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Open Access Research article

Small-sized polymeric micelles incorporating docetaxel suppress distant metastases in the clinically-relevant 4T1 mouse breast cancer model

Yunfei Li12, Mingji Jin1, Shuai Shao13, Wei Huang1, Feifei Yang1, Wei Chen1, Shenghua Zhang2, Guimin Xia2 and Zhonggao Gao1*

Author Affiliations

1 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, 1 Xiannongtan Street, Beijing 100050, PR China

2 Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, PR China

3 Pharmacy School, Yanbian University, Yanji 133000, PR China

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BMC Cancer 2014, 14:329  doi:10.1186/1471-2407-14-329

Published: 10 May 2014

Abstract

Background

The small size of ultra-small nanoparticles makes them suitable for lymphatic delivery, and many recent studies have examined their role in anti-metastasis therapy. However, the anti-metastatic efficacy of small-sized nanocarriers loaded with taxanes such as docetaxel has not yet been investigated in malignant breast cancer.

Methods

We encapsulated docetaxel using poly(D,L-lactide)1300-b-(polyethylene glycol-methoxy)2000 (mPEG2000-b-PDLLA1300) to construct polymeric micelles with a mean diameter of 16.76 nm (SPM). Patient-like 4T1/4T1luc breast cancer models in Balb/c mice, with resected and unresected primary tumors, were used to compare the therapeutic efficacies of SPM and free docetaxel (Duopafei) against breast cancer metastasis using bioluminescent imaging, lung nodule examination, and histological examination.

Result

SPM showed similar efficacy to Duopafei in terms of growth suppression of primary tumors, but greater chemotherapeutic efficacy against breast cancer metastasis. In addition, lung tissue inflammation was decreased in the SPM-treated group, while many tumor cells and neutrophils were found in the Duopafei-treated group.

Conclusion

Small-sized mPEG2000-b-PDLLA1300 micelles could provide an enhanced method of docetaxel delivery in breast cancer metastasis, and may represent a valid chemotherapeutic strategy in breast cancer patients with resected primary tumors.

Keywords:
Small-sized polymeric micelles; Docetaxel; Metastasis; 4T1 Mammary carcinoma; Malignant breast cancer; Primary tumor resected