Brush-like Polymer Prodrug with Aggregation-Induced Emission Features for Precise Intracellular Drug Tracking.

Area of Science:

• Polymer Chemistry
• Nanomedicine
• Bioconjugate Chemistry

Background:

• Developing advanced drug delivery systems is crucial for improving cancer therapy efficacy.
• Aggregation-induced emission (AIE) polymers offer unique optical properties for theranostics.
• Precise control over drug release and intracellular tracking remains a challenge in nanomedicine.

Purpose of the Study:

• To synthesize a brush-like polymer with AIE features for drug delivery and intracellular tracking.
• To create a prodrug by conjugating doxorubicin (DOX) to the AIE polymer.
• To evaluate the pH-sensitive drug release, cellular uptake, and anticancer efficacy of the developed prodrug.

Main Methods:

• Synthesis of a tetraphenylethene (TPE)- and oligo-poly(ethylene glycol) (PEG)-functionalized polymer via Cu(0)-mediated RDRP.
• Conjugation of doxorubicin (DOX) to the polymer through a pH-sensitive hydrazone linkage, forming TPE-PEGA-Hyd-DOX.
• In vitro evaluation of DOX release kinetics under different pH conditions and assessment of cellular uptake and cytotoxicity using confocal microscopy.

Main Results:

• The TPE-PEGA-Hyd-DOX prodrug demonstrated pH-sensitive release of DOX, with significantly higher release in acidic cancer cell environments compared to normal cell environments.
• Confocal microscopy revealed efficient cellular uptake of the prodrug and distinct AIE-based green fluorescence, alongside drug release indicated by red fluorescence in the cytoplasm.
• The prodrug exhibited low cytotoxicity in healthy cells while showing high performance in killing cancer cells.

Conclusions:

• The synthesized AIE-functionalized polymer prodrug (TPE-PEGA-Hyd-DOX) is a promising platform for targeted cancer therapy.
• The ratiometric fluorescence design enables precise intracellular drug tracking.
• The pH-sensitive hydrazone linkage ensures controlled drug release, enhancing therapeutic efficacy and minimizing off-target effects.