title: Cationic Polyphosphazene Vesicles for Cancer Immunotherapy by Efficient in Vivo Cytokine IL-12 Plasmid Delivery.
abstract: 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.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University , 866 Yu-Hang-Tang Road, Hangzhou 310058, China.
authors.forename: Menghua
authors.initials: M
authors.lastname: Gao
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University , 866 Yu-Hang-Tang Road, Hangzhou 310058, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhu
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University , 866 Yu-Hang-Tang Road, Hangzhou 310058, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wu
authors.affiliation: Ministry of Education (MOE) Key Laboratory of Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , 38 Zheda Road, Hangzhou 310027, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Qiu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007167:Immunotherapy; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000737:chemistry; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010957:Plasmids / Q000008:administration & dosage*; D011108:Polymers / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D009943:Organophosphorus Compounds; D011108:Polymers; C108974:poly(phosphazene); D018664:Interleukin-12