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Cited by 350Nanoparticle-Based Drug DeliveryRNA Interference and Gene DeliveryBacteriophages and microbial interactions

Cell-Specific Delivery of Diverse Cargos by Bacteriophage MS2 Virus-like Particles

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Ashley, Carlee E., Carnes, Eric C., Phillips, Genevieve K., Durfee, Paul N., Buley, Mekensey D., Lino, Christopher A., Padilla, David P., Phillips, Brandy +7 more·2011·ACS Nano
DOI 10.1021/nn201397zPMC PMC3144304
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Abstract

Virus-like particles (VLPs) of bacteriophage MS2 possess numerous features that make them well-suited for use in targeted delivery of therapeutic and imaging agents. MS2 VLPs can be rapidly produced in large quantities using in vivo or in vitro synthesis techniques. Their capsids can be modified in precise locations via genetic insertion or chemical conjugation, facilitating the multivalent display of targeting ligands. MS2 VLPs also self-assemble in the presence of nucleic acids to specifically encapsidate siRNA and RNA-modified cargos. Here we report the use of MS2 VLPs to selectively deliver nanoparticles, chemotherapeutic drugs, siRNA cocktails, and protein toxins to human hepatocellular carcinoma (HCC). MS2 VLPs modified with a peptide (SP94) that binds HCC exhibit a 10(4)-fold higher avidity for HCC than for hepatocytes, endothelial cells, monocytes, or lymphocytes and can deliver high concentrations of encapsidated cargo to the cytosol of HCC cells. SP94-targeted VLPs loaded with doxorubicin, cisplatin, and 5-fluorouracil selectively kill the HCC cell line, Hep3B, at drug concentrations <1 nM, while SP94-targeted VLPs that encapsidate a siRNA cocktail, which silences expression of cyclin family members, induce growth arrest and apoptosis of Hep3B at siRNA concentrations <150 pM. Impressively, MS2 VLPs, when loaded with ricin toxin A-chain (RTA) and modified to codisplay the SP94 targeting peptide and a histidine-rich fusogenic peptide (H5WYG) that promotes endosomal escape, kill virtually the entire population of Hep3B cells at an RTA concentration of 100 fM without affecting the viability of control cells. Our results demonstrate that MS2 VLPs, because of their tolerance of multivalent peptide display and their ability to specifically encapsidate a variety of chemically disparate cargos, induce selective cytotoxicity of cancer in vitro and represent a significant improvement in the characteristics of VLP-based delivery systems.

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  • MS2 virus-like particles have been used as modular carriers for RNA therapeutics and peptide antigens, enabling efficient cargo encapsulation and robust activation of tumor-specific immune responses in proof-of-concept studies.

    “Similarly, MS2 virus-like particles (VLPs) have been used as modular carriers for RNA therapeutics and peptide antigens, enabling efficient cargo encapsulation and robust activation of tumor-specific immune responses in proof-of-concept studies [96]”

    From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [96]

    The Results section (page unavailable) reports encapsidation of siRNA and other cargos, with nearly 100% of fully assembled drug-, siRNA-, or ricin-loaded VLPs containing cargo. The paper describes SP94 as a peptide for targeting hepatocellular carcinoma cells, not a peptide antigen, and reports selective cancer-cell killing rather than activation of tumor-specific immune responses. (LLM, conf=0.91)

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Authors
Ashley, C. E., Carnes, E. C., Phillips, G. K., Durfee, P. N., Buley, M. D., Lino, C. A., Padilla, D. P., Phillips, B., Carter, M. B., Willman, C. L., Brinker, C. J., Caldeira, J. D. C., Chackerian, B., Wharton, W., & Peabody, D. S.
Affiliations
  • University of New Mexico (US)
  • University of Oklahoma (US)
  • Department of Molecular Genetics and Microbiology, the University of New Mexico, Albuquerque, New Mexico 87131, United States
Corresponding author
Ashley, Carlee E.
ORCID
Venue
ACS Nano
Publisher
American Chemical Society (ACS)
Published
2011-06-07
Volume
5
Issue
7
Pages
5729-5745
ISSN
  • 1936-0851 (ISSN-L)
  • 1936-086X
DOI
10.1021/nn201397z
PMC
PMC3144304
OpenAlex
W2075415955
Cited by
350
References
1
Citations by year
2026: 19 · 2025: 28 · 2024: 20 · 2023: 29 · 2022: 34 · 2021: 32 · 2020: 28 · 2019: 24 · 2018: 24 · 2017: 19 · 2016: 22 · 2015: 14 · 2014: 27 · 2013: 13 · 2012: 15
FWCI
7.48
Type
journal article
Language
en
Open access
Locations
  • ACS Nano (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Eye Institute (PN2EY016570, 2 PN2 EY016570B)
  • National Cancer Institute (U01CA151792)
  • National Institute of General Medical Sciences (R01 GM42901, R01GM042901)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
Keywords
bacteriophage MS2, virus-like particles, targeted drug delivery, hepatocellular carcinoma, peptide targeting, ricin toxin A chain, chemotherapy delivery, endosomal escape, apoptosis, nanoparticle delivery, Hep3B cells
MeSH terms
Amino Acid Sequence, Drug Carriers, Endocytosis, Humans, Molecular Sequence Data, Peptides, Ricin, RNA, Viral, Cyclins, Apoptosis, Levivirus, RNA, Small Interfering, Capsid Proteins, Cell Line, Tumor, Cell Proliferation

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