title: Serum-resistant complex nanoparticles functionalized with imidazole-rich polypeptide for gene delivery to pulmonary metastatic melanoma.
abstract: To enhance serum-resistance and overcome the lysosomal barrier are effective and feasible strategies to increase the transfection efficiency of non-viral gene delivery system. For the systemic delivery of therapeutic gene, we previously developed self-assemble carboxymethyl poly(l-histidine) (CM-PLH)/poly(β-amino ester) (PbAE)/pDNA ternary complex nanoparticles based on electrostatic coating as an effective pDNA carrier. Recharging cationic PbAE/pDNA polyplexes with CM-PLH was a promising method to reduce the cytotoxicity and enhance the stability in vivo of positive charged polyplexes. In the present study, the transfection activities of ternary complex nanoparticles were further evaluated in vitro and in vivo. The transfection efficiency of ternary complex nanoparticles showed significant serum-resistance (CM-PLH-containing (51.9±4.35)% in 50% FBS>CM-PLH-free (14.7±5.66)% in 50% FBS), cell line dependent (HEK293>MCF-7>COS7>B16F10>A549>Hela>SPC-A1>CHO>SKOV3) and incubation period dependent (24 h, 20 h, 16 h>12 h>8 h>4 h>2 h>1 h>0.5 h). After transfected with ternary complex nanoparticles loading pGV240-MDA-7/IL-24, the B16F10 cells exhibited significant apoptosis and proliferation inhibition due to the expression of IL-24. Moreover, in the pulmonary metastatic melanoma model, ternary complex nanoparticles loading pGV240-MDA-7/IL-24 showed significant antitumor therapeutic efficacy in vivo. These results suggested that CM-PLH/PbAE/pDNA ternary complex nanoparticles were promising and challenging gene vector for practical application.
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China; Laboratory for Drug Delivery and Biomaterials, Faculty of Pharmacy, University of Manitoba, 750 McDermot Avenue, Winnipeg, Manitoba R3E 0T5, Canada.
authors.forename: Jijin
authors.initials: J
authors.lastname: Gu
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, 818 Tianyuan Road, Nanjing 210029, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Xin
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Fang
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China. Electronic address: shaxy@fudan.edu.cn.
authors.forename: Xianyi
authors.initials: X
authors.lastname: Sha
mesh_terms: D000818:Animals; D002412:Cations; D002460:Cell Line; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D007378:Interleukins / Q000235:genetics; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D008546:Melanoma, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D010455:Peptides / Q000737:chemistry; D010957:Plasmids; D011108:Polymers / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D044967:Serum / Q000378:metabolism; D014162:Transfection; D000099180:Interleukin-24
chemical_list: D002412:Cations; D004247:DNA; D007093:Imidazoles; D007378:Interleukins; D010455:Peptides; D011108:Polymers; D011506:Proteins; D000099180:Interleukin-24; C533250:carboxymethyl polyhistidine; C507253:poly(beta-amino ester); C029899:imidazole
keywords: Carboxymethyl poly(l-histidine); Complex nanoparticles; Gene delivery; MDA-7/IL-24; Poly(β-amino ester)