Enzymatically Transformable Polymersome-Based Nanotherapeutics to Eliminate Minimal Relapsable Cancer

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Preventing cancer recurrence after surgery is challenging due to residual tumor cells.
• Effective drug delivery to minimal residual tumors and the premetastatic niche is limited.

Purpose of the Study:

• To develop a nanotherapeutic strategy for preventing postsurgical cancer recurrence.
• To exploit matrix metalloproteinase (MMP) activity for targeted drug delivery.

Main Methods:

• An enzymatically transformable polymer-based nanotherapeutic system was designed.
• The system codelivers colchicine and marimastat, activated by MMPs.
• DePEGylation by MMPs enhances tissue targeting and differential drug release.

Main Results:

• The nanotherapeutic demonstrated improved bioavailability and retention in tumor-associated tissues.
• Differential release of drugs targeted extracellular MMPs and intracellular microtubules.
• Successful disruption of the premetastatic niche and elimination of microresiduals post-surgery.

Conclusions:

• This nanotherapeutic approach significantly reduces metastatic and local-regional cancer recurrence.
• The strategy offers a potential therapeutic window for colchicine and MMP inhibitors in inflammatory disorders.