Multi-Catcher Polymers Regulate the Nucleolin Cluster on the Cell Surface for Cancer Therapy

Area of Science:

• Biochemistry
• Nanotechnology
• Oncology

Background:

• Cell surface ligand-receptor interactions are vital for cellular behavior and apoptosis signaling.
• Targeting membrane receptor aggregation offers a promising avenue for cancer therapy, but stable models are challenging to create.

Purpose of the Study:

• To construct a stable nano-platform for regulating cell surface receptor aggregation.
• To develop a universal anti-tumor therapy model based on cytomembrane receptor clustering.

Main Methods:

• Designed a "multi-catcher" structure (GC-chol-apt-cDNA) integrating glycol chitosan (GC), cholesterol (chol), and oligonucleotide aptamer (apt).
• Utilized strong polyvalent binding and hydrophobic membrane anchoring for nucleolin cluster regulation on cell surfaces.
• Evaluated aptamer affinity, membrane anchoring stability, and anti-tumor efficacy in vitro and in vivo.

Main Results:

• The novel aptamer demonstrated nearly 100-fold higher affinity than monovalent aptamers.
• Achieved stable anchoring to the plasma membrane for up to 6 hours.
• Exhibited significant tumor inhibition by activating the endogenous mitochondrial apoptosis pathway via nucleolin clustering.

Conclusions:

• The developed multi-catcher nano-platform successfully regulates cytomembrane receptor clustering.
• This strategy combines spatial receptor regulation with intracellular apoptosis signaling for effective anti-tumor therapy.
• Represents a promising new approach for developing universal cancer treatments.