation in the tumor tissue and decreased AR expression relative to free ASOs in prostate tumors established as subcutaneous xenografts. Similar results were obtained with intra-tibial xenografts modeling metastasis to bones, the predominant site of metastasis for prostate cancer. In treatment studies, iRGD-liposomes markedly improved the AR-ASO efficacy in suppressing the growth of both subcutaneous xenografts and intra-tibial xenografts. The inhibitory effect on tumor growth was also significantly prolonged by the delivery of the AR-ASO in the iRGD-liposomes. Meanwhile, iRGD-liposomes did not increase ASO accumulation or toxicity in healthy organs. Overall, we provide here a delivery system that can significantly increase ASO accumulation and efficacy in solid tumors. These benefits are achieved without significant side effects, providing a way to increase the antitumor efficacy of ASOs.

Original languageEnglish (US)
Article number2100478
JournalAdvanced Functional Materials
Issue number24
StatePublished - Jun 9 2021

Bibliographical note

Funding Information:
The authors thank Dr. Michael J. Sailor, Dr. Aaron LeBeau, Dr. William Elmquist, Dr. Stephen Hecht, and Dr. Yupeng Li for their kind help on reagents and instrument. Research reported in this publication was supported by grants from the National Institute of Health (R01CA214550, R01GM133885, R21EB022652) and the State of Minnesota (MNP#19.08). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nanotechnology Coordinated Infrastructure (NNCI) under Award Number ECCS‐2025124.

Publisher Copyright:
© 2021 Wiley-VCH GmbH


  • antisense oligonucleotides
  • bone metastasis
  • cancer therapies
  • iRGD-liposomes
  • primary prostate cancer

PubMed: MeSH publication types

  • Journal Article


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