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用于靶向多种肿瘤标志物的聚苹果酸基纳米生物聚合物:个性化医疗的契机?

Polymalic acid-based nano biopolymers for targeting of multiple tumor markers: an opportunity for personalized medicine?

作者信息

Ljubimova Julia Y, Ding Hui, Portilla-Arias Jose, Patil Rameshwar, Gangalum Pallavi R, Chesnokova Alexandra, Inoue Satoshi, Rekechenetskiy Arthur, Nassoura Tala, Black Keith L, Holler Eggehard

机构信息

Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center.

Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center;

出版信息

J Vis Exp. 2014 Jun 13(88):50668. doi: 10.3791/50668.

Abstract

Tumors with similar grade and morphology often respond differently to the same treatment because of variations in molecular profiling. To account for this diversity, personalized medicine is developed for silencing malignancy associated genes. Nano drugs fit these needs by targeting tumor and delivering antisense oligonucleotides for silencing of genes. As drugs for the treatment are often administered repeatedly, absence of toxicity and negligible immune response are desirable. In the example presented here, a nano medicine is synthesized from the biodegradable, non-toxic and non-immunogenic platform polymalic acid by controlled chemical ligation of antisense oligonucleotides and tumor targeting molecules. The synthesis and treatment is exemplified for human Her2-positive breast cancer using an experimental mouse model. The case can be translated towards synthesis and treatment of other tumors.

摘要

由于分子图谱的差异,具有相似分级和形态的肿瘤对相同治疗的反应往往不同。为了解决这种多样性问题,人们开发了个性化药物来沉默与恶性肿瘤相关的基因。纳米药物通过靶向肿瘤并递送反义寡核苷酸来沉默基因,从而满足这些需求。由于治疗药物通常需要反复给药,因此理想的情况是没有毒性且免疫反应可忽略不计。在这里给出的例子中,通过反义寡核苷酸和肿瘤靶向分子的可控化学连接,从可生物降解、无毒且无免疫原性的聚苹果酸平台合成了一种纳米药物。使用实验小鼠模型对人Her2阳性乳腺癌进行了合成和治疗的示例。该案例可推广到其他肿瘤的合成和治疗。

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