Theranostics 2023; 13(7):2140-2153. doi:10.7150/thno.82140 This issue Cite

Research Paper

Supramolecular nanofibers co-loaded with dabrafenib and doxorubicin for targeted and synergistic therapy of differentiated thyroid carcinoma

Peng Chen1, Xiaoyao Cai2, Ganen Mu2, Yuansheng Duan1, Chao Jing1, Zhimou Yang3, Cuihong Yang2,✉, Xudong Wang1,✉

1. Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
2. Key Laboratory of Radiopharmacokinetics for Innovative Drugs, Chinese Academy of Medical Sciences, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China.
3. State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering, and National Institute of Functional Materials, Nankai University, Tianjin 300071, China.

Citation:
Chen P, Cai X, Mu G, Duan Y, Jing C, Yang Z, Yang C, Wang X. Supramolecular nanofibers co-loaded with dabrafenib and doxorubicin for targeted and synergistic therapy of differentiated thyroid carcinoma. Theranostics 2023; 13(7):2140-2153. doi:10.7150/thno.82140. https://www.thno.org/v13p2140.htm
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Abstract

Graphic abstract

Rationale: Although surgery, radioiodine therapy, and thyroid hormone therapy are the primary clinical treatments for differentiated thyroid carcinoma (DTC), effective therapy for locally advanced or progressive DTC remains challenging. BRAF V600E, the most common BRAF mutation subtype, is highly related to DTC. Previous studies prove that combination of kinase inhibitors and chemotherapeutic drugs may be a potential approach for DTC treatment. In this study, a supramolecular peptide nanofiber (SPNs) co-loaded with dabrafenib (Da) and doxorubicin (Dox) was constructed for targeted and synergistic therapy with BRAF V600E+ DTC.

Methods: A self-assembling peptide nanofiber (Biotin-GDFDFDYGRGD, termed SPNs) bearing biotin at the N-terminus and a cancer-targeting ligand RGD at the C-terminus was used as a carrier for co-loading Da and Dox. D-phenylalanine and D-tyrosine (DFDFDY) are used to improve the stability of peptides in vivo. Under multiple non-covalent interactions, SPNs/Da/Dox assembled into longer and denser nanofibers. RGD ligand endows self-assembled nanofibers with targeting cancer cells and co-delivery, thereby improving cellular uptake of payloads.

Results: Both Da and Dox indicated decreased IC50 values upon encapsulation in SPNs. Co-delivery of Da and Dox by SPNs exhibited the strongest therapeutic effect in vitro and in vivo by inhibiting ERK phosphorylation in BRAF V600E mutant thyroid cancer cells. Moreover, SPNs enable efficient drug delivery and lower Dox dosage, thereby significantly reducing its side effects.

Conclusion: This study proposes a promising paradigm for the synergistic treatment of DTC with Da and Dox using supramolecular self-assembled peptides as carriers.

Keywords: supramolecular self-assembly, differentiated thyroid carcinoma, doxorubicin, dabrafenib, BRAF V600E


Citation styles

APA
Chen, P., Cai, X., Mu, G., Duan, Y., Jing, C., Yang, Z., Yang, C., Wang, X. (2023). Supramolecular nanofibers co-loaded with dabrafenib and doxorubicin for targeted and synergistic therapy of differentiated thyroid carcinoma. Theranostics, 13(7), 2140-2153. https://doi.org/10.7150/thno.82140.

ACS
Chen, P.; Cai, X.; Mu, G.; Duan, Y.; Jing, C.; Yang, Z.; Yang, C.; Wang, X. Supramolecular nanofibers co-loaded with dabrafenib and doxorubicin for targeted and synergistic therapy of differentiated thyroid carcinoma. Theranostics 2023, 13 (7), 2140-2153. DOI: 10.7150/thno.82140.

NLM
Chen P, Cai X, Mu G, Duan Y, Jing C, Yang Z, Yang C, Wang X. Supramolecular nanofibers co-loaded with dabrafenib and doxorubicin for targeted and synergistic therapy of differentiated thyroid carcinoma. Theranostics 2023; 13(7):2140-2153. doi:10.7150/thno.82140. https://www.thno.org/v13p2140.htm

CSE
Chen P, Cai X, Mu G, Duan Y, Jing C, Yang Z, Yang C, Wang X. 2023. Supramolecular nanofibers co-loaded with dabrafenib and doxorubicin for targeted and synergistic therapy of differentiated thyroid carcinoma. Theranostics. 13(7):2140-2153.

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