title: Enhanced antitumor efficacy of folate modified amphiphilic nanoparticles through co-delivery of chemotherapeutic drugs and genes.
abstract: Folate (FA) modified amphiphilic linoleic acid (LA) and poly (β-malic acid) (PMLA) double grafted chitosan (LMC) nanoparticles (NPs) with optimum grafting degrees of hydrophobic LA and hydrophilic PMLA were developed for the co-delivery of paclitaxel (PTX) and survivin shRNA-expressing plasmid (iSur-pDNA). The resultant NPs exhibited particle size of 161 nm and zeta potential of 43 mV. FA modification and the increasing grafting degrees of LA and PMLA were correlated with the suppressed protein adsorption, the inhibited release of PTX, and the accelerated dissociation of pDNA. PTX loading, cellular uptake, nuclear accumulation of pDNA, in vitro gene silencing efficiency, and cell growth inhibition were promoted by FA modification and higher grafting degree of LA, but impeded by increasing grafting degree of PMLA. In tumor-bearing mice, co-delivery of PTX and iSur-pDNA exhibited enhanced antitumor efficacy and prolonged survival period as compared with single delivery of PTX or iSur-pDNA. These results indicated that amphiphilic LMC NPs could serve as a promising platform for the co-delivery of antitumor drugs and genes, and highlighted the importance of adjusting the hydrophobic and hydrophilic grafting degrees.
authors.affiliation: State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Bojie
authors.initials: B
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, Shanghai 200433, China. Electronic address: chyin@fudan.edu.cn.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yin
mesh_terms: D000327:Adsorption; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D003850:Deoxyribonuclease I / Q000378:metabolism; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D019787:Linoleic Acid / Q000737:chemistry; D008293:Malates / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000494:pharmacology*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D055672:Static Electricity; D013501:Surface-Active Agents / Q000737:chemistry*; D000077022:Survivin
chemical_list: D000970:Antineoplastic Agents; C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D008293:Malates; D011108:Polymers; D012333:RNA, Messenger; D012097:Repressor Proteins; D013501:Surface-Active Agents; D000077022:Survivin; C121060:poly(malic acid); D012710:Serum Albumin, Bovine; D048271:Chitosan; D005492:Folic Acid; D019787:Linoleic Acid; D003850:Deoxyribonuclease I; D017239:Paclitaxel
keywords: Amphiphilic nanoparticles; Antitumor efficacy; Co-delivery; FA modification; Hydrophilic modification; Hydrophobic modification