Neurotoxin-Derived Optical Probes for Biological and Medical Imaging

Abstract

The superb specificity and potency of biological toxins targeting various ion channels and receptors are of major interest for the delivery of therapeutics to distinct cell types and subcellular compartments. Fused with reporter proteins or labelled with fluorophores and nanocomposites, animal toxins and their detoxified variants also offer expanding opportunities for visualisation of a range of molecular processes and functions in preclinical models, as well as clinical studies. This article presents state-of-the-art optical probes derived from neurotoxins targeting ion channels, with discussions of their applications in basic and translational biomedical research. It describes the design and production of probes and reviews their applications with advantages and limitations, with prospects for future improvements. Given the advances in imaging tools and expanding research areas benefiting from the use of optical probes, described here resources should assist the discovery process and facilitate high-precision interrogation and therapeutic interventions.

Keywords: Advanced biomaterials; Animal toxins; Fluorescent probes; ICG; Ion channels; Optical imaging; Visualisation.

Fig. 1

An overview of animal toxins targeting ion channels used for biomedical imaging. A Representation of major neurotoxins with target ion channels utilised for optical imaging in basic and translational studies. B Illustration of general strategy and approaches used for targeting neurotoxin-derived optical probes to ion channels with a representative in vitro (CHO cells expressing K_V2.1 and K_V2.2 labelled with GxTx labelled with Alexa594) and in vivo (mice grafted with SKOV3 tumours labelled with SOR-C27-Cy5.5) data. Images are reproduced with permission, with detailed explanations provided in respective parts of the review

Fig. 2

Animal toxin-derived optical probes targeting ion channels for biomedical research and clinical application. List of ion channel targets (left column) of animal toxins (middle column) used for research tagged with fluorophores, reporter proteins and nanomaterials (right column). Fluorophores and reporter proteins are aligned against the visible spectrum bar (top) to illustrate their peak absorbance. Fluorescence labels and reporters used for targeted toxins with a wide absorbance range or with a peak absorbance outside of the visible spectrum are listed on the left and right margins of the right column, respectively. QD, quantum dots; NG, nanogold; PBD, polymer-blend dots; DOX, doxorubicin; DIR, dye R; cFND, fluorescent nanodiamonds with carboxyl; ICG, indocyanine green; IRD800CW, infrared dye 800CW

Fig. 3

Representation of basic and translational research areas of the use of animal toxin-derived optical probes targeting ion channels. List of ion channels (left column) targeted by labelled animal toxins (middle column) utilised for various research and translational applications (red circle). The details of the applications of each optical probe are described in corresponding sections of the review