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一种智能响应的双适体靶向气泡生成纳米系统用于癌症三联治疗和超声成像。

A Smart Responsive Dual Aptamers-Targeted Bubble-Generating Nanosystem for Cancer Triplex Therapy and Ultrasound Imaging.

机构信息

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China.

Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, 450001, China.

出版信息

Small. 2017 May;13(20). doi: 10.1002/smll.201603990. Epub 2017 Mar 30.

Abstract

The absence of targeted, single treatment methods produces low therapeutic value for treating cancers. To increase the accumulation of drugs in tumors and improve the treatment effectiveness, near-infrared 808 nm photothermal responsive dual aptamers-targeted docetaxel (DTX)-containing nanoparticles is proposed. In this system, DTX and NH HCO are loaded in thermosensitive liposomes. The surface of liposomes is coated with gold nanoshells and connected with sulfydryl (SH) modified AS1411 and S2.2 aptamers. The nanosystem has good biocompatibility and uniform size (diameter about 200 nm). The drug is rapidly released, reaching a maximum amount (84%) at 4 h under 808 nm laser irradiation. The experiments conducted in vitro and in vivo demonstrate the nanosystem can synergistically inhibit tumor growth by combination of chemotherapy, photothermal therapy, and biological therapy. Dual ligand functionalization significantly increases cellular uptake on breast cancer cell line (MCF-7) cells and achieves ultrasound imaging (USI) at tumor site. The results indicate that this drug delivery system is a promising theranostic agent involving light-thermal response at tumor sites, dual ligand targeted triplex therapy, and USI.

摘要

缺乏靶向单一治疗方法导致癌症治疗的疗效较低。为了增加肿瘤内药物的蓄积并提高治疗效果,提出了近红外 808nm 光热响应双适体靶向多西紫杉醇(DTX)载药纳米粒。在该系统中,DTX 和 NHHCO 装载于热敏脂质体中。脂质体的表面包覆金纳米壳,并连接巯基(SH)修饰的 AS1411 和 S2.2 适体。该纳米系统具有良好的生物相容性和均一的粒径(直径约 200nm)。在 808nm 激光照射下,药物迅速释放,在 4h 时达到最大释放量(84%)。体外和体内实验表明,该纳米系统通过化疗、光热治疗和生物治疗的协同作用,能有效地抑制肿瘤生长。双配体功能化显著增加了乳腺癌细胞系(MCF-7)细胞的摄取,并在肿瘤部位实现了超声成像(USI)。结果表明,该递药系统是一种很有前途的治疗药物,涉及肿瘤部位的光热响应、双配体靶向三联疗法和 USI。

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