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.

抗癌剂的局部给药有可能最大限度地提高治疗效果并最大限度地减少急性和长期全身毒性。在这里，我们通过指数富集使用无监督的配体系统进化来鉴定四种 RNA 适体，它们特异性识别浸润肿瘤的小鼠和人类骨髓细胞，但在多种小鼠模型和头颈部鳞状细胞癌 (HNSCC) 患者中不识别它们的外周或循环对应物。 ）。使用这些与多柔比星缀合的适体增强了化疗药物在乳腺和纤维肉瘤小鼠模型中原发性和转移性肿瘤部位的积累和旁观者释放。在 4T1 乳腺癌模型中，这些多柔比星缀合的适体优于 Doxil，第一个临床批准的用于靶向化疗的高度优化的纳米颗粒，仅在 3 次给药后促进肿瘤消退，没有检测到体重减轻或血液化学变化。这些 RNA 适体识别体内各种小鼠肿瘤和离体人 HNSCC 中的肿瘤浸润性骨髓细胞。这项工作建议使用 RNA 适体检测人类骨髓来源的抑制细胞，并将化学疗法靶向递送至多种恶性肿瘤的肿瘤微环境。