Cationic Polyphosphazene Vesicles for Cancer Immunotherapy by Efficient in Vivo Cytokine IL-12 Plasmid Delivery

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• 作者：Menghua Gao ; Xiumei Zhu ; Liping Wu ; Liyan Qiu
• 刊名：Biomacromolecules
• 出版年：2016
• 出版时间：June 13, 2016
• 年：2016
• 卷：17
• 期：6
• 页码：2199-2209
• 全文大小：712K
• 年卷期：0
• ISSN：1526-4602

文摘

To circumvent the severe toxicity of the systemic delivery of IL-12 protein and the limits of local administration of IL-12 gene, we constructed a polymersome system for systemic delivery of recombinant murine IL-12 plasmid (pmIL-12) based on amphiphilic polyphosphazenes containing weakly cationic N,N-diisopropylethylenediamine (DPA) as hydrophobic groups and monomethoxy poly(ethylene glycol) (mPEG) as hydrophilic tails. By simple dialysis method, pmIL-12 was successfully loaded into polymersomes due to the combination effect of physical encapsulation and electrostatic interaction. This pmIL-12 polymersome delivery system was validated with good biocompatibility and stability despite of serum protein and DNase challenging. The results of in vivo antitumor experiments showed that intravenous injection of pmIL-12 polymersomes achieved significant suppression of tumor growth in BALB/c mice bearing CT-26 colon carcinoma. The analysis revealed that the mechanism was related to the antitumor immune response induced by efficient transfection of pmIL-12 polymersomes, which maybe involved lymphocytes infiltration and angiogenic inhibition at the tumor site.