Aptamers against mouse and human tumor-infiltrating myeloid cells as reagents for targeted chemotherapy.
Aptamers against mouse and human tumor-infiltrating myeloid cells as reagents for targeted chemotherapy.
复制标题
抗小鼠和人肿瘤浸润性骨髓细胞适配体作为靶向化疗试剂。
DOI：
10.1126/scitranslmed.aav9760
复制
发表时间：
2020-06-17
影响因子：
17.1
通讯作者：
中科院分区：
文献类型：
--
作者：
局部递送抗癌剂具有最大化治疗功效和最小化急性和长期全身毒性的潜力。在这里，我们使用指数富集配体的无监督系统进化（SELEX）来鉴定四种RNA适体，它们特异性识别小鼠和人骨髓细胞浸润肿瘤，但在多种小鼠模型和头颈部鳞状细胞癌（HNSCC）患者中不识别其外周或循环对应物。使用这些与阿霉素缀合的适体增强了乳腺和纤维肉瘤小鼠模型中化疗药物在原发性和转移性肿瘤部位的蓄积和旁观者释放。在4T1乳腺癌模型中，这些多柔比星缀合的适体通过促进肿瘤消退而优于Doxil，Doxil是第一种临床上批准的高度优化的用于靶向化疗的纳米颗粒，在仅3次给药后没有检测到毒性，测量为体重减轻和血液化学。这些RNA适体在体内识别多种小鼠肿瘤中的肿瘤浸润骨髓细胞和离体识别来自人HNSCC的肿瘤浸润骨髓细胞。这表明它们可用于检测人类骨髓源性抑制细胞（MDSC），并用于将化疗靶向递送至多种恶性肿瘤的肿瘤微环境。特异性针对小鼠和人肿瘤浸润性骨髓细胞的适体允许在多种小鼠模型中将抗癌药物递送至肿瘤微环境。
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 (SELEX) 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, by promoting tumor regression with no detected toxicity measured as weight loss and by blood chemistry after just 3 administrations. These RNA aptamers recognized tumor infiltrating myeloid cells in a variety of mouse tumors in vivo and from human HNSCC ex vivo. This suggests their use for the detection of myeloid-derived suppressor cells (MDSCs) in human and for a targeted delivery of chemotherapy to the tumor microenvironment in multiple malignancies. Aptamers specific for mouse and human tumor-infiltrating myeloid cells allow delivery of anticancer drugs to the tumor microenvironment in multiple mouse models.
登录
查看更多内容
影响因子：
6.4
作者：
Erez, Neta;Coussens, Lisa M.
通讯作者：
Coussens, Lisa M.
影响因子：
7.3
作者：
Fleming V;Hu X;Weber R;Nagibin V;Groth C;Altevogt P;Utikal J;Umansky V
通讯作者：
Umansky V
影响因子：
4.7
作者：
Catuogno S;Esposito CL
通讯作者：
Esposito CL
影响因子：
16.6
作者：
Boye TL;Maeda K;Pezeshkian W;Sønder SL;Haeger SC;Gerke V;Simonsen AC;Nylandsted J
通讯作者：
Nylandsted J
影响因子：
5.4
作者：
Bulbake U;Doppalapudi S;Kommineni N;Khan W
通讯作者：
Khan W