Abstract

Optical imaging probes have played a major role in detecting and monitoring a variety of diseases. In particular, nonlinear optical imaging probes, such as second harmonic generating (SHG) nanoprobes, hold great promise as clinical contrast agents, as they can be imaged with little background signal and unmatched long-term photostability. As their chemical composition often includes transition metals, the use of inorganic SHG nanoprobes can raise long-term health concerns. Ideally, contrast agents for biomedical applications should be degraded in vivo without any long-term toxicological consequences to the organism. Here, we developed biodegradable harmonophores (bioharmonophores) that consist of polymer-encapsulated, self-assembling peptides that generate a strong SHG signal. When functionalized with tumor cell surface markers, these reporters can target single cancer cells with high detection sensitivity in zebrafish embryos in vivo. Thus, bioharmonophores will enable an innovative approach to cancer treatment using targeted high-resolution optical imaging for diagnostics and therapy.

Highlights

  • Optical imaging probes have played a major role in detecting and monitoring a variety of diseases

  • To render these nanostructures suitable for biological applications, we evaluated methods for the encapsulation of self-assembling peptides in order (i) to hinder their macroscopic aggregation by confining their self-assembly in nanodroplets without affecting their ability to generate a strong second harmonic generating (SHG) signal and (ii) to generate a nanoparticle that can be further functionalized without influencing the peptide assembly

  • We introduced bioharmonophores as a class of imaging probes that retain all the photophysical advantages of previously introduced inorganic SHG nanoprobes

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Summary

Introduction

Optical imaging probes have played a major role in detecting and monitoring a variety of diseases. We introduced inorganic second harmonic generating (SHG) nanocrystals, SHG nanoprobes,[6] as a class of imaging probes that can be used for in vivo imaging.[7] Given that SHG imaging employs near-infrared (NIR) incident light for contrast generation, SHG nanoprobes can be utilized for deep tissue imaging.[8,9] Unlike commonly used fluorescent probes, SHG nanoprobes neither bleach nor blink, and their signal does not saturate with increasing illumination intensity, ensuring high probe sensitivity.[10] Since their signal profile is very narrow, they can be imaged with high SNR by excluding the broad emission of typical autofluorescence background.[6,11] Robust functionalization allows targeting to a wide variety of cells and proteins of interest,[12] allowing these imaging probes to be promising tools for both clinical and preclinical imaging applications.[13] Despite these advantages, the chemical structure of inorganic SHG nanoprobes makes them stable in the body, which may cause concerns for the long-term health of an organism that has been imaged with these reporters.[14]. Miniaturized peptide assemblies should not lose their crystalline structure and SHG signal, generating imaging agents that can be degraded over time without harming the body

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