A selective RCC1 inhibitor loaded in membrane-coated DNA nanocage for targeted suppression of TNBC progression

Area of Science:

• Oncology
• Biomedical Engineering
• Molecular Biology

Background:

• Triple-negative breast cancer (TNBC) has a high recurrence rate and poor prognosis due to a lack of effective targeted therapies.
• RCC1 is highly expressed in TNBC, correlating with poor prognosis by promoting tumor progression via Notch1 signaling.
• Identifying novel therapeutic targets and delivery systems is crucial for improving TNBC treatment outcomes.

Purpose of the Study:

• To investigate RCC1 as a potential therapeutic target for TNBC.
• To identify small-molecule inhibitors of RCC1.
• To develop an advanced nanodrug delivery system for enhanced TNBC therapy.

Main Methods:

• High-throughput screening identified Euphorbiasteroid (Ebd) as an RCC1 inhibitor.
• A biomimetic nanodrug delivery system (TPRDN) was engineered using tetrahedral DNA nanocages.
• TPRDN was coated with hybrid cell membranes (TNBC, platelet, red blood cell) and functionalized with a Nectin-4 targeting peptide.

Main Results:

• Ebd significantly suppressed TNBC tumor growth and metastasis in preclinical models.
• The TPRDN system demonstrated enhanced targeting of TNBC tissues and circulating tumor cells.
• The nanodrug delivery system improved the efficacy of Ebd, overcoming its bioavailability and off-target limitations.

Conclusions:

• RCC1 is a promising therapeutic target for TNBC.
• The developed biomimetic nanodrug delivery system (TPRDN) offers a precise and effective strategy for TNBC treatment.
• This approach holds potential for improving outcomes in patients with triple-negative breast cancer.