BACKGROUND Nanomedicine is a promising new approach to cancer treatment that avoids the disadvantages of traditional chemotherapy and improves therapeutic indices. However, the lack of a real-time visualization imaging technology to monitor drug distribution greatly limits its clinical application. Image-tracked drug delivery is of great clinical interest; it is useful for identifying those patients for whom the therapy is more likely to be beneficial. This paper discusses a novel nanomedicine that displays features of nanoparticles and facilitates functional magnetic resonance imaging but is challenging to prepare. RESULTS To achieve this goal, we synthesized an acylamino-containing amphiphilic block copolymer (polyethylene glycol-polyacrylamide-polyacetonitrile, PEG-b-P(AM-co-AN)) by reversible addition-fragmentation chain transfer (RAFT) polymerization. The PEG-b-P(AM-co-AN) has chemical exchange saturation transfer (CEST) effects, which enable the use of CEST imaging for monitoring nanocarrier accumulation and providing molecular information of pathological tissues. Based on PEG-b-P(AM-co-AN), a new nanomedicine PEG-PAM-PAN@DOX was constructed by nano-precipitation. The self-assembling nature of PEG-PAM-PAN@DOX made the synthesis effective, straightforward, and biocompatible. In vitro studies demonstrate decreased cytotoxicity of PEG-PAM-PAN@DOX compared to free doxorubicin (half-maximal inhibitory concentration (IC50), mean ~ 0.62 μg/mL vs. ~ 5 μg/mL), and the nanomedicine more efficiently entered the cytoplasm and nucleus of cancer cells to kill them. Further, in vivo animal experiments showed that the nanomedicine developed was not only effective against breast cancer, but also displayed an excellent sensitive CEST effect for monitoring drug accumulation (at about 0.5 ppm) in tumor areas. The CEST signal of post-injection 2 h was significantly higher than that of pre-injection (2.17 ± 0.88% vs. 0. 09 ± 0.75%, p < 0.01). CONCLUSIONS The nanomedicine with CEST imaging reflects the characterization of tumors and therapeutic functions has great potential medical applications.

中文翻译：

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具有化学交换饱和转移作用的新型纳米药物，可用于体内乳腺癌治疗。

背景技术纳米医学是一种有前途的新的癌症治疗方法，其避免了传统化学疗法的缺点并提高了治疗指标。然而，缺乏实时可视化成像技术来监测药物分布极大地限制了其临床应用。图像跟踪的药物输送具有重大的临床意义；这对于确定那些对治疗更有可能受益的患者很有用。本文讨论了一种新型的纳米药物，它可以显示纳米颗粒的特征并促进功能性磁共振成像，但制备难度很大。结果为了实现这一目标，我们合成了一种含酰基氨基的两亲嵌段共聚物（聚乙二醇-聚丙烯酰胺-聚乙腈，PEG-bP（AM-co-AN））可逆加成-断裂链转移（RAFT）聚合。PEG-bP（AM-co-AN）具有化学交换饱和转移（CEST）的作用，使CEST成像可用于监测纳米载体的积累并提供病理组织的分子信息。基于PEG-bP（AM-co-AN），通过纳米沉淀法构建了一种新的纳米药物PEG-PAM-PAN @ DOX。PEG-PAM-PAN @ DOX的自组装性质使合成有效，简单且具有生物相容性。体外研究表明，与游离阿霉素相比，PEG-PAM-PAN @ DOX的细胞毒性降低了（半数最大抑制浓度（IC50），平均〜0.62μg/ mL对〜5μg/ mL），并且纳米药物更有效地进入了癌细胞的胞质和细胞核可以杀死它们。进一步，体内动物实验表明，开发的纳米药物不仅对乳腺癌有效，而且对监测肿瘤区域中的药物蓄积（约0.5 ppm）表现出出色的敏感CEST效果。注射后2 h的CEST信号明显高于注射前（2.17±0.88％vs. 0. 09±0.75％，p <0.01）。结论带有CEST成像的纳米药物反映了肿瘤的特征，治疗功能具有巨大的潜在医学应用。