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Synthesis of cleavable multi-functional mikto-arm star polymer by RAFT polymerization: example of an anti-cancer drug 7-ethyl-10-hydroxycamptothecin (SN-38) as functional moiety

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Abstract

Multi-functional mikto-arm star polymers containing three different arms [hydrophilic, SN-38-P(OEGMA8–9)11, cationizable, SN-38-P(DMAEMA)38 and hydrophobic, SN-38-P(BMA)26] were prepared by RAFT polymerization via an arm-first approach using a cleavable cross-linker. The star polymers were cleaved to the linear arms with tributylphosphine as a reducing agent. The decrease in molecular weight observed is consistent with the initial stars having approximately five arms. Blue fluorescence was observed when a solution of mikto-arm star was irradiated under a 365 nm light proving the retention of the SN-38 moiety during star formation by RAFT polymerization. Thus these polymer-drug conjugates can be considered as potential delivery vehicles for cancer therapy. The P(DMAEMA) arms can be quaternized using iodomethane, allowing star polymers to bind negatively charged small interfering RNA (siRNA) and potentially be used as a carrier for that material.

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Authors and Affiliations

  1. College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China

    XiaoHu Wei & WanTai Yang

  2. Materials Science and Engineering, The Commonwealth Scientific and Industrial Research Organisation(CSIRO), Bag 10, Clayton South, VIC, 3169, Australia

    XiaoHu Wei, Pathiraja A. Gunatillake, Graeme Moad, Ezio Rizzardo, Julien Rosselgong & San H. Thang

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  1. XiaoHu Wei
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  2. Pathiraja A. Gunatillake
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  3. Graeme Moad
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  4. Ezio Rizzardo
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  5. Julien Rosselgong
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  6. WanTai Yang
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  7. San H. Thang
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Correspondence to WanTai Yang or San H. Thang.

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Wei, X., Gunatillake, P.A., Moad, G. et al. Synthesis of cleavable multi-functional mikto-arm star polymer by RAFT polymerization: example of an anti-cancer drug 7-ethyl-10-hydroxycamptothecin (SN-38) as functional moiety. Sci. China Chem. 57, 995–1001 (2014). https://doi.org/10.1007/s11426-014-5128-5

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