Small Molecular Prodrug Amphiphile Self-Assembled AIE Dots for Cancer Theranostics.

Xiuli Xu,Ping Gong,Defang Ouyang,Yingxia Bao,Xingxing Fan,Lintao Cai,Jiaming Yang,Xing Yang,Sanpeng Li,Yuan Luo

doi:10.3389/fbioe.2020.00903

Abstract

A simple and facile one-step method was developed to construct a small molecular prodrug amphiphile self-assembled organic dots CPPG with aggregation-induced emission (AIE) characteristics. Diphenylalanine peptide (FF), which is the essential moiety of the self-assembling peptide-drug conjugate and as its core recognition motifs for molecular self-assembly. In addition, the D-glucose transported protein (GLUT), which is one of the important nutrient transporters and is overexpressed in cancer cells. The conjugation of glycosyl further endues the nanoparticle with good biocompatibility and tumor-targeting ability. Taking advantages of both the cancer cell-targeting capability of small molecular prodrug amphiphile CPPG and the AIE aggregates with strong emission, the prepared CPPG AIE dots can target cancer cells specifically and inhibit the proliferation of cancer cells with good biocompatibility and photostability. Based on the general approach, types of universal organic fluorescent nanoprobes could be facilely constructed for imaging applications and biological therapeutics, which possess the properties of specific recognition and high brightness.

Highlights

Fluorescence imaging is a low-cost and highly sensitive method for the diagnosis of early tumors, visualization of tumor margins, and evaluation of treatment effects (Ozawa et al, 2013; Weissleder and Nahrendorf, 2015; Antaris et al, 2016)
With the CPPG aggregation-induced emission (AIE) dots in hand, we first investigated the spectral characteristics, all the test samples are from 4 mg/mL CPPG AIE dots, the UV/Vis absorption spectrum of CPPG AIE dots dispersion displayed typical signals of TTF at ∼480 nm and the peak of CPPG at ∼370 nm (Figure 1A and Supplementary Figure S12), as for the fluorescence emission spectra, CPPG AIE dots show a emission peak at ∼650 nm (Figure 1B), which further confirmed the successfully synthesized of CPPG AIE dots
Dynamic light scattering (DLS) analysis revealed that the average diameter of CPPG AIE dots was ∼57 nm (Figure 1C), the uniform spherical morphology was confirmed by transmission electron microscopy (TEM) analysis (Figure 1D)

Summary

Introduction

Fluorescence imaging is a low-cost and highly sensitive method for the diagnosis of early tumors, visualization of tumor margins, and evaluation of treatment effects (Ozawa et al, 2013; Weissleder and Nahrendorf, 2015; Antaris et al, 2016). Compared with the traditional organic molecules, nanoparticles usually possess better photostability, higher brightness, and larger absorption coefficients, which make them able to enhance the versatility and sensitivity of fluorescence-based imaging and diagnosis. To develop organic dye nanoparticles with significantly enhanced biocompatibility and photostability have taken great efforts (Wang et al, 2013). The brightness of the organic nanoparticles, gradually decrease along with the increase of dye concentration. The strong emissions of the solidstate AIEgens offer a great opportunity for developing highly bright organic nanoparticles, known as AIE dots, without blemishing their emissions (Zhang X. et al, 2015; Xu et al, 2016; Yan et al, 2016; Li H. et al, 2017; Niu et al, 2019)

Methods

Results

Conclusion