Tumor-Microenvironment-Responsive Biodegradable Nanoagents Based on Lanthanide Nucleotide Self-Assemblies toward...

Area of Science:

• Nanotechnology
• Materials Science
• Biomedical Engineering

Background:

• Stimuli-responsive nanoagents are crucial for precise cancer theranostics, balancing normal tissue clearance with tumor-specific treatment.
• Existing nanoagents face challenges in achieving efficient therapy while minimizing long-term toxicity.

Purpose of the Study:

• To develop a novel class of stimuli-responsive nanoagents for enhanced cancer theranostics.
• To synthesize and characterize self-assembled lanthanide nucleotide nanoparticles (LNNPs) with controlled properties.
• To evaluate the therapeutic potential and clearance mechanisms of LNNPs.

Main Methods:

• Template-induced self-assembly strategy for synthesizing LNNPs with tunable sizes (sub-5 nm to 105 nm).
• Low-temperature (10 K) and high-resolution spectroscopy to analyze the local site symmetry of lanthanide ions (Ln³⁺).
• In vitro assessment of doxorubicin loading, tumor-microenvironment-responsive release, biocompatibility, and renal clearance.

Main Results:

• Successfully synthesized amorphous LNNPs with controllable sizes via a template-induced self-assembly method.
• Elucidated the local site symmetry of Ln³⁺ within LNNPs using advanced spectroscopic techniques.
• Demonstrated efficient doxorubicin loading and responsive release triggered by the tumor microenvironment.
• Sub-5 nm LNNPs showed excellent biocompatibility, predominant renal clearance, and effective tumor retention.

Conclusions:

• LNNPs represent a promising new generation of therapeutic platforms for cancer theranostics.
• The developed LNNPs effectively address the critical challenge of balancing therapeutic efficacy with reduced long-term toxicity.
• These findings highlight the potential of LNNPs for future clinical applications in precision oncology.