MiRNA10b-directed nanotherapy effectively targets brain metastases from breast cancer.
MiRNA10b-directed nanotherapy effectively targets brain metastases from breast cancer.
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DOI：
10.1038/s41598-021-82528-2
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发表时间：
2021-02-02
影响因子：
4.6
通讯作者：
Medarova Z
中科院分区：
文献类型：
--
作者：
Yoo B;Ross A;Pantazopoulos P;Medarova Z
RNA干扰由于其效力、多功能性和模块性而代表了最吸引人的癌症治疗方式之一。由于该机制是催化性的，并且在转录后水平上影响致病抗原的表达，因此仅需要将少量的治疗剂递送至靶标以发挥稳健的治疗效果。RNA干扰也优于其他治疗方式，如单克隆抗体或小分子，因为它具有更广泛的药物靶点。最后，遗传密码的互补性使我们有机会使用计算的，理性的方法来设计RNAi疗法。之前，我们开发并测试了一种RNAi靶向治疗剂，称为MN-抗miR 10 b，其设计用于抑制转移和转移定植的关键驱动因素miRNA-10 b。我们在转移性乳腺癌的动物模型中显示，在简单的静脉注射后，MN-抗miR 10 b积聚到淋巴结、肺和骨中的肿瘤和转移中。我们还发现，结合MN-抗miR 10 b的治疗有效抑制转移瘤的出现，并且可以使淋巴结、肺和骨中已经建立的转移瘤消退。在本研究中，我们将MN-抗miR 10 b的应用扩展到乳腺癌脑转移模型。我们证明了转移病灶的递送，并获得了表现为抑制转移进展的治疗效果的证据。这项研究代表了将类似的RNAi靶向疗法转化为全身治疗转移性疾病的另一个步骤。
RNA interference represents one of the most appealing therapeutic modalities for cancer because of its potency, versatility, and modularity. Because the mechanism is catalytic and affects the expression of disease-causing antigens at the post-transcriptional level, only small amounts of therapeutic need to be delivered to the target in order to exert a robust therapeutic effect. RNA interference is also advantageous over other treatment modalities, such as monoclonal antibodies or small molecules, because it has a much broader array of druggable targets. Finally, the complementarity of the genetic code gives us the opportunity to design RNAi therapeutics using computational, rational approaches. Previously, we developed and tested an RNAi-targeted therapeutic, termed MN-anti-miR10b, which was designed to inhibit the critical driver of metastasis and metastatic colonization, miRNA-10b. We showed in animal models of metastatic breast cancer that MN-anti-miR10b accumulated into tumors and metastases in the lymph nodes, lungs, and bone, following simple intravenous injection. We also found that treatment incorporating MN-anti-miR10b was effective at inhibiting the emergence of metastases and could regress already established metastases in the lymph nodes, lungs, and bone. In the present study, we extend the application of MN-anti-miR10b to a model of breast cancer metastatic to the brain. We demonstrate delivery to the metastatic lesions and obtain evidence of a therapeutic effect manifested as inhibition of metastatic progression. This investigation represents an additional step towards translating similar RNAi-targeted therapeutics for the systemic treatment of metastatic disease.
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将miR-10b靶向的纳米疗法与低剂量阿霉素结合起来，引起转移性乳腺癌的持久回归。
影响因子：
11.2
作者：
Yoo B;Kavishwar A;Ross A;Wang P;Tabassum DP;Polyak K;Barteneva N;Petkova V;Pantazopoulos P;Tena A;Moore A;Medarova Z
通讯作者：
Medarova Z
影响因子：
46.9
作者：
Ma L;Reinhardt F;Pan E;Soutschek J;Bhat B;Marcusson EG;Teruya-Feldstein J;Bell GW;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
11.2
作者：
Kumar M;Yigit M;Dai G;Moore A;Medarova Z
通讯作者：
Medarova Z
影响因子：
3.7
作者：
Salvalaio M;Rigon L;Belletti D;D'Avanzo F;Pederzoli F;Ruozi B;Marin O;Vandelli MA;Forni F;Scarpa M;Tomanin R;Tosi G
通讯作者：
Tosi G
影响因子：
4.6
作者：
Yoo B;Kavishwar A;Wang P;Ross A;Pantazopoulos P;Dudley M;Moore A;Medarova Z
通讯作者：
Medarova Z