Novel Aptamer-Drug Conjugate for Targeted Therapy in Triple-Negative Breast Cancer

Area of Science:

• Biochemistry
• Oncology
• Molecular Biology

Background:

• Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its aggressive nature and lack of targeted therapies.
• Nucleic acid aptamers offer potential as highly specific targeting agents in cancer therapy.

Purpose of the Study:

• To identify and characterize aptamers that specifically target and internalize into TNBC cells.
• To develop an aptamer-drug conjugate (ApDC) for targeted delivery of cytotoxic agents to TNBC.

Main Methods:

• Identification of a chemically modified aptamer (AptT1) with high affinity and specificity for TNBC cells.
• Investigation of the internalization mechanism, identifying Annexin A2 (ANXA2) and clathrin-mediated endocytosis as key factors.
• Construction and in vivo evaluation of an AptT1-SN38 conjugate (ApDC) in a TNBC xenograft model.

Main Results:

• AptT1 demonstrated specific recognition and internalization into TNBC cells.
• ANXA2 was confirmed as crucial for AptT1 uptake via clathrin-mediated endocytosis.
• The AptT1-based ApDC exhibited significant anti-tumor efficacy and favorable safety profiles in preclinical TNBC models.

Conclusions:

• AptT1 is a promising targeting agent for TNBC.
• AptT1-based ApDC represents a potential innovative targeted therapeutic strategy for TNBC, warranting further clinical investigation.