title: A Collaborative Assembly Strategy for Tumor-Targeted siRNA Delivery.
abstract: A novel "collaborative assembly" approach was reported for the synthesis of an siRNA delivery system via a combination of an electrostatically driven physical assembly and a facile click reaction-mediated chemical assembly, which showed various advantages of more safety, efficiency, and flexibility over the conventional approach that is only based on the physical assembly. This strategy remained a high cationic property of lipid-based complex for high siRNA loading capacity. The direct chemical modification of a model polyanion, hyaluronic acid (HA) on the cationic complex via click chemistry shielded the positive charge of complex without affecting the siRNA binding, which reduced the toxicity and enhanced the blood stability of the complex. In addition, the incorporated polyanion might be prefunctionalized, which endued the carrier with better biological characteristics such as long circulating or tumor targeting. We demonstrated that the obtained lipid-polymer hybrid nanoparticle (RSC-HA) using collaborative assembly presented greater in vivo stability in the blood for efficient tumor targeting than the physically assembled RSC/HA in which HA was physically adsorbed on the complex. After endocytosis into the cells, the protection of RSC-HA on siRNA turned off, while the release of siRNA induced by the intracellular signals for enhanced gene-silencing capacity. This combination of physical and chemical assemblies provides an efficient strategy for the exploitation of safe, stable, and functionalized siRNA delivery systems.
authors: State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
authors: Qiong
authors: Q
authors: Sun
authors: State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
authors: Zisheng
authors: Z
authors: Kang
authors: State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
authors: Lingjing
authors: L
authors: Xue
authors: State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
authors: Yunkai
authors: Y
authors: Shang
authors: State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
authors: Zhigui
authors: Z
authors: Su
authors: State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
authors: Hongbin
authors: H
authors: Sun
authors: State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
authors: Qineng
authors: Q
authors: Ping
authors: State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
authors: Ran
authors: R
authors: Mo
authors: State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
authors: Can
authors: C
authors: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D020868:Gene Silencing / Q000187:drug effects; D018014:Gene Transfer Techniques; D006801:Humans; D008055:Lipids / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011108:Polymers / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats
chemical_list: D008055:Lipids; D011108:Polymers; D034741:RNA, Small Interfering