Multicyclic topology-enhanced anticancer drug delivery

Area of Science:

• Polymer Chemistry
• Materials Science
• Biomedical Engineering

Background:

• Nature utilizes precision and self-assembly for complex structures from amino acids.
• Single cyclic polymers (SCPs) offer advantages over linear polymers.
• Multicyclic polymers (MCPs) are hypothesized to provide enhanced properties but lack efficient synthesis methods.

Purpose of the Study:

• To develop a straightforward and robust strategy for synthesizing multicyclic polymers (MCPs) with controllable valency.
• To create biocompatible MCPs based on oligo(ethylene glycol) (OEG) and cyclic poly(ε-caprolactone) (cPCL).
• To evaluate the potential of MCPs as drug delivery vehicles for enhanced biomedical applications.

Main Methods:

• Facile one-pot statistical reversible addition-fragmentation chain transfer (RAFT) copolymerization for MCP synthesis.
• Synthesis of biocompatible MCPs using OEG and cPCL.
• Self-assembly of MCPs into nanostructures for drug delivery applications.

Main Results:

• Successful synthesis of MCPs with controllable valency via one-pot RAFT copolymerization.
• MCPs self-assembled into well-defined nanostructures.
• MCP-based drug delivery systems exhibited enhanced colloidal stability, low critical micelle concentration (CMC) of 80.3 nM, increased drug loading, cellular uptake, tumor accumulation, and anti-tumor efficacy in vivo compared to SCP analogues.

Conclusions:

• A facile and robust strategy for synthesizing MCPs with tunable valency has been established.
• Multicyclic topology significantly enhances anti-cancer efficiency in vivo compared to single cyclic topologies.
• This work provides key technologies and concepts for the development of cyclic topology-derived biomaterials for biomedical applications.