Theranostics 2021; 11(5):2475-2489. doi:10.7150/thno.52076 This issue Cite

Research Paper

Co-delivery of 5-fluorouracil and miRNA-34a mimics by host-guest self-assembly nanocarriers for efficacious targeted therapy in colorectal cancer patient-derived tumor xenografts

Jianbin Xu1, Guolin Zhang1, Xin Luo1, Di Wang1, Wei Zhou1, Yan Zhang2, Wei Zhang1, Jiaxin Chen1, Qing Meng1, Engeng Chen1, Heng Chen3✉, Zhangfa Song1✉

1. Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, P.R. China.
2. State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300350, P.R. China.
3. Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen 518060, P.R. China.

Citation:
Xu J, Zhang G, Luo X, Wang D, Zhou W, Zhang Y, Zhang W, Chen J, Meng Q, Chen E, Chen H, Song Z. Co-delivery of 5-fluorouracil and miRNA-34a mimics by host-guest self-assembly nanocarriers for efficacious targeted therapy in colorectal cancer patient-derived tumor xenografts. Theranostics 2021; 11(5):2475-2489. doi:10.7150/thno.52076. https://www.thno.org/v11p2475.htm
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Abstract

Graphic abstract

Rationale: A co-delivery system that can transport chemotherapeutic drugs and nucleotide drugs to distinct targets in tumors is an attractive strategy for cancer therapy. In this study, well-defined targeted quantum dot (QD)-based multifunctional nanocarriers were developed through self-assembly driven by host-guest interactions. 5-fluorouracil (5-FU) and microRNA-34a mimics (miR-34a(m)) were co-administered to achieve synergistic effects for colorectal cancer (CRC) therapy for the first time. Furthermore, the CRC patient-derived tumor xenograft (PDX) model, which closely mimics human CRC tumor pathological properties, was used for evaluating the therapeutic effect in this research.

Methods: Multiple β-cyclodextrin (CD)-attached QD nanoparticles were used as host molecules. An adamantane (ADA)-modified TCP1 peptide-targeting ligand (TCP1) was used as the guest molecule. 5-FU and miR-34a(m) were loaded into TCP1-CD-QD nanocarriers, which were used to treat CRC in vitro and in vivo. In addition, the CRC PDX model was used to evaluate the treatment efficacy of this co-delivery system.

Results: 5-FU and miR-34a(m) can be efficiently encapsulated into TCP1-CD-QD nanocarriers and delivered into CRC cells, which led to the inhibition of the proliferation and migration of CRC cells in vitro and suppression of tumor growth in a CRC cell-derived tumor xenograft model. The obtained data further suggested that co-delivery of 5-FU and miR-34a(m) could achieve synergistic effects for CRC therapy. Notably, targeted therapy via the co-delivery of 5-FU and miR-34a(m) by TCP1-CD-QD nanocarriers significantly inhibited the growth of PDX tumors.

Conclusions: These studies strongly indicate that such a nanocarrier-based co-delivery system is a promising combined therapeutic strategy that utilizes chemotherapeutic drugs and nucleotide drugs for enhancing colorectal cancer targeting and synergistic therapy.

Keywords: co-delivery, PDX model, targeted therapy, synergistic therapy


Citation styles

APA
Xu, J., Zhang, G., Luo, X., Wang, D., Zhou, W., Zhang, Y., Zhang, W., Chen, J., Meng, Q., Chen, E., Chen, H., Song, Z. (2021). Co-delivery of 5-fluorouracil and miRNA-34a mimics by host-guest self-assembly nanocarriers for efficacious targeted therapy in colorectal cancer patient-derived tumor xenografts. Theranostics, 11(5), 2475-2489. https://doi.org/10.7150/thno.52076.

ACS
Xu, J.; Zhang, G.; Luo, X.; Wang, D.; Zhou, W.; Zhang, Y.; Zhang, W.; Chen, J.; Meng, Q.; Chen, E.; Chen, H.; Song, Z. Co-delivery of 5-fluorouracil and miRNA-34a mimics by host-guest self-assembly nanocarriers for efficacious targeted therapy in colorectal cancer patient-derived tumor xenografts. Theranostics 2021, 11 (5), 2475-2489. DOI: 10.7150/thno.52076.

NLM
Xu J, Zhang G, Luo X, Wang D, Zhou W, Zhang Y, Zhang W, Chen J, Meng Q, Chen E, Chen H, Song Z. Co-delivery of 5-fluorouracil and miRNA-34a mimics by host-guest self-assembly nanocarriers for efficacious targeted therapy in colorectal cancer patient-derived tumor xenografts. Theranostics 2021; 11(5):2475-2489. doi:10.7150/thno.52076. https://www.thno.org/v11p2475.htm

CSE
Xu J, Zhang G, Luo X, Wang D, Zhou W, Zhang Y, Zhang W, Chen J, Meng Q, Chen E, Chen H, Song Z. 2021. Co-delivery of 5-fluorouracil and miRNA-34a mimics by host-guest self-assembly nanocarriers for efficacious targeted therapy in colorectal cancer patient-derived tumor xenografts. Theranostics. 11(5):2475-2489.

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