Cascade Enzymes Confined in DNA Nanoanchors for Antitumor Therapy

Area of Science:

• Biotechnology
• Nanomedicine
• Cancer Therapy

Background:

• Cascade-enzyme systems show promise for tumor treatment by converting nutrients into toxins.
• Challenges include poor enzyme retention and extratumoral toxicity, limiting therapeutic efficacy.

Purpose of the Study:

• To develop a spatially confined cascade enzyme system using cell membrane-DNA nanoanchors (DNANA) for enhanced in vivo tumor therapy.
• To improve enzyme localization and reduce off-target toxicity in cancer treatment.

Main Methods:

• Constructed DNANAs using cholesterol-labeled DNA triangular prisms for stable cell membrane attachment.
• Confined glucose oxidase (GOx) and horseradish peroxidase (HRP) enzymes to biotin-labeled DNANAs via streptavidin modification.
• Administered DNANAs intratumorally to achieve localized enzyme colonization and minimize leakage.

Main Results:

• DNANA enzymes demonstrated efficient tumor site colonization via cellular membrane engineering.
• Significantly reduced off-target enzyme leakage and associated extratumoral toxicity.
• Achieved effective in vitro and in vivo cancer therapy by depleting tumor glucose and generating cytotoxic hydroxyl radicals.

Conclusions:

• The membrane-engineered DNANA system offers a novel approach for localized tumor treatment.
• Spatially confined cascade enzymes can improve therapeutic efficacy and safety in cancer therapy.
• This strategy presents a conceptual advancement in nanomedicine for malignant tumor treatment.