pH/GSH Dual-Responsive Janus-Type Au@H-MP@DOX MR Molecular Imaging Nanomotor for Combined Photothermal/Chemotherapeutic Treatment of Pancreatic Cancer.

IF 4.5 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Hao Zhang, Dan Xie, Meng Chen, Qiangqiang Yin, Guangyue Shi, Jialong He, Xiaoyang Yu, Qian Lu, Zhengji Wang, Jing Dong, Liguo Hao
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Abstract

Chemotherapy is a widely used cancer treatment modality, while the complex tumor microenvironment (TME) significantly impedes drug delivery and deep tissue penetration. An MR molecular imaging drug-loaded nanomotor has been developed to achieve deep tumor tissue penetration and imaging-guided drug delivery, enabling combined photothermal and chemotherapeutic treatment of pancreatic cancer. A Janus-type nanomotor (Au@H-MP NMs) was fabricated via magnetron sputtering for application in photothermal therapy. Doxorubicin (DOX) was loaded onto one hemisphere of the nanomotor, achieving combined photothermal and chemotherapeutic treatment. Additionally, the nanomotor exhibits dual responsiveness to pH and glutathione (GSH), facilitating the controlled release of DOX within deep tumor tissues. Studies confirmed the nanomotors excellent biosafety, strong photothermal conversion capability, and effective induction of apoptosis. Tumor tissue penetration was validated through in vitro migration and infiltration assays, while in vivo experiments demonstrated significant tumor suppression and enhanced drug accumulation. Moreover, MR imaging technology enables real-time monitoring of nanomotor dynamics. These findings suggest that the synthesized Janus-type MR molecular imaging nanomotor offers a promising strategy for multimodal treatment of pancreatic cancer with significant clinical potential.

pH/GSH双响应janus型Au@H-MP@DOX MR分子成像纳米马达用于光热/化疗联合治疗胰腺癌。
化疗是一种广泛使用的癌症治疗方式,而复杂的肿瘤微环境(TME)严重阻碍了药物的传递和深层组织渗透。一种磁共振分子成像载药纳米马达已被开发出来,可实现肿瘤组织深度穿透和成像引导药物递送,使光热和化疗联合治疗胰腺癌成为可能。采用磁控溅射法制备了janus型纳米马达(Au@H-MP NMs),用于光热治疗。将多柔比星(DOX)加载到纳米马达的一个半球上,实现光热和化疗的联合治疗。此外,纳米马达对pH和谷胱甘肽(GSH)具有双重响应性,促进DOX在深部肿瘤组织内的可控释放。研究证实纳米马达具有良好的生物安全性、较强的光热转化能力和诱导细胞凋亡的效果。通过体外迁移和浸润实验验证了肿瘤组织的渗透,而体内实验显示了显著的肿瘤抑制和增强药物积累。此外,核磁共振成像技术能够实时监测纳米运动动力学。这些结果表明,合成的janus型磁共振分子成像纳米马达为胰腺癌的多模式治疗提供了一种有希望的策略,具有重要的临床潜力。
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来源期刊
Molecular Pharmaceutics
Molecular Pharmaceutics 医学-药学
CiteScore
8.00
自引率
6.10%
发文量
391
审稿时长
2 months
期刊介绍: Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development. Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.
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