MRI-guided liposomes for targeted tandem chemotherapy and therapeutic response prediction

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• 作者：Lili Ren¹ ; Shizhen Chen¹ ; Haidong Li ; Zhiying Zhang ; Jianping Zhong ; Maili Liu ; Xin Zhou ; ^{xinzhou@wipm.ac.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Non-small-cell lung cancer ; Magnetic resonance imaging ; Paclitaxel ; Carboplatin ; Liposome
• 刊名：Acta Biomaterialia
• 出版年：2016
• 出版时间：15 April 2016
• 年：2016
• 卷：35
• 期：Complete
• 页码：260-268
• 全文大小：3337 K

文摘

Liposomes are effective drug delivery systems that can be functionalized with imaging contrast agents, providing both diagnosis and monitoring of disease treatment. Here we describe the design of a theranostic liposomal drug delivery system whose biodistribution can be real time imaged by contrast enhanced MRI and can achieve tandem chemotherapy drug delivery. Because T₁ relaxation of MRI depends upon the chemical structure of contrast agent as well as its interaction with neighbor environment, we rationally designed a functional liposome for in vivo T₁ enhanced MRI. The liposome shows a 36-fold higher T₁ relaxation rate over the commercial MRI contrast agent Omniscan® and a long circulation time up to 300 min in vivo. Moreover, the multifunctional liposome carries both hydrophobic and hydrophilic chemotherapeutic drugs, can synergistically enhance therapeutic effects of multiple drugs and selectively deliver them to lung tumors, leading to lower doses, toxicity and sustained release. The nanoparticles, which exhibit favorable biodistributions to tumors, offer new possibilities for the simultaneous delivery of more than one drug and the evaluation of therapeutic response in vivo by T₁ enhanced MRI.

Statement of Significance

Cancer cells invoke different mechanisms to resist cancer therapies, particularly when delivering a single agent in a given therapy. The combination of two (or more) thermotherapy agents provides a promising way to circumvent such situations of drug resistance, due to a favorable synergistic effect that “tricks” the drug resistance mechanism.

However, challenges to the simultaneous delivery of two drugs prevail, especially with regards to the simultaneous delivery of hydrophobic and hydrophobic drugs. Furthermore, non-invasive in vivo imaging of drug distribution enables the real-time monitoring and prediction of therapeutic responses to treatment.

In this study, we rationally designed a theranostic liposomal drug delivery system whose biodistribution can be imaged via T₁-weighted MRI in real-time and can achieve tandem chemotherapy drug delivery. This original study will be of considerable use to the wider drug delivery community.