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J Biomater Appl. 2019 Apr 10:885328219839254. doi: 10.1177/0885328219839254. [Epub ahead of print]

Simultaneous delivery of gene and chemotherapeutics via copolymeric micellar nanoparticles to overcome multiple drug resistance to promote synergistic tumor suppression.

Author information

1
1 Department of Urology, Affiliated Hospital of Huzhou Teacher's College, The First People's Hospital of Hu Zhou, Hu Zhou, China.
2
2 Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
3
3 State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Changchun, China.
4
4 School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, China.
5
5 School of Ophthalmology & Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, China.
6
6 Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Science, Wenzhou, China.

Abstract

Combination of chemotherapy and small interfering RNA (siRNA)-based nanotherapeutics could cooperatively and effectively suppress multiple drug resistance in cancer development. Particularly, nano-delivery systems that efficiently encapsulate two or more therapeutic payloads to the tumor-targeted sites have been proven significantly. Here, we prepared a micellar nanoparticle formed by monomethoxy poly (ethylene glycol)-block-poly(ε-caprolactone)-block-poly(L-lysine)/cholesterol (mPEG-b-PCL-b-PLL/Chol, further abbr. as "P"). In this work, PCL as the hydrophobic core to encase doxorubicin and PLL as the cationic moiety to bind with negatively charged siRNA are used to achieve the co-delivery of therapies in one platform. The results showed that the micellar nanoparticle is capable of delivering siRNA and doxorubicin simultaneously to the same tumor cells, and consequently displays enhanced inhibition efficiency on MCF-7/ADR cells. Moreover, real-time polymerase chain reaction (RT-PCR) and Western blot experiments indicated that the co-delivery of micelleplex-delivering B-cell lymphoma 2 specific siRNA (siBcl) successfully down-regulated the expression of Bcl-2 protein, which triggers chemotherapy to be more sensitive to the cancer cells. Therefore, the strategy of co-delivering anticancer drug and siRNA showed promising potential in reversing drug resistance of tumor cells.

KEYWORDS:

Micellar nanoparticle; co-delivery; multiple drug resistance; siRNA; synergistic effect

PMID:
30971178
DOI:
10.1177/0885328219839254

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