Robust Red Organic Nanoparticles for In Vivo Fluorescence Imaging of Cancer Cell Progression in Xenografted Zebrafish

Abstract

Bright and red-emissive organic nanoparticles (NPs) are demonstrated as promising for in vivo fluorescence imaging. However, most red organic dyes show greatly weakened or quenched emission in the aggregated state. In this work, a robust red fluorophore (t-BPITBT-TPE) with strong aggregatestate photoluminescence and good biocompatibility is presented. The NPs comprised of t-BPITBT-TPE aggregates encapsulated within 1,2-distearoyl-snglycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol) (DSPE-mPEG) micelles exhibit a photoluminescence peak at 660 nm with a high fluorescence quantum yield of 32% in aqueous media. The NPs can be facilely charged by using the same polymeric matrix with different terminal groups, e.g., methoxy (DSPE-mPEG), amine (DSPE-PEG-NH 2 ), or carboxymethyl (DSPE-PEG-COOH) groups. The biocompatibility, toxicity, circulation, and biodistribution of the NPs are assessed using the zebrafish model through whole embryo soaking and intravenous delivery. Furthermore, HeLa and MCF-7 cells tagged with t-BPITBT-TPE in DSPE-PEG-NH 2 -TAT polymer NPs are xenografted into zebrafish larvae to successfully track the cancer cell proliferation and metastasis, demonstrating that these new NPs are efficient cancer cell trackers. In addition, the NPs also show good in vivo imaging ability toward 4T1 tumors in xenografted BALB/c mice.

Intrinsically Fluorescent, Stealth Polypyrazoline Nanoparticles with Large Stokes Shift for In Vivo Imaging

“…Recently, zebrafish embryos have been successfully used to establish patient derived tumor xenografts and accurately predict the response to chemotherapy . For these reasons, the zebrafish model has also emerged as an attractive alternative to rodents for the investigation of drug delivery systems with regard to targeting efficiency and clearance . The extra‐uterine development of the small transparent embryos and larvae allows in particular real‐time imaging at highest resolution, which is unmatched by other vertebrate models like mouse or rat.…”

“…[36] For these reasons, the zebrafish model has also emerged as an attractive alternative to rodents for the investigation of drug delivery systems with regard to targeting efficiency and clearance. [37][38][39] The extra-uterine development of the small transparent embryos and larvae allows in particular real-time imaging at highest resolution, which is unmatched by other vertebrate models like mouse or rat. Zebrafish embryos are thus ideal first-line models to assess the toxicity and the distribution of nanoparticles.…”

Organic Mitoprobes based on Fluorogens with Aggregation‐Induced Emission

“…As the emission color of AIEgens can be fine-tuned with a wide range from blue to the second near-infrared window, [39,57,58] so far, AIE mitoprobes with different emission colors have been developed. Among them, TPE, [37] salicylaldehyde azine (SAA) are typical AIEgens with greenish blue and green emission colors, respectively.…”

Semiconducting polymer dots as near‐infrared fluorescent probes for bioimaging and sensing

“…[1] Nowadays, these techniques have been playing a crucial role in clinical research and diagnosis of diseases. [1] Nowadays, these techniques have been playing a crucial role in clinical research and diagnosis of diseases.…”

“…Biomedical imaging techniques open a new gate for scientists to explore subcellular structures of living organisms and to unveil the mechanisms of biological activities related to diseases. [1] Nowadays, these techniques have been playing a crucial role in clinical research and diagnosis of diseases. The use of medical imaging ranges from the detection of early stage diseases and the evaluation of results of medical treatment to the follow up the progression of diseases.…”