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Chemo hitches a ride
Anticancer agents such as chemotherapy are widely used; however, their efficacy and safety are hampered by off-target effects in surrounding healthy cells and tissues. To improve anticancer drug delivery, De La Fuente et al. identified four RNA aptamers that specifically recognized mouse and human myeloid cells infiltrating head and neck squamous cell carcinoma (HNSCC). Conjugating chemotherapeutic agent doxorubicin to these aptamers allowed drug delivery to the local tumor microenvironment in mouse models of breast cancer and fibrosarcoma via tumor-infiltrating myeloid cells and increased survival over the unmodified drug. This preclinical study suggests that RNA aptamers are a candidate approach to target drugs to tumors in humans.
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.
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