title: A novel local anti-colorectal cancer drug delivery system: negative lipidoid nanoparticles with a passive target via a size-dependent pattern.
abstract: The nontoxic, targeted and effective delivery of nucleic acid drugs remains an important challenge for clinical development. Here, we describe a novel negative lipidoid nanoparticle delivery system, providing entrapment-based transfection agents for local delivery of siRNA to the colorectal cancer focus. The delivery system was synthesized with lipidoid material 98N12-5(1), mPEG2000-C12/C14 glyceride and cholesterol at a desired molar ratio to realize the anionic surface charge of particles, which could alleviate to a larger degree the inflammatory response and immune stimulation of the organism, embodying dramatic biocompatibility. In particular, mPEG2000-C12/C14 glyceride was selected to ameliorate the stability of the delivery system and protection of nucleic acids by extending the tail length of the carbons, crucial also to neutralize the positive charge of 98N12-5(1) to form a resultant anionic particle. In vivo experiments revealed that a particle size of 90 nm perfectly realized a passive target in a size-dependent manner and did not affect the function of the liver and kidneys by a local delivery method, enema. We clarified that the uptake of negative lipidoid nanoparticles internalized through a lipid raft endocytotic pathway with low cytotoxicity, strong biocompatibility and high efficacy. This study suggests that negative lipidoid nanoparticles with enema delivery constitute, uniquely and appropriately, a local anti-colorectal cancer nucleic acid drug delivery platform, and the application of similar modes may be feasible in other therapeutic settings.
authors: Medical Laboratory Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, People's Republic of China.
authors: Weifeng
authors: W
authors: Ding
authors: Feng
authors: F
authors: Wang
authors: Jianfeng
authors: J
authors: Zhang
authors: Yibing
authors: Y
authors: Guo
authors: Shaoqing
authors: S
authors: Ju
authors: Huimin
authors: H
authors: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016503:Drug Delivery Systems; D004705:Endocytosis; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D007422:Intestines / Q000473:pathology; D007668:Kidney / Q000503:physiopathology; D008055:Lipids / Q000737:chemistry*; D008099:Liver / Q000503:physiopathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D034741:RNA, Small Interfering; C491959:Tnfsf13 protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13