Abstract

An ideal cancer diagnostic probe should possess precise tumor-targeted accumulation with negligible sojourn in normal tissues. Herein, tumor cell-derived carbon nanodots (C-CNDU87 and C-CNDHepG2) about 3~7 nm were prepared by a solvothermal method with stable fluorescence and negligible cytotoxicity. More interestingly, due to the differences in gene expression of cancers, C-CND structurally mimicked the corresponding precursors during carbonization in which carbon nanodots were functionalized with α-amino and carboxyl groups with different densities on their edges. With inherent homology and homing effect, C-CND were highly enriched in precursor tumor tissues. Mechanistic studies showed that under the mediation of the original configuration of α-amino and carboxyl groups, C-CND specifically bound to the large neutral amino acid transporter 1 (LAT1, overexpressed in cancer cells), achieving specific tumor fluorescence imaging. This work provided a new vision about tumor cell architecture-mimicked carbon nanodots for tumor-targeted fluorescence imaging.

Highlights

  • Mechanisms of Tumor Cell-DerivedCarbon nanodots (CND) have shown great potential in cancer diagnosis and treatment based on readily available materials, facile synthesis techniques, highly tunable fluorescence properties, and natural biocompatibility [1,2]

  • It is believed that when confronted with cancer, Cell-DerivedCarbon nanodots (CND) prepared by tumor cells, where the composition of surface functional groups and carbon nanodot skeleton are regulated by precursor genes, might exhibit more specific and desirable tumor-targeted capacity than those prepared by the artificial mass ratio regulation of exogenous raw materials

  • The molecular structure and chemical component contents of C-CND were evaluated by X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared (FT-IR) spectroscopy and 13 C and 1 H nuclear magnetic resonance (NMR) spectrum

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Summary

Introduction

Carbon nanodots (CND) have shown great potential in cancer diagnosis and treatment based on readily available materials, facile synthesis techniques, highly tunable fluorescence properties, and natural biocompatibility [1,2]. Compared with the synthesis of carbon nanodots using non-renewables, the bio-based raw materials regarded as precursors are possibly more popular and sustainable Both plantand animal-based carbon sources have been widely explored for CND preparation [15,16,17], and cells, the basic structural and functional unit of organism, are adept at carrying out defined functions within complex environment. It is believed that when confronted with cancer, CND prepared by tumor cells, where the composition of surface functional groups and carbon nanodot skeleton are regulated by precursor genes, might exhibit more specific and desirable tumor-targeted capacity than those prepared by the artificial mass ratio regulation of exogenous raw materials. Under the mediation of α-amino and carboxyl groups, C-CND bound to LAT1, quickly and preferentially entered their precursor cells, achieving the tumor-targeted accumulation and promising fluorescence imaging

Schematic diagram of in vivo imaging
Cell lines and Animals
Preparation
Characterizations
Fluorescence Stability
BCA Test
SDS-PAGE Analysis
Cellular Uptake
Subcellular Localization of C-CND
Sample Preparation
2.10. Construction of Tumor-Bearing Mice Models
2.11. In Vivo Tissue Distribution
2.12. Study on the Relationship between C-CND and Tumor Proliferation
2.13. Tumorigenicity Study
Results and Discussion
H2 H3 H4 H5 H6 U1 U2 U3 U4 U5 U6
Conclusions
Full Text
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