Supramolecular Rotaxane-Based Multi-Modal Probes for Cancer Biomarker Imaging

被引：29

作者：

d'Orchymont, Faustine ^{[1
]}

Holland, Jason P. ^{[1
]}

机构：

[1] Univ Zurich, Dept Chem, Winterthurerstr 190, CH-8057 Zurich, Switzerland

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2022年 / 61卷 / 29期

基金：

瑞士国家科学基金会;

关键词：

Molecular Imaging; Molecularly Interlocked Molecules; Radiochemistry; Rotaxanes; Supramolecular Chemistry; CHEMISTRY; DELIVERY; CYCLODEXTRIN; ANTIBODIES; CATALYSIS;

D O I：

10.1002/anie.202204072

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Mechanically interlocked molecules present opportunities to construct therapeutic drugs and diagnostic imaging agents but harnessing supramolecular chemistry to make biologically active probes in water is a challenge. Here, we describe a rotaxane-based approach to synthesise radiolabelled proteins and peptides for molecular imaging of cancer biomarkers in vivo. Host-guest chemistry using beta-cyclodextrin- and cucurbit[6]uril-catalysed cooperative capture synthesis produced gallium-68 or zirconium-89 radiolabelled metallo[4]rotaxanes. Photochemical conjugation to trastuzumab led to a viable positron emission tomography (PET) radiotracer. The rotaxane architecture can be tuned to accommodate different radiometal ion complexes, other protein- or peptide-based drugs, and fluorophores for optical detection. This technology provides a platform to explore how mechanical bonding can improve drug delivery, enhance tumour specificity, control radiotracer pharmacokinetics, and reduce dosimetry.

引用

页数：11

共 56 条

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