Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors

Granot-Matok, Yasmin; Ezra, Assaf; Ramishetti, Srinivas; Sharma, Preeti; Naidu, Gonna Somu; Benhar, Itai; Peer, Dan

doi:10.7150/thno.82228

Nanotheranostics

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International Journal of Medical Sciences

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Theranostics 2023; 13(11):3497-3508. doi:10.7150/thno.82228 This issue Cite

Research Paper

Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors

Yasmin Granot-Matok^1,2,3,4, Assaf Ezra^1,2,3,4, Srinivas Ramishetti^1,2,3,4, Preeti Sharma^1,2,3,4, Gonna Somu Naidu^1,2,3,4, Itai Benhar^2,4,5, Dan Peer^1,2,3,4,✉

1. Laboratory of Precision NanoMedicine, Shmunis School for Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
2. Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv 69978, Israel.
3. Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel.
4. Cancer Biology Research Center, Tel Aviv University, Tel Aviv 69978, Israel.
5. Laboratory of Antibody Engineering, Shmunis School for Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.

Citation:

Granot-Matok Y, Ezra A, Ramishetti S, Sharma P, Naidu GS, Benhar I, Peer D. Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors. Theranostics 2023; 13(11):3497-3508. doi:10.7150/thno.82228. https://www.thno.org/v13p3497.htm

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Abstract

Background and rationale: Cancer therapy have evolved remarkably over the past decade, providing new strategies to inhibit cancer cell growth using immune modulation, with or without gene therapy. Specifically, suicide gene therapies and immunotoxins have been investigated for the treatment of tumors by direct cancer cell cytotoxicity. Recent advances in mRNA delivery also demonstrated the potential of mRNA-based vaccines and immune-modulators for cancer therapeutics by utilizing nanocarriers for mRNA delivery.

Methods: We designed a bacterial toxin-encoding modified mRNA, delivered by lipid nanoparticles into a B16-melanoma mouse model.

Results: We showed that local administration of LNPs entrapping a modified mRNA that encodes for a bacterial toxin, induced significant anti-tumor effects and improved overall survival of treated mice.

Conclusions: We propose mmRNA-loaded LNPs as a new class of anti-tumoral, toxin-based therapy.

Keywords: lipid nanoparticles, mRNA, cancer therapy, gene therapy, suicide-gene therapy, immunotoxins

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APA

Granot-Matok, Y., Ezra, A., Ramishetti, S., Sharma, P., Naidu, G.S., Benhar, I., Peer, D. (2023). Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors. Theranostics, 13(11), 3497-3508. https://doi.org/10.7150/thno.82228.

ACS

Granot-Matok, Y.; Ezra, A.; Ramishetti, S.; Sharma, P.; Naidu, G.S.; Benhar, I.; Peer, D. Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors. Theranostics 2023, 13 (11), 3497-3508. DOI: 10.7150/thno.82228.

NLM

CSE

Granot-Matok Y, Ezra A, Ramishetti S, Sharma P, Naidu GS, Benhar I, Peer D. 2023. Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors. Theranostics. 13(11):3497-3508.

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