Aptamers against mouse and human tumor-infiltrating myeloid cells as reagents for targeted chemotherapy

Adriana de la Fuente, Serena Zilio, Jimmy Caroli, Dimitri van Simaeys, Emilia M.C. Mazza, Tan A. Ince, Vincenzo Bronte, Silvio Bicciato, Donald T. Weed, Paolo Serafini

Research output: Contribution to journalArticle

Abstract

Local delivery of anticancer agents has the potential to maximize treatment efficacy and minimize the acute and long-term systemic toxicities. Here, we used unsupervised systematic evolution of ligands by exponential enrichment to identify four RNA aptamers that specifically recognized mouse and human myeloid cells infiltrating tumors but not their peripheral or circulating counterparts in multiple mouse models and from patients with head and neck squamous cell carcinoma (HNSCC). The use of these aptamers conjugated to doxorubicin enhanced the accumulation and bystander release of the chemotherapeutic drug in both primary and metastatic tumor sites in breast and fibrosarcoma mouse models. In the 4T1 mammary carcinoma model, these doxorubicin-conjugated aptamers outperformed Doxil, the first clinically approved highly optimized nanoparticle for targeted chemotherapy, promoting tumor regression after just three administrations with no detected changes in weight loss or blood chemistry. These RNA aptamers recognized tumor infiltrating myeloid cells in a variety of mouse tumors in vivo and from human HNSCC ex vivo. This work suggests the use of RNA aptamers for the detection of myeloid-derived suppressor cells in humans and for a targeted delivery of chemotherapy to the tumor microenvironment in multiple malignancies.

Original languageEnglish (US)
Article numbereaav9760
JournalScience Translational Medicine
Volume12
Issue number548
DOIs
StatePublished - Jun 17 2020

ASJC Scopus subject areas

  • Medicine(all)

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