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Updated: Dec 18, 2025
A Flow Cytometry-Based Cell Surface Protein Binding Assay for Assessing Selectivity and Specificity of an Anticancer Aptamer
Published on: September 13, 2022
Aptamers against mouse and human tumor-infiltrating myeloid cells as reagents for targeted chemotherapy
Adriana De La Fuente1, Serena Zilio1, Jimmy Caroli2
1Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
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.
Insights
Researchers developed RNA aptamers for targeted cancer therapy. These aptamers deliver chemotherapy directly to tumor-infiltrating myeloid cells, outperforming current treatments and showing potential for detecting myeloid-derived suppressor cells.
Area of Science:
- Biotechnology
- Oncology
- Molecular Biology
Background:
- Local delivery of anticancer agents can improve efficacy and reduce systemic toxicity.
- Targeting tumor-infiltrating myeloid cells is a strategy to enhance cancer treatment.
Purpose of the Study:
- To identify RNA aptamers that specifically bind to tumor-infiltrating myeloid cells.
- To evaluate the efficacy of doxorubicin-conjugated aptamers for targeted cancer therapy.
Main Methods:
- Systematic evolution of ligands by exponential enrichment (SELEX) was used to discover RNA aptamers.
- Aptamers were conjugated to doxorubicin for drug delivery.
- Efficacy was tested in mouse models of breast and fibrosarcoma, and human head and neck squamous cell carcinoma (HNSCC).
Main Results:
- Four RNA aptamers were identified that specifically recognize myeloid cells in tumors, not in circulation.
- Doxorubicin-conjugated aptamers enhanced drug accumulation and bystander release at tumor sites.
- In the 4T1 mammary carcinoma model, aptamer treatment promoted tumor regression more effectively than Doxil, with no adverse effects.
Conclusions:
- RNA aptamers can be developed for targeted delivery of chemotherapy to the tumor microenvironment.
- These aptamers show potential for detecting myeloid-derived suppressor cells in humans.
- This approach offers a promising strategy for treating multiple malignancies with reduced toxicity.
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