Supramolecular polymeric chemotherapy based on cucurbit[7]uril-PEG copolymer

Area of Science:

• Supramolecular Chemistry
• Polymer Science
• Nanomedicine
• Cancer Therapy

Background:

• Supramolecular polymers offer unique drug delivery platforms.
• Cucurbit[7]uril (CB[7]) is a macrocycle capable of host-guest complexation.
• Targeted cancer chemotherapy requires strategies to enhance efficacy and reduce side effects.

Purpose of the Study:

• To develop a water-soluble supramolecular polymer for chemotherapy.
• To encapsulate the anticancer drug oxaliplatin into the polymer.
• To investigate the targeted drug release and enhanced cytotoxicity in cancer cells.

Main Methods:

• Synthesis of a main-chain cucurbit[7]uril (CB[7]) based polymer (poly-CB[7]) via click chemistry.
• Encapsulation of oxaliplatin into the poly-CB[7] supramolecular complex.
• In vitro evaluation of cytotoxicity in normal and cancer cells (colorectal cancer).
• Assessment of drug release mechanism triggered by spermine competition.

Main Results:

• The poly-CB[7]-oxaliplatin complex showed low cytotoxicity to normal cells.
• Spermine overexpressed in cancer cells triggered competitive release of oxaliplatin, restoring cytotoxicity.
• The supramolecular polymeric complex exhibited higher cytotoxicity to cancer cells than free oxaliplatin.
• The complex demonstrated improved in vivo circulation time compared to simpler supramolecular complexes.

Conclusions:

• Supramolecular polymeric chemotherapy using CB[7]-based polymers is a promising strategy.
• Targeted drug release and enhanced efficacy are achieved through host-guest interactions and competitive displacement.
• This approach offers potential for improved cancer treatment with reduced systemic toxicity.