期刊
JOURNAL OF MATERIALS CHEMISTRY B
卷 2, 期 35, 页码 5910-5924出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4tb00814f
关键词
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资金
- National Natural Science Foundation of China [21304099, 51203162, 51103159, 51373177]
- National High Technology Research and Development Program [2014AA020708, 2012AA022703, 2012AA020804]
- Instrument Developing Project of the Chinese Academy of Sciences [YZ201253, YZ201313]
- Open Funding Project of the National Key Laboratory of Biochemical Engineering [Y22504A169]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA09030301-3]
Co-delivery of siRNAs and chemotherapeutic drugs to kill tumors have achieved superior tumor growth inhibition. However, due to siRNAs and chemotherapeutic drugs with different molecular properties, co-delivery carriers use more cationic materials to bind siRNAs and excessive inert materials to embed drugs, causing low drug-loading contents and systemic toxicity. To achieve this goal, doxorubicin (DOX) is chemically conjugated to stearoyl chloride (C18) through N-methyldiethanol amine (N) as cross-linker to form amphiphilic C18-N-DOX. C18-N-DOX contains a tertiary amine that can complex siRNAs at low pH (pH 3) and reduce the density of the positive charges on the surface of NPs at physiological pH (pH 7.4). C18-N-DOX, together with 1,2-distearoyl-sn-g/ycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000) DSPE-PEG2000, self-assemble into DOX-prodrug nanoparticles (DOX-prodrug NPs), which bind siRNAs in citrate buffer (pH 3) to form DOX-prodrug NPs/siRNA. After replacing citrate buffer (pH 3) with PBS (pH 7.4), DOX-prodrug NPs/siRNA have slight negative charges due to complexed more siRNAs. In this study, clear evidence is shown that DOX-prodrug NPs can deliver siRNA to the same tumor cells both in vitro and in vivo. Moreover, DOX-prodrug NPs/siRNA show a great effect on inhibiting tumor cell growth both in vitro and in vivo. Therefore, the DOX-prodrug NPs are promising candidates as siRNAs delivery system for tumor therapy.
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