Theranostics 2019; 9(3):884-899. doi:10.7150/thno.29445 This issue Cite

Research Paper

Nanoparticle Binding to Urokinase Receptor on Cancer Cell Surface Triggers Nanoparticle Disintegration and Cargo Release

Shijie Li1,2, Cai Yuan1, Jincan Chen2, Dan Chen1, Zhuo Chen2, Wenlie Chen3, Shufeng Yan2, Ping Hu2, Jinping Xue1, Rui Li2, Ke Zheng1✉, Mingdong Huang1✉

1. Fuzhou University, Fuzhou, Fujian 350116, China.
2. State Key Laboratory of Structure Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.
3. Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.

Citation:
Li S, Yuan C, Chen J, Chen D, Chen Z, Chen W, Yan S, Hu P, Xue J, Li R, Zheng K, Huang M. Nanoparticle Binding to Urokinase Receptor on Cancer Cell Surface Triggers Nanoparticle Disintegration and Cargo Release. Theranostics 2019; 9(3):884-899. doi:10.7150/thno.29445. https://www.thno.org/v09p0884.htm
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Abstract

Graphic abstract

Cancer cell expresses abundant surface receptors. These receptors are important targets for cancer treatment and imaging applications. Our goal here is to develop nanoparticles with cargo loading and tumor targeting capability.

Methods: A peptide targeting at cancer cell surface receptor (urokinase receptor, uPAR) was expressed in fusion with albumin (diameter of ~7 nm), and the fusion protein was assembled into nanoparticles with diameter of 40 nm, either in the presence or absence of cargo molecules, by a novel preparation method. An important feature of this method is that the nanoparticles were stabilized by hydrophobic interaction of the fusion protein and no covalent linking agent was used in the preparation. The stability, the cargo release, in vitro and in vivo properties of such formed nanoparticles were characterized by transmission electron microscopy, dynamic light scattering, gel shift assay, laser scanning confocal microscopy and 3D fluorescent molecular tomography.

Results: The nanoparticles were stable for more than two weeks in aqueous buffer, even in the buffer containing 10% fetal bovine serum. Interestingly, in the presence of urokinase receptor, the uPAR-targeting nanoparticle disintegrated into 7.5 nm fragments and released its cargo, but not the non-targeting nanoparticles made from albumin by the same preparation method. Such nanoparticles also showed higher uptake and cytotoxicity to the receptor-expressing cancer cells in vitro and higher tumor accumulation in xenografted tumor-bearing mice in vivo compared to the non-targeting nanoparticles.

Conclusion: Our results demonstrate a new function of cell surface receptor as a responsive trigger to disassemble nanoparticles, besides its common use to enrich targeting agents. Such nanoparticles were thus named receptor-responsive nanoparticles (RRNP).

Keywords: receptor-triggered disintegration, cargo release, urokinase receptor, amino terminal fragment of urokinase-type plasminogen activator, human serum albumin


Citation styles

APA
Li, S., Yuan, C., Chen, J., Chen, D., Chen, Z., Chen, W., Yan, S., Hu, P., Xue, J., Li, R., Zheng, K., Huang, M. (2019). Nanoparticle Binding to Urokinase Receptor on Cancer Cell Surface Triggers Nanoparticle Disintegration and Cargo Release. Theranostics, 9(3), 884-899. https://doi.org/10.7150/thno.29445.

ACS
Li, S.; Yuan, C.; Chen, J.; Chen, D.; Chen, Z.; Chen, W.; Yan, S.; Hu, P.; Xue, J.; Li, R.; Zheng, K.; Huang, M. Nanoparticle Binding to Urokinase Receptor on Cancer Cell Surface Triggers Nanoparticle Disintegration and Cargo Release. Theranostics 2019, 9 (3), 884-899. DOI: 10.7150/thno.29445.

NLM
Li S, Yuan C, Chen J, Chen D, Chen Z, Chen W, Yan S, Hu P, Xue J, Li R, Zheng K, Huang M. Nanoparticle Binding to Urokinase Receptor on Cancer Cell Surface Triggers Nanoparticle Disintegration and Cargo Release. Theranostics 2019; 9(3):884-899. doi:10.7150/thno.29445. https://www.thno.org/v09p0884.htm

CSE
Li S, Yuan C, Chen J, Chen D, Chen Z, Chen W, Yan S, Hu P, Xue J, Li R, Zheng K, Huang M. 2019. Nanoparticle Binding to Urokinase Receptor on Cancer Cell Surface Triggers Nanoparticle Disintegration and Cargo Release. Theranostics. 9(3):884-899.

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