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Updated: Jul 19, 2026
Synthesis, Cellular Delivery and In vivo Application of Dendrimer-based pH Sensors
Published on: September 10, 2013
"Off-on-off"-based metal-organic framework fluorescent sensor for adenosine triphosphate detection and tumor
Tianqian Jia1, Ke Wang1, Xiaojuan Li1
1School of Medical Engineering, Haojing College of Shaanxi University of Science & Technology, Xianyang, 712046, Shaanxi, PR China.
Abstract:
Extracellular adenosine triphosphate (ATP) and low extracellular pH are emerging targets for cancer treatment because they are crucial messengers shaping the tumor microenvironment (TME) and regulating tumor progression. Doxorubicin (Dox) is a common chemotherapeutic agent used against numerous solid tumors; however, its use is limited by its adverse effects, such as cardiotoxicity in healthy cells/tissues and multidrug resistance. Thus, using targeted nanocarriers can reduce the side effects of Dox. Herein, we report the construction of an ATP-responsive high fluorescent nanocomposite (ANZIF) that uses gold nanocluster self-assembly embedded in a zeolitic imidazolate framework-8. Based on "off-on-off" fluorescence changes, the ANZIF can be used for sensitive and selective ATP detection, with a detection limit of 4.3 μM. The ANZIF nanoplatform was fabricated using a self-assembly strategy for Dox loading (Dox-ANZIF). This unique nanoplatform exhibited ATP- and low-pH dual-triggered Dox release. In a cytotoxicity study, Dox-ANZIF, triggered by intracellular ATP and low pH, exhibited a selective release of Dox and showed a strong role in cancer cells. Compared with pure Dox, in vivo anticancer efficacy in tumor-bearing mice indicated that Dox-ANZIF significantly improved the antitumor effect and biological safety. This study provides a strategy for constructing a TME-triggered chemotherapy delivery system.
Insights
This study introduces a novel ATP-responsive nanocomposite for targeted chemotherapy. The system selectively releases Doxorubicin (Dox) in the tumor microenvironment (TME), enhancing anticancer efficacy and improving safety.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapeutics
Background:
- Extracellular adenosine triphosphate (ATP) and low pH are key regulators of the tumor microenvironment (TME).
- Doxorubicin (Dox) is effective but limited by cardiotoxicity and multidrug resistance.
- Targeted nanocarriers can mitigate Dox side effects and improve delivery.
Purpose of the Study:
- To develop an ATP-responsive fluorescent nanocomposite for targeted Doxorubicin (Dox) delivery.
- To create a system for sensitive ATP detection within the tumor microenvironment (TME).
- To evaluate the dual-triggered release and in vivo anticancer efficacy of the Dox-loaded nanoplatform.
Main Methods:
- Fabrication of an ATP-responsive gold nanocluster/zeolitic imidazolate framework-8 nanocomposite (ANZIF).
- Loading Doxorubicin (Dox) into the ANZIF via self-assembly to create Dox-ANZIF.
- Assessment of fluorescence-based ATP detection and dual-triggered Dox release (ATP and low pH).
- In vitro cytotoxicity assays and in vivo anticancer efficacy studies in tumor-bearing mice.
Main Results:
- The developed nanocomposite (ANZIF) demonstrated sensitive and selective ATP detection (limit of 4.3 μM) with "off-on-off" fluorescence.
- Dox-ANZIF exhibited dual-triggered release of Dox in response to intracellular ATP and low pH.
- Dox-ANZIF showed enhanced selective cytotoxicity against cancer cells compared to free Dox.
- In vivo studies revealed significantly improved antitumor effects and biological safety for Dox-ANZIF over pure Dox.
Conclusions:
- A novel ATP-responsive, high-fluorescent nanocomposite (ANZIF) was successfully constructed.
- The Dox-ANZIF nanoplatform enables targeted chemotherapy by leveraging tumor microenvironment (TME) triggers (ATP and low pH).
- This TME-triggered drug delivery system offers improved anticancer efficacy and safety, presenting a promising strategy for cancer treatment.
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