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Anti-nucleolin Aptamer as a Boom in Rehabilitation of Breast Cancer
S K Janani1, S P Dhanabal2, Raman Sureshkumar1
1Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India.
Abstract:
Breast cancer is the second leading cause of cancer-related deaths. It is important to target the complex pathways using a suitable targeted delivery system. Targeted delivery systems can effectively act on cancer cells and lead to the annihilation of tumor proliferation. They mainly employ targeting agents like aptamers linked to the formulation. Based on the expression of the receptors on the surface of the cancer cells, suitable aptamers can be developed. AS1411 is one such aptamer that has the ability to bind to the over-expressed nucleolin present in breast cancer cells. Nucleolin is a phosphoprotein that is involved in various aspects, like cell growth, differentiation and survival. Mostly they are found in the nucleolus, nucleus, cytoplasm and cell surface. The shuttling effect of the nucleolin between the nucleus and cytoplasm serves as a bonus for the AS1411 aptamer. Because of the shutting effect, the internalization of the drug compound or chemotherapeutic drug inside the cell can be achieved. In this article, we have discussed nucleolin, anti-nucleolin aptamer, namely, AS1411, and its application in exhibiting various anticancer activities, including apoptosis, anti-angiogenesis, anti-metastasis, stimulation of tumor suppressor (i.e., P53), and inhibition of tumor inducer. Further, the ways of internalization, namely macropinocytosis, are also discussed. Additionally, we have also discussed the superiority of the aptamer compared to the antibodies as well as the limitations of the aptamers. By considering all the above parameters, we hope this aptamer will be effective in the management and eradication of breast cancer cells.
Insights
The AS1411 aptamer targets nucleolin on breast cancer cells, offering a novel approach for targeted delivery and potentially eradicating tumors through mechanisms like apoptosis and anti-angiogenesis.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Breast cancer is a leading cause of cancer mortality, necessitating advanced targeted delivery systems.
- Targeted delivery systems utilize agents like aptamers to specifically interact with cancer cells.
- Aptamers can be designed to target receptors overexpressed on cancer cell surfaces.
Purpose of the Study:
- To discuss nucleolin as a target in breast cancer.
- To explore the anti-cancer activities of the AS1411 aptamer against nucleolin.
- To examine the internalization mechanisms and advantages of aptamers over antibodies.
Main Methods:
- Review of literature on nucleolin, AS1411 aptamer, and breast cancer pathways.
- Discussion of aptamer-mediated drug delivery and internalization processes (e.g., macropinocytosis).
- Comparative analysis of aptamers versus antibodies for targeted cancer therapy.
Main Results:
- AS1411 aptamer binds to overexpressed nucleolin in breast cancer cells.
- Nucleolin's shuttling between nucleus and cytoplasm facilitates AS1411 internalization.
- AS1411 exhibits anticancer activities including apoptosis, anti-angiogenesis, and anti-metastasis.
Conclusions:
- AS1411 demonstrates significant potential in managing and eradicating breast cancer cells.
- The aptamer's ability to stimulate tumor suppressors (P53) and inhibit tumor inducers is highlighted.
- AS1411 offers advantages over antibodies, with discussed limitations.
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