Collagenase IV and clusterin-modified polycaprolactone-polyethylene glycol nanoparticles for penetrating dense tumor tissues

Huang, Hao-Yan; Chen, Li-Qing; Sun, Wei; Du, Huan-Huan; Dong, Shunli; Ahmed, Atef Mohammed Qasem; Cao, Dingyun; Cui, Jing-Hao; Zhang, Yi; Cao, Qing-Ri

doi:10.7150/thno.47446

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Nanotheranostics 2024; 8(3): 380-400. [Abstract] [Full text] [PDF]

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Theranostics 2021; 11(2):906-924. doi:10.7150/thno.47446 This issue Cite

Research Paper

Collagenase IV and clusterin-modified polycaprolactone-polyethylene glycol nanoparticles for penetrating dense tumor tissues

Hao-Yan Huang^1,*, Li-Qing Chen^1,*, Wei Sun¹, Huan-Huan Du¹, Shunli Dong¹, Atef Mohammed Qasem Ahmed¹, Dingyun Cao², Jing-Hao Cui¹, Yi Zhang^1,✉, Qing-Ri Cao^1,✉

1. College of Pharmaceutical Sciences, Soochow University, Jiangsu Province, Suzhou 215123, People's Republic of China
2. Suzhou No3 high school sino-us course center, Jiangsu Province, Suzhou 215001, People's Republic of China
^* These authors contributed equally to this work.

Citation:

Huang HY, Chen LQ, Sun W, Du HH, Dong S, Ahmed AMQ, Cao D, Cui JH, Zhang Y, Cao QR. Collagenase IV and clusterin-modified polycaprolactone-polyethylene glycol nanoparticles for penetrating dense tumor tissues. Theranostics 2021; 11(2):906-924. doi:10.7150/thno.47446. https://www.thno.org/v11p0906.htm

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Abstract

Purpose: Novel collagenase IV (ColIV) and clusterin (CLU)-modified polycaprolactone-polyethylene glycol (PCL-PEG) nanoparticles that load doxorubicin (DOX) were designed and fully evaluated in vitro and in vivo.

Methods: PCL-PEG-ColIV was synthesized by linking PCL-PEG and ColIV through a carbodiimide method. DOX-loaded nanoparticles (DOX-PCL-PEG-ColIV) were self-assembly prepared, followed by noncovalently adsorbing CLU on the DOX-PCL-PEG-ColIV surface to obtain DOX-PCL-PEG-ColIV /CLU nanoparticles, which can penetrate through the tumor extracellular matrix (ECM) and inhibit phagocytosis by macrophage. The physicochemical properties of nanoparticles were characterized. The cellular uptake and antiphagocytosis ability of nanoparticles in MCF-7 tumor cells and RAW264.7 cells were investigated. The penetration ability of nanoparticles was individually evaluated in the two-dimensional (2D) and three-dimensional (3D) ECM models. The tissue distribution and antitumor effect of nanoparticles were evaluated in MCF-7 cell-bearing nude mice.

Results: Compared with DOX-PCL-PEG-COOH nanoparticles, DOX-PCL-PEG-ColIV/CLU nanoparticles could effectively overcome the phagocytosis by RAW264.7 and showed excellent cellular uptake in MCF-7 cells. In addition, they showed remarkable penetration ability through the 2D and 3D ECM models. DOX-PCL-PEG-ColIV/CLU nanoparticles significantly reduced the drug distribution in the liver and spleen and enhanced the drug accumulation in tumor tissue compared with DOX-PCL-PEG-COOH or DOX-PCL-PEG-ColIV nanoparticles. DOX-PCL-PEG-ColIV/CLU nanoparticles showed remarkable antitumor effect but did not cause severe pathological damages in the main tissues, including the heart, liver, spleen, lung, and kidney.

Conclusion: Novel ColIV and CLU-modified PCL-PEG nanoparticles showed excellent cellular uptake, ECM penetration, antiphagocytosis, and antitumor effects both in vitro and in vivo.

Keywords: extracellular matrix, collagenase IV, clusterin, PCL-PEG nanoparticles, doxorubicin

Citation styles

APA

Huang, H.Y., Chen, L.Q., Sun, W., Du, H.H., Dong, S., Ahmed, A.M.Q., Cao, D., Cui, J.H., Zhang, Y., Cao, Q.R. (2021). Collagenase IV and clusterin-modified polycaprolactone-polyethylene glycol nanoparticles for penetrating dense tumor tissues. Theranostics, 11(2), 906-924. https://doi.org/10.7150/thno.47446.

ACS

Huang, H.Y.; Chen, L.Q.; Sun, W.; Du, H.H.; Dong, S.; Ahmed, A.M.Q.; Cao, D.; Cui, J.H.; Zhang, Y.; Cao, Q.R. Collagenase IV and clusterin-modified polycaprolactone-polyethylene glycol nanoparticles for penetrating dense tumor tissues. Theranostics 2021, 11 (2), 906-924. DOI: 10.7150/thno.47446.

NLM

CSE

Huang HY, Chen LQ, Sun W, Du HH, Dong S, Ahmed AMQ, Cao D, Cui JH, Zhang Y, Cao QR. 2021. Collagenase IV and clusterin-modified polycaprolactone-polyethylene glycol nanoparticles for penetrating dense tumor tissues. Theranostics. 11(2):906-924.

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