Current trends and key considerations in the clinical translation of targeted fluorescent probes for intraoperative navigation

Abstract

The rapid development of fluorescence imaging for intraoperative navigation has spurred further development of targeted fluorescent probes in the past decade. Only a few nontargeted dyes, including indocyanine green and methylene blue, are currently applied for fluorescence guided surgery in the clinic. While no targeted fluorescent probes have been approved for the clinic, a number of them have entered clinical trials. These probes have emission wavelengths in the visible and near infrared (NIR)‐I (700‐900 nm) range. Among them, activatable probes and nanoprobes have generated special interest. Compared with NIR‐I fluorescent probes, NIR‐II (1000‐1700 nm) fluorescent probes exhibit better intravital performance in terms of increased penetration depths, reduced tissue autofluorescence, and higher signal‐to‐background ratios. However, more challenges are expected before the successful translation of NIR‐II probes from bench to bedside. This review provides a brief overview of targeted fluorescent probes under clinical evaluation and recent achievements in the field of NIR‐II fluorescence imaging. In addition, we outline key considerations concerning the design of fluorescent probes for clinical translation.

A first-in-human study of BLZ-100 (tozuleristide) demonstrates tolerability and safety in skin cancer patients

“…Strategies include targeting with antibodies to known tumor antigens such as EGFR or CEA, targeting with peptides such as cRGD or small molecules such as folate that interact with tumor antigens or tumor vasculature, creating cleavable constructs that are activated by proteases within the tumor milieu, creating pH-sensitive constructs that are activated in the low pH environment of the tumor, metabolic labeling with 5-ALA, as well as continued study of non-targeted agents that accumulate in tumor tissue due to the enhanced permeability and retention (EPR) effect (reviewed in Refs. [ [12] , [13] , [14] ]). Indications with high unmet need, such as head and neck cancer and brain tumors, have received particularly intense attention (reviewed in Refs.…”

High‐performance nano‐splitters containing aggregation‐induced emission luminogens for stereoselective crystallization obtained via polymerization‐induced self‐assembly

“…[ 49–51 ] Besides, AIEgens are advantageous for wash‐free imaging that the discrete luminogens in solution make almost no contribution to the total emission in comparison to the encapsulated luminogens in the assemblies. [ 52–55 ]…”

“…[49][50][51] Besides, AIEgens are advantageous for wash-free imaging that the discrete luminogens in solution make almost no contribution to the total emission in comparison to the encapsulated luminogens in the assemblies. [52][53][54][55] Herein, we described a strategy for the efficient production of "nano-splitters" with AIE fluorescence probes entrapped into the hydrophobic zones through PISA process in one pot (Figure 1A). The solid content was significantly raised (14%∼22%, Figure 1B) with a good dispersibility.…”

Endowing AIE with Extraordinary Potential: A New Au(I)‐Containing AIEgen for Bimodal Bioimaging‐Guided Multimodal Synergistic Cancer Therapy

“…They not only enable the direct visualization of various biologically relevant species and activities, but also provide powerful therapeutic functions to be one of the best theranostic platforms. [ 1–6 ] On the other hand, aggregation‐induce emission luminogens (AIEgens) are a distinctive type of promising luminescent materials and exhibit unparalleled superior in biomedical applications due to their stronger luminescence and photoactivity than traditional luminescent fluorophores with aggregation‐caused quenching effect. [ 7–10 ] In the past few years, a myriad of AIEgens have been developed and have attracted burgeoning attentions in both bioimaging and image‐guided therapy, specifically including various cancer cell imaging, tumor imaging, microbial detection, long‐term cell tracing, super‐resolution imaging, disease surveillance, drug delivery tracking, image‐guided chemotherapy, photodynamic therapy, photothermal therapy, immunotherapy, etc.…”