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Cited by 37Nanoparticle-Based Drug DeliveryImmunotherapy and Immune ResponsesNanoplatforms for cancer theranostics

Boosting Interleukin‐12 Antitumor Activity and Synergism with Immunotherapy by Targeted Delivery with isoDGR‐Tagged Nanogold

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Gasparri, Anna Maria, Sacchi, Angelina, Basso, Veronica, Cortesi, Filippo, Freschi, Massimo, Rrapaj, Eltjona, Bellone, Matteo, Casorati, Giulia +4 more·2019·Small
DOI 10.1002/smll.201903462
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Abstract

The clinical use of interleukin‐12 (IL12), a cytokine endowed with potent immunotherapeutic anticancer activity, is limited by systemic toxicity. The hypothesis is addressed that gold nanoparticles tagged with a tumor‐homing peptide containing isoDGR, an αvβ3‐integrin binding motif, can be exploited for delivering IL12 to tumors and improving its therapeutic index. To this aim, gold nanospheres are functionalized with the head‐to‐tail cyclized‐peptide CGisoDGRG (Iso1) and murine IL12. The resulting nanodrug (Iso1/Au/IL12) is monodispersed, stable, and bifunctional in terms of αvβ3 and IL12‐receptor recognition. Low‐dose Iso1/Au/IL12, equivalent to 18–75 pg of IL12, induces antitumor effects in murine models of fibrosarcomas and mammary adenocarcinomas, with no evidence of toxicity. Equivalent doses of Au/IL12 (a nanodrug lacking Iso1) fail to delay tumor growth, whereas 15 000 pg of free IL12 is necessary to achieve similar effects. Iso1/Au/IL12 significantly increases tumor infiltration by innate immune cells, such as NK and iNKT cells, monocytes, and neutrophils. NK cell depletion completely inhibits its antitumor effects. Low‐dose Iso1/Au/IL12 can also increase the therapeutic efficacy of adoptive T‐cell therapy in mice with autochthonous prostate cancer. These findings indicate that coupling IL12 to isoDGR‐tagged nanogold is a valid strategy for enhancing its therapeutic index and sustaining adoptive T‐cell therapy.

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  • Gold nanoparticles labeled with tumor-homing peptide containing isoDGR can be targeted delivery of therapeutic agents to tumors and improve its therapeutic index.

    “Gold nanoparticles labeled with tumor-homing peptide containing isoDGR can be targeted delivery of therapeutic agents to tumors and improve its therapeutic index.90”

    From Smart nanoparticles for cancer therapy (2023) · cites this paper as [90]

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Authors
Gasparri, A. M., Sacchi, A., Basso, V., Cortesi, F., Freschi, M., Rrapaj, E., Bellone, M., Casorati, G., Dellabona, P., Mondino, A., Corti, A., & Curnis, F.
Affiliations
  • IRCCS Ospedale San Raffaele (IT)
  • Vita-Salute San Raffaele University (IT)
Corresponding author
  • Corti, Angelo
  • Curnis, Flavio
ORCID
Venue
Small
Publisher
Wiley
Published
2019-09-16
Volume
15
Issue
45
Pages
e1903462-e1903462
ISSN
  • 1613-6810 (ISSN-L)
  • 1613-6829
DOI
10.1002/smll.201903462
OpenAlex
W2974774350
Cited by
37
References
75
Citations by year
2026: 4 · 2025: 4 · 2024: 7 · 2023: 3 · 2022: 8 · 2021: 7 · 2020: 4
FWCI
1.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Small (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, cc-by-nc)
Funders
  • Ministero della Salute (RF‐2011‐02350836, RF‐2016‐02361054)
  • Associazione Italiana per la Ricerca sul Cancro (IG19220, 22737, IG15883)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
Keywords
IL-12, gold nanoparticles, integrin αvβ3, targeted drug delivery, nanotherapeutics, cancer immunotherapy, natural killer cells, invariant natural killer T cells, adoptive T cell therapy, prostate cancer, fibrosarcoma, mammary adenocarcinoma, cytokine toxicity, tumor microenvironment
MeSH terms
Adenocarcinoma, Animals, Cells, Cultured, Female, Fibrosarcoma, Gold, Immunotherapy, Male, Mammary Neoplasms, Animal, Interleukin-12, Mice, Metal Nanoparticles

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