Departments of Radiology and Medical Physics , University of Wisconsin-Madison , Wisconsin 53705 , United States.
Interdisciplinary Innovation Institute of Medicine & Engineering, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Biological Science and Medical Engineering , Beihang University , Beijing 100191 , China.
J Am Chem Soc. 2018 Nov 7;140(44):14971-14979. doi: 10.1021/jacs.8b09374. Epub 2018 Oct 29.
The interaction between radionuclides and nanomaterials could generate Cerenkov radiation (CR) for CR-induced photodynamic therapy (PDT) without requirement of external light excitation. However, the relatively weak CR interaction leaves clinicians uncertain about the benefits of this new type of PDT. Therefore, a novel strategy to amplify the therapeutic effect of CR-induced PDT is imminently required to overcome the disadvantages of traditional nanoparticulate PDT such as tissue penetration limitation, external light dependence, and low tumor accumulation of photosensitizers. Herein, magnetic nanoparticles (MNPs) with Zr radiolabeling and porphyrin molecules (TCPP) surface modification (i.e., Zr-MNP/TCPP) were synthesized for CR-induced PDT with magnetic targeting tumor delivery. As a novel strategy to break the depth and light dependence of traditional PDT, these Zr-MNP/TCPP exhibited high tumor accumulation under the presence of an external magnetic field, contributing to excellent tumor photodynamic therapeutic effect together with fluorescence, Cerenkov luminescence (CL), and Cerenkov resonance energy transfer (CRET) multimodal imaging to monitor the therapeutic process. The present study provides a major step forward in photodynamic therapy by developing an advanced phototherapy tool of magnetism-enhanced CR-induced PDT for effective targeting and treatment of tumors.
放射性核素与纳米材料之间的相互作用可以产生切伦科夫辐射（CR），用于无需外部光激发的 CR 诱导光动力疗法（PDT）。然而，相对较弱的 CR 相互作用使得临床医生对这种新型 PDT 的益处不确定。因此，迫切需要一种新的策略来放大 CR 诱导 PDT 的治疗效果，以克服传统纳米颗粒 PDT 的缺点，如组织穿透限制、对外光的依赖性以及光敏剂在肿瘤中的低积累。在此，合成了带有 Zr 放射性标记和卟啉分子（TCPP）表面修饰的磁性纳米颗粒（MNPs）（即 Zr-MNP/TCPP），用于具有磁性靶向肿瘤递送的 CR 诱导 PDT。作为打破传统 PDT 的深度和光依赖性的一种新策略，这些 Zr-MNP/TCPP 在存在外部磁场的情况下表现出高肿瘤积累，有助于与荧光、切伦科夫发光（CL）和切伦科夫共振能量转移（CRET）多模态成像一起实现出色的肿瘤光动力治疗效果，以监测治疗过程。本研究通过开发一种先进的磁增强 CR 诱导 PDT 光疗工具，为有效靶向和治疗肿瘤提供了重要的一步。
