Supramolecular Chiral Binding Affinity-Achieved Efficient Synergistic Cancer Therapy

Area of Science:

• Biomaterials Science
• Supramolecular Chemistry
• Nanomedicine

Background:

• Supramolecular chirality is crucial for selective interactions in biological systems, impacting disease diagnosis and treatment.
• Understanding chiral binding affinity is key to optimizing therapeutic efficiency.

Purpose of the Study:

• To develop supramolecular chiral nanoparticles (WP5⊃D/L-Arg+DOX+ICG) for enhanced cancer therapy.
• To investigate the influence of chirality transfer from D/L-arginine to pillar[5]arene on nanoparticle binding and therapeutic outcomes.

Main Methods:

• Non-covalent assembly of water-soluble pillar[5]arene (WP5) with D/L-arginine (D/L-Arg) to create chiral nanoparticles.
• Loading of doxorubicin hydrochloride (DOX) as an anticancer drug and indocyanine green (ICG) as a photothermal agent.
• Evaluation of nanoparticle binding affinity to liposomes and in vitro/in vivo therapeutic efficacy.

Main Results:

• WP5⊃D-Arg nanoparticles exhibited 107-fold stronger binding to phospholipid liposomes than WP5⊃L-Arg nanoparticles.
• Enantioselective interactions led to targeted drug accumulation in cancer cells.
• WP5⊃D-Arg+DOX+ICG demonstrated significantly enhanced chemo-photothermal synergistic therapy with a 99.4% tumor inhibition rate, compared to 56.4% for WP5⊃L-Arg+DOX+ICG.

Conclusions:

• Supramolecular chirality plays a critical role in achieving highly selective interactions and superior therapeutic outcomes.
• The developed chiral nanoparticles offer a promising platform for advanced cancer treatment, highlighting the significance of supramolecular chirality in bio-applications.