Pluronic P123 modified nano micelles loaded with doxorubicin enhanced tumor-suppressing effect on drug-resistant breast cancer cells.

Xiaoyu Zhang,Lijun Jin,Jie Bai,Weibin Chen,Hui Zhang,Zunyi Wang,Xiaoning Kang

doi:10.18632/aging.103138

Xiaoyu Zhang, Lijun Jin + Show 5 more

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https://doi.org/10.18632/aging.103138

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Abstract

Objective: Nano micelles (NMs) have been widely used for various biomedical applications due to its unique physiochemical properties. This study aimed to investigated the anti-tumor effect of doxorubicin (Dox)-loaded Pluronic P123 (P123) and PEG2000-DSPE mixed NMs in drug-resistant breast cancer cells.Results: The expression of P-gp and MDR1 gene was highly expressed in MCF-7R but not MCF-7 cells. The cellular uptake of P123-PEG2000-DSPE (Dox) was higher than that of free Dox and PEG2000-DSPE (Dox) in MCF-7R cells. Furthermore, compared with free Dox, both PEG2000-DSPE (Dox) and P123-PEG2000-DSPE (Dox) significantly diminished cell viability, and promoted cell apoptosis in MCF-7R cells. In addition, the P123-modified NMs obviously inhibited the expression of P-gp and MDR1.Conclusions: P123-PEG2000-DSPE (Dox) had a superior anti-tumor activity than PEG2000-DSPE (Dox) in MCF-7R cells through P-gp-mediated drug excretion and drug resistance mechanisms.Methods: The PEG2000-DSPE NMs (PEG2000-DSPE), P123 and PEG2000-DSPE mixed NMs (P123-PEG2000-DSPE), Dox-loaded PEG2000-DSPE NMs (PEG2000-DSPE (Dox)), and Dox-loaded Pluronic P123 and PEG2000-DSPE mixed NMs (P123-PEG2000-DSPE (Dox)) were prepared, and then the morphologies and the size distribution of PEG2000-DSPE (Dox) and P123-PEG2000-DSPE (Dox) were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively.

Highlights

As the common malignant tumors, breast cancer (BC) usually originates from the mammary epithelial tissues, with high rates of morbidity and mortality [1, 2]
Another in vitro study has shown that quercetin loaded Nano micelles (NMs) significantly inhibit cell proliferation and induce apoptosis compared with free quercetin in PC-3 cells [29]
Consistent with previous studies, our study www.aging-us.com revealed that compared with free Dox, both PEG2000DSPE (Dox) and P123-PEG2000-DSPE (Dox) significantly diminished cell proliferation and induced cell apoptosis in MCF-7R cells

Summary

Introduction

As the common malignant tumors, breast cancer (BC) usually originates from the mammary epithelial tissues, with high rates of morbidity and mortality [1, 2]. One of the major obstacles for cancer treatment is drug resistance to chemotherapeutic drugs, which should be responsible for the failed chemotherapy [7]. P-gp, an ATP-binding cassette transporter, is thoroughly studied www.aging-us.com as the key mechanism of multi-drug resistance (MDR) in cancers [10, 11]. It has been reported that P-gp encoded by MDR1 gene plays pivotal role in the efflux mechanism, which can pump to extrude various kinds of drugs out of MDR cancer cells acting as a drug efflux [10, 11]. Inhibiting P-gp expression is considered as a possible strategy for the resensitization of MDR cancer cells through mediating drugs efflux, thereby improving the success rate of chemotherapy in patients with MDR tumor [12,13,14]

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