Balancing Chemical and Supramolecular Stability in OEGylated Supramolecular Polymers for Systemic Drug Delivery

Area of Science:

• Polymer Chemistry
• Supramolecular Chemistry
• Drug Delivery Systems

Background:

• Poly(ethylene glycol) (PEG)ylation enhances drug properties but supramolecular approaches offer new possibilities.
• Hydrophobic anticancer drugs like camptothecin (CPT) require improved delivery systems.
• Self-assembly of modified drugs into nanostructures can improve therapeutic outcomes.

Purpose of the Study:

• To develop novel supramolecular polymeric prodrugs (SPDs) of CPT using oligo(ethylene glycol) (OEG).
• To investigate the impact of linker chemical stability on CPT release kinetics and SPD performance.
• To evaluate the in vitro and in vivo antitumor efficacy of OEGylated CPT-based SPs.

Main Methods:

• Synthesis of OEGylated CPT prodrugs with varying biodegradable linkers (e.g., etcSS, buSS).
• Characterization of self-assembled supramolecular polymer (SP) morphology and drug release profiles.
• In vitro cytotoxicity assays and in vivo studies in colon cancer models comparing SPs to irinotecan.

Main Results:

• OEGylated CPT spontaneously formed tubular SPs with a surface OEG coating.
• SPs with a faster-releasing etcSS linker demonstrated superior potency and antitumor efficacy compared to buSS linkers.
• Tubustecan (TT) 1E and TT 7E SPs showed enhanced tumor growth inhibition and prolonged survival versus irinotecan in vivo.

Conclusions:

• Supramolecular OEGylation is a viable strategy for engineering advanced drug-based SPs.
• Controlling chemical linker stability is crucial for optimizing drug release and therapeutic efficacy.
• The developed SPs hold significant promise as potent anticancer therapeutics, particularly for colon cancer.