2011.01.28, Professor Wang Jun Published a paper in Biomaterials

  • 2011.01.28, Professor Wang Jun published a paper entitled “A biodegradable amphiphilic and cationic triblock copolymer for the delivery of siRNA targeting the acid ceramidase gene for cancer therapy” in Biomaterials
    Author:Cheng-Qiong Mao, Jin-Zhi Du, Tian-Meng Sun, Yan-Dan Yao, Pei-Zhuo Zhang, Er-Wei Song, and Jun Wang
    Abstract:
    One of the key challenges in the development of RNA interference-based cancer therapy is the lack of an efficient delivery system for synthetic small interfering RNAs (siRNAs) that would enable efficient uptake by tumor cells and allow for significant knockdown of a target transcriptin vivo. Here, we describe a micelleplex system based on an amphiphilic and cationic triblock copolymer, which can systemically deliver siRNA targeting the acid ceramidase (AC) gene for cancer therapy. This triblock copolymer, consisting of monomethoxy poly(ethylene glycol), poly(ε-caprolactone) and poly(2-aminoethyl ethylene phosphate), self-assembles into micellar nanoparticles (MNPs) in aqueous solution with an average diameter of 60 nm and a zeta potential of approximately 48 mV. The resulting micelleplex, formed by the interaction of MNPs and siRNA, was effectively internalized by BT474 breast cancer cells and siRNA was subsequently released, resulting in significant gene knockdown. This effect was demonstrated by significant down-regulation of luciferase expression in BT474-luciferase cells which stably express luciferase, and suppression of AC expression in BT474 cells at both the transcriptional and protein level, following delivery of specific siRNAs by the micelleplex. Furthermore, a micelleplex carrying siRNA targeting the AC (micelleplexsiAC) gene was found to induce remarkable apoptosis and reduce the proliferation of cancer cells. Systemic delivery of micelleplexsiACsignificantly inhibited tumor growth in a BT474 xenograft murine model, with depressed expression of AC and no positive activation of the innate immune response, suggesting therapeutic promise for micelleplex siRNA delivery in cancer therapy. (doi:10.1016/j.biomaterials.2011.01.006)
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