Split and Use: Structural Isomers for Diagnosis and Therapy

Diagnostics
and therapeutics are generally separate entities in
medicine. Theranostics, agents that provide for both modalities, are
being developed. However, they often require complex syntheses so
as to incorporate within one molecular structure both diagnostic and
therapeutic elements. Moreover, their use is often complicated by
the disparate dosage requirements for diagnosis and therapy. Herein,
we report that closely related porphyrinoid regioisomers produced
from the same 1,3-dipolar cycloaddition reaction give rise to products
that as their corresponding ytterbium­(III) complexes may be split
and used for the separate biological functions that are required for
theranostics. Specifically, the cis isomer is luminescent
and suitable for NIR imaging, while the trans isomer
produces singlet oxygen with a good quantum yield and is thus attractive
for use in photodynamic therapy (PDT). Both in vitro and in vivo experiments
provide support for the complementary biological functions of the
two regioisomers. The present study reveals how ostensibly related
regioisomers may be used to switch between diagnosis and therapy.
More broadly, it serves to highlight a new approach to creating paired
sets of molecules that may be used in combination as effective theranostics.

在医学领域，诊断与治疗通常是相互独立的分支。兼具诊断与治疗双重功能的诊疗一体化制剂（Theranostics）正处于研发阶段。然而，这类制剂往往需要复杂的合成工艺，才能将诊断与治疗元件整合至同一分子结构中。此外，其临床应用常因诊断与治疗所需剂量差异显著而面临诸多挑战。本文报道，由同一1,3-偶极环加成（1,3-dipolar cycloaddition）反应制得的结构密切相关的卟啉类区域异构体（porphyrinoid regioisomers），其对应的镱(III)配合物可被拆分并分别用于诊疗一体化所需的不同生物学功能。具体而言，顺式异构体具有发光特性，适用于近红外（NIR）成像；反式异构体可产生单线态氧，且量子产率优异，因此在光动力疗法（PDT）中具备良好应用价值。体外（in vitro）与体内（in vivo）实验均证实了这两种区域异构体的生物学功能具有互补性。本研究揭示了结构看似相近的区域异构体如何实现诊断与治疗功能的切换。更广泛而言，本研究为构建可组合使用的成对分子体系以开发高效诊疗一体化制剂提供了全新思路。