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Aptamer-Peptide Conjugates as Targeted Chemosensitizers for Breast Cancer Treatment
Yan Tan1, Yingying Li1, Yi-Xin Qu1
1Molecular Sciences and Biomedicine Laboratory (MBL), State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, and Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, P. R. China.
Abstract:
High levels of heat shock protein 70 (HSP70) in tumors are commonly associated with poor prognosis, enhanced doxorubicin (DOX)-induced cardiotoxicity, and even drug resistance in DOX-related cancer chemotherapy. Several peptides possess remarkable protein inhibition and chemosensitization effects, which are attributed to their specific targeting ability against HSP70. However, the inherent poor cell penetration capacity considerably restricts the biomedical applications of these peptides. We herein describe the design and development of anti-MUC1 aptamer-peptide conjugates (ApPCs) as targeted chemosensitizers to overcome the above-mentioned issues. Moreover, DOX could be loaded on the ApPC to deliver the DOX-enclosed agent ApPC-DOX, which simultaneously acts as a targeted chemosensitizer and anticancer agent for combating drug resistance in breast cancer therapy. This innovative, engineered biocompatible conjugate not only enhances the sensitivity of DOX-resistant cells but also alleviates cardiotoxicity of DOX in vivo, highlighting the success of this targeted chemosensitizer strategy.
Insights
This study developed targeted chemosensitizers using anti-MUC1 aptamer-peptide conjugates (ApPCs) to overcome drug resistance and reduce doxorubicin (DOX) cardiotoxicity in cancer therapy.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- High heat shock protein 70 (HSP70) levels correlate with poor cancer prognosis, doxorubicin (DOX) cardiotoxicity, and drug resistance.
- Peptides targeting HSP70 show promise for protein inhibition and chemosensitization but suffer from poor cell penetration.
Purpose of the Study:
- To design and develop anti-MUC1 aptamer-peptide conjugates (ApPCs) as targeted chemosensitizers.
- To overcome the limitations of poor cell penetration and enhance the efficacy of DOX-based cancer therapy.
Main Methods:
- Conjugation of anti-MUC1 aptamers with peptides targeting HSP70 to create ApPCs.
- Loading DOX onto ApPCs to form ApPC-DOX for simultaneous targeted chemosensitization and anticancer drug delivery.
Main Results:
- The developed ApPC-DOX conjugate enhanced the sensitivity of DOX-resistant cancer cells.
- The ApPC-DOX conjugate effectively alleviated doxorubicin-induced cardiotoxicity in vivo.
Conclusions:
- Engineered biocompatible conjugates offer a successful strategy for targeted chemosensitization.
- This approach holds potential for combating drug resistance and reducing cardiotoxicity in breast cancer therapy.
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