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Displaying In Vivo "Assembly-Disassembly" Cascade with "Off-On-Off" Magnetic Resonance Imaging Signals in Tumor

Hai-Dong Xu1, Xianbao Sun1, Zheng Huang2

  • 1State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 211189, China.

Journal of the American Chemical Society
|June 24, 2025
PubMed

Insights

Researchers developed a novel gadolinium probe for real-time in vivo monitoring of tumor theranostics. This probe visualizes the "Assembly-Disassembly" cascade using magnetic resonance imaging (MRI), overcoming previous limitations in dynamic monitoring.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Medical Imaging

Background:

  • The "Assembly-Disassembly" cascade is crucial for tumor theranostics but lacks real-time in vivo monitoring capabilities.
  • Existing methods struggle to balance penetration depth and real-time tracking of dynamic processes.
  • Integrating both features for in vivo cascade visualization remains an unmet challenge.

Purpose of the Study:

  • To develop a novel gadolinium (Gd) probe for real-time in vivo monitoring of the "Assembly-Disassembly" cascade in tumor theranostics.
  • To achieve integrated real-time display of dynamic cascade processes in a living organism using MRI.
  • To overcome the limitations of current theranostic monitoring strategies.

Main Methods:

  • Development of a Gd probe, Cys(StBu)-Asp-Asp-Asp-Asp-Lys-Lys(DOTA(Gd))-CBT (Gd-AD), for T1-weighted 1H magnetic resonance imaging (MRI).
  • Utilizing a CBT-Cys click reaction for nanoparticle assembly under reduction conditions.
  • Employing enterokinase (ENTK) cleavage for nanoparticle disassembly.
  • Comparative study with a scrambled control probe (Gd-A) for validation.

Main Results:

  • Gd-AD demonstrated an "Off-On-Off" T1-weighted 1H MRI signal change reflecting the "Assembly-Disassembly" cascade in vitro and in vivo.
  • Assembly led to enhanced MRI signals (59.3% in cells, 25.4% in tumors); disassembly decreased signals (23.4% in cells, 15.2% in tumors).
  • Gd-AD clearly showed "Off-On-Off" signals during 1-hour tumor imaging, unlike the control Gd-A's "Off-On" signals.

Conclusions:

  • The developed Gd-AD probe enables real-time in vivo visualization of the "Assembly-Disassembly" cascade in tumor theranostics.
  • This strategy integrates penetration depth and real-time monitoring, addressing a critical gap in current theranostic approaches.
  • The findings offer a promising platform for optimizing nanodrug-based tumor theranostics through dynamic cascade monitoring.

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