Spherical Nucleic Acids as Precision Therapeutics for the Treatment of Cancer-From Bench to Bedside.
Spherical Nucleic Acids as Precision Therapeutics for the Treatment of Cancer-From Bench to Bedside.
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DOI：
10.3390/cancers14071615
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发表时间：
2022-03-23
期刊：
影响因子：
5.2
通讯作者：
Stegh AH
中科院分区：
文献类型：
--
作者：
Mahajan AS;Stegh AH
纳米技术使诊断和治疗癌症的新方法成为可能。与“游离”形式的药物相比，纳米药物可以增加疾病部位的有效载荷浓度，降低毒性并增强治疗效果。球形核酸（SNA）作为一类新的寡核苷酸纳米治疗剂出现，目前正在探索作为基因调控和免疫刺激架构，以克服实体瘤中的耐药性和免疫抑制。这篇综述强调了开创性的研究，这些研究将SNA确定为基因调控，先天免疫激活和下一代癌症疫苗开发的强大平台，讨论了最近将实验室的基本发现转化为临床的努力，并对未来的研究进行了展望，旨在利用SNA平台的全部治疗潜力。球形核酸（SNA）作为一类新的纳米治疗剂出现，其由用径向定向的合成寡核苷酸的壳密集官能化的纳米颗粒核组成。SNA的独特三维结构保护寡核苷酸免受核酸酶介导的降解，增加寡核苷酸生物利用度，并且在不存在辅助转染剂的情况下，通过与细胞表面模式识别受体的多价缔合，使其能够被稳健地摄取到肿瘤和免疫细胞中。当由基因调节性小干扰（si）RNA或免疫刺激性DNA或RNA寡核苷酸组成时，SNA沉默基因表达并诱导比由其“游离”形式的寡核苷酸引起的免疫应答更上级的免疫应答。在胶质母细胞瘤中基于基因调节siRNA的SNA（NCT 03020017）和在实体瘤中携带未甲基化的富含CpG的寡核苷酸的免疫刺激性Toll样受体9（TLR9）激动性SNA（NCT 03086278）的早期临床试验表明，SNA代表用于抑制癌基因表达和刺激针对肿瘤的免疫应答的安全的脑渗透疗法。本文综述了SNA作为精确癌症治疗剂的应用，总结了SNA在实体瘤中首次人体临床试验的结果，描述了合理设计下一代多模式SNA架构的最新临床前工作，并对未来最大限度地提高SNA平台抗肿瘤活性的努力进行了展望。
Nanotechnology enables new ways to diagnose and treat cancer. Nanomedicines can increase payload concentration at the disease site, reduce toxicity, and enhance therapeutic effects compared to drugs in their “free” form. Spherical Nucleic Acids (SNAs) emerged as a new class of oligonucleotide nanotherapeutics that are currently being explored as gene-regulatory and immunostimulatory architectures to overcome drug resistance and immunosuppression in solid tumors. This review highlights seminal studies that identified SNAs as a powerful platform for gene regulation, the activation of innate immunity, and the development of next-generation cancer vaccines, discusses recent efforts to translate fundamental discovery from the laboratory into the clinic, and provides an outlook on future research aimed at harnessing the full therapeutic potential of the SNA platform. Spherical Nucleic Acids (SNAs) emerged as a new class of nanotherapeutics consisting of a nanoparticle core densely functionalized with a shell of radially oriented synthetic oligonucleotides. The unique three-dimensional architecture of SNAs protects the oligonucleotides from nuclease-mediated degradation, increases oligonucleotide bioavailability, and in the absence of auxiliary transfection agents, enables robust uptake into tumor and immune cells through polyvalent association with cell surface pattern recognition receptors. When composed of gene-regulatory small interfering (si)RNA or immunostimulatory DNA or RNA oligonucleotides, SNAs silence gene expression and induce immune responses superior to those raised by the oligonucleotides in their “free” form. Early phase clinical trials of gene-regulatory siRNA-based SNAs in glioblastoma (NCT03020017) and immunostimulatory Toll-like receptor 9 (TLR9)-agonistic SNAs carrying unmethylated CpG-rich oligonucleotides in solid tumors (NCT03086278) have shown that SNAs represent a safe, brain-penetrant therapy for inhibiting oncogene expression and stimulating immune responses against tumors. This review focuses on the application of SNAs as precision cancer therapeutics, summarizes the findings from first-in-human clinical trials of SNAs in solid tumors, describes the most recent preclinical efforts to rationally design next-generation multimodal SNA architectures, and provides an outlook on future efforts to maximize the anti-neoplastic activity of the SNA platform.
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影响因子：
18.2
作者：
Callmann CE;Kusmierz CD;Dittmar JW;Broger L;Mirkin CA
通讯作者：
Mirkin CA
影响因子：
15
作者：
Banga RJ;Meckes B;Narayan SP;Sprangers AJ;Nguyen ST;Mirkin CA
通讯作者：
Mirkin CA
DOI：
10.1073/pnas.2005794117
发表时间：
2020-07-28
影响因子：
11.1
作者：
Callmann, Cassandra E.;Cole, Lisa E.;Mirkin, Chad A.
通讯作者：
Mirkin, Chad A.
影响因子：
15
作者：
Brodin JD;Sprangers AJ;McMillan JR;Mirkin CA
通讯作者：
Mirkin CA
DOI：
10.1016/j.bbrc.2009.11.034
发表时间：
2010-01-01
影响因子：
3.1
作者：
Florou, Dimitra;Papadopoulos, Iordanis N.;Scorilas, Andreas
通讯作者：
Scorilas, Andreas