Visualizing Photodynamic Therapy in Transgenic Zebrafish Using Organic Nanoparticles with Aggregation-Induced Emission

Purnima Naresh Manghnani,Wenbo Wu,Cathleen Teh,Shidang Xu,Bin Liu,Fang Hu

doi:10.1007/s40820-018-0214-4

Abstract

Photodynamic therapy (PDT) employs accumulation of photosensitizers (PSs) in malignant tumor tissue followed by the light-induced generation of cytotoxic reactive oxygen species to kill the tumor cells. The success of PDT depends on optimal PS dosage that is matched with the ideal power of light. This in turn depends on PS accumulation in target tissue and light administration time and period. As theranostic nanomedicine is driven by multifunctional therapeutics that aim to achieve targeted tissue delivery and image-guided therapy, fluorescent PS nanoparticle (NP) accumulation in target tissues can be ascertained through fluorescence imaging to optimize the light dose and administration parameters. In this regard, zebrafish larvae provide a unique transparent in vivo platform to monitor fluorescent PS bio-distribution and their therapeutic efficiency. Using fluorescent PS NPs with unique aggregation-induced emission characteristics, we demonstrate for the first time the real-time visualization of polymeric NP accumulation in tumor tissue and, more importantly, the best time to conduct PDT using transgenic zebrafish larvae with inducible liver hyperplasia as an example.

Highlights

Photodynamic therapy (PDT) is a noninvasive triggered therapeutic modality, which involves the use of photosensitizer (PS) molecules capable of generating reactive oxygen species (ROS) upon light excitation for treatment of malignant and non-malignant tumors
Using fluorescent PS NPs with unique aggregation-induced emission characteristics, we demonstrate for the first time the real-time visualization of polymeric NP accumulation in tumor tissue and, more importantly, the best time to conduct PDT using transgenic zebrafish larvae with inducible liver hyperplasia as an example
Since the electron donor and acceptor groups of the PS molecule are linked by a single bond, when a polar solvent like water is introduced into the solvent, such molecules can undergo fast intramolecular electron transfer, which is accompanied by intramolecular donor–acceptor twisting around the single bond

Summary

Introduction

Photodynamic therapy (PDT) is a noninvasive triggered therapeutic modality, which involves the use of photosensitizer (PS) molecules capable of generating reactive oxygen species (ROS) upon light excitation for treatment of malignant and non-malignant tumors. Using fluorescent PS NPs with unique aggregation-induced emission characteristics, we demonstrate for the first time the real-time visualization of polymeric NP accumulation in tumor tissue and, more importantly, the best time to conduct PDT using transgenic zebrafish larvae with inducible liver hyperplasia as an example. A combination of therapeutic and imaging modalities for PDT enables real-time tracking, cancer characterization, targeted delivery, triggered drug release and pharmacokinetic profiling.

Results

Conclusion