KEY TAKEAWAYS
- The study aimed to explore a precision therapy strategy for pts with TNBC.
- The Fluorouracil-modified AS1411-paclitaxel conjugates showed promising TNBC targeting and synergistic antitumor effects, needing translational investigations.
Triple-negative breast cancer (TNBC) is a recurrent, heterogeneous, and invasive form of breast cancer. The treatment of patients (pts) with TNBC sequentially using paclitaxel and fluorouracil has shown promising outcomes. However, the sequential administration of these chemotherapeutic agents is quite challenging.
Yuan Ma and the team aimed to explore a precision therapy strategy for TNBC through the sequential delivery of paclitaxel and fluorouracil.
Researchers developed a dual chemo-loaded aptamer featuring redox-sensitive caged paclitaxel for rapid release and non-cleavable caged fluorouracil for slow release. The binding affinity to the target protein was validated using enzyme-linked oligonucleotide and surface plasmon resonance assays.
The targeting and internalization of tumors were confirmed through flow cytometry and confocal microscopy assays. The inhibitory effects on TNBC progression were evaluated via pharmacological studies in vitro and in vivo.
The results indicated that various redox-responsive aptamer-paclitaxel conjugates were synthesized. Among them, the AS1411-paclitaxel conjugate with a thioether linker (ASP) exhibited high anti-proliferation ability against TNBC cells, and its targeting ability was further improved through fluorouracil modification.
The fluorouracil-modified AS1411-paclitaxel conjugate with a thioether linker (FASP) exhibited effective targeting of TNBC cells and significantly improved the inhibitory effects on TNBC progression in vitro and in vivo.
The study successfully developed fluorouracil-modified AS1411-paclitaxel conjugates with a thioether linker for targeted combination chemotherapy in TNBC. It concluded that fluorouracil-modified AS1411-paclitaxel conjugates offered targeted chemotherapy in pts withTNBC, resulting in synergistic antitumor effects and declined toxicity in vivo. Exploring the challenges in stability, immunogenicity, and scalability is suggested for advancing the clinical applications.
This study was supported by the Guangdong Basic and Applied Basic Research Foundation , the National Key R&D Program of China, Theme-based Research Scheme , Interdisciplinary Research Clusters Matching Scheme of Hong Kong Baptist University, Guangdong-Hong Kong Technology Cooperation Funding Scheme , Key-Area R&D Program of Department of Science and Technology of Hunan Province , and Science and Technology Innovation Commission of Shenzhen Municipality Funds.
Source: https://pubmed.ncbi.nlm.nih.gov/38951906/
Ma Y., Xie D., Chen Z., et al. (2024). “Advancing targeted combination chemotherapy in triple negative breast cancer: nucleolin aptamer-mediated controlled drug release.” J Transl Med. 2024 Jul 1;22(1):604. doi: 10.1186/s12967-024-05429-8. PMID: 38951906.
