Fabrication and Properties of pH-Sensitive Graphene Quantum Dot Multi-Level Assemblies for Tumor Microenvironment-Responsive Imaging

ZHANG Bin; GU Yinger; ZHANG Lingjie; LI Fangcai; WANG Zhiwei; ZHU Chengyue; CHU Liangyong; BAO Ningzhong

doi:10.11949/0438-1157.20260712

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Fabrication and Properties of pH-Sensitive Graphene Quantum Dot Multi-Level Assemblies for Tumor Microenvironment-Responsive Imaging

更新时间：2026-06-15

- Fabrication and Properties of pH-Sensitive Graphene Quantum Dot Multi-Level Assemblies for Tumor Microenvironment-Responsive Imaging
- CIESC Journal (2026)
- 作者机构：
  
  1.浙江大学材料科学与工程学院，浙江杭州 310058
  2.南京工业大学材料化学工程全国重点实验室，江苏南京 211816
  3.浙大城市学院工程学院，浙江杭州 310015
  4.浙江大学台州研究院，浙江台州 318012
  5.浙江省土产畜产进出口集团有限公司，浙江杭州 310005
  6.浙江大学医学院附属妇产科医院，浙江杭州 310006
  7.浙江大学医学院附属第二医院，浙江杭州 310009
- 作者简介：
- 基金信息：
- DOI：10.11949/0438-1157.20260712
  CLC：
- Received：25 May 2026，
  
  Revised：2026-06-12，
  
  Accepted：15 June 2026，
- 稿件说明：
移动端阅览
ZHANG Bin, GU Yinger, ZHANG Lingjie, et al. Fabrication and Properties of pH-Sensitive Graphene Quantum Dot Multi-Level Assemblies for Tumor Microenvironment-Responsive Imaging[J/OL]. CIESC Journal, 2026.
DOI：

ZHANG Bin, GU Yinger, ZHANG Lingjie, et al. Fabrication and Properties of pH-Sensitive Graphene Quantum Dot Multi-Level Assemblies for Tumor Microenvironment-Responsive Imaging[J/OL]. CIESC Journal, 2026. DOI： 10.11949/0438-1157.20260712.

摘要

石墨烯量子点（GQDs）因优异的光学特性在生物成像领域备受关注。针对传统GQDs制备尺寸不均、荧光波长较短及细胞穿透性不足的难题，本文提出基于表面化学调控与pH响应组装的设计策略，以氧化石墨烯（GO）为前驱体，通过过氧化氢（H₂O₂）选择性刻蚀与铂催化除杂，制备了高羧基含量（49.54%）的GQDs；之后通过酰胺键接枝聚乙烯亚胺（PEI）构建氨基化组装体（PGs），并利用席夫碱反应引入双醛聚乙二醇（DA-PEG），获得兼具肿瘤微环境响应特性的多级组装体（PPGs）。通过TEM、XPS、FT-IR等方法对材料的结构与形貌进行了表征，研究了反应时间、物料配比等工艺参数对GQDs光学性能及生物相容性的影响。研究表明，当水热反应时间为100 min、PEI:GQDs质量比为10:1、PGs:DA-PEG质量比为10:1时，制得的PPGs粒径约90 nm，荧光发射波长红移至580 nm（橙黄光），在pH=6.8的肿瘤微环境中苯甲酰亚胺键断键率达38.57%，实现可控解组装；与文献报道的单纯PEI修饰GQDs相比，相同浓度下的细胞毒性降低60%，细胞摄取效率提升3倍以上，且具备双发射荧光（440 nm/600 nm）特性。本文报道的多级组装设计，为开发高生物安全性、高特异性的肿瘤荧光探针提供了创新思路，为体外肿瘤细胞水平的可视化检测提供了一种潜在的探针设计策略。

Abstract

Graphene quantum dots (GQDs) have garnered significant attention in the field of bioimaging due to their exceptional optical properties. To address the challenges of traditional GQDs

including non-uniform size distribution

short fluorescence emission wavelengths

and insufficient cell penetration

this study proposes a design strategy based on surface chemistry modulation and pH-responsive assembly. Using graphene oxide (GO) as a precursor

highly carboxylated GQDs (carboxyl content: 49.54%) were fabricated via selective etching with hydrogen peroxide (H₂O₂) coupled with platinum-catalyzed impurity removal. Subsequently

amino-functionalized assemblies (PGs) were constructed by grafting polyethyleneimine (PEI) onto the GQDs via amide bonds. Finally

multi-level assemblies (PPGs) featuring tumor microenvironment responsiveness were obtained by introducing dialdehyde-terminated poly(ethylene glycol) (DA-PEG) through Schiff base reactions. The structure and morphology of the materials were characterized using transmission electron microscopy (TEM)

X-ray photoelectron spectroscopy (XPS)

and Fourier-transform infrared spectroscopy (FT-IR). The effects of process parameters

such as reaction time and material ratios

on the optical performance and biocompatibility of the GQDs were systematically investigated. The results indicate that under optimal conditions—hydrothermal reaction time of 100 min

PEI:GQDs mass ratio of 10:1

and PGs:DA-PEG mass ratio of 10:1—the resulting PPGs exhibited an average particle size of approximately 90 nm and a red-shifted fluorescence emission peak at 580 nm (orange-yellow light). In a simulated tumor microenvironment (pH = 6.8)

the benzoimide bonds achieved a cleavage rate of 38.57%

enabling controlled disassembly. Compared to previously reported GQDs modified solely with PEI

the optimized PPGs demonstrated a 60% reduction in cytotoxicity and a more than threefold increase in cellular uptake efficiency at equivalent concentrations

while exhibiting dual-emission fluorescence characteristics (440 nm/600 nm). This work presents a "rigid-flexible coupled" multi-level assembly design

offering innovative insights for developing tumor-targeted fluorescent probes with high biosafety and specificity

thereby providing a potential probe design strategy for the visualization detection of tumor cells at the in vitro cellular level.

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references

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