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

Jianguo Gao, Lingxiao Chen, Ruogu Qi, Zhihua Zhou, Zaian Deng, Jue Shi, Tao Qin, Shengzhe Zhao, Yuna Qian, Jianliang Shen
Journal of Biomaterials Applications 2019 April 10, : 885328219839254
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.

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