title: Codelivery of mTERT siRNA and paclitaxel by chitosan-based nanoparticles promoted synergistic tumor suppression.
abstract: Clinical applications of siRNA are being hindered by poor intracellular uptake and enzymatic degradation. To address these problems, we devised an oral delivery system for telomerase reverse transcriptase siRNA using N-((2-hydroxy-3-trimethylammonium) propyl) chitosan chloride (HTCC) nanoparticles (HNP). Both the porous structure and the positive charge of HNP facilitated siRNA encapsulation. The outer coating of HTCC not only protected siRNA from enzymatic degradation, but also improved siRNA permeability in intestine tract. In vivo and in vitro experiments proved that HNP could effectively deliver siRNA to lesion site and further into tumor cells. On the basis of confirming the antitumor activity of HNP:siRNA, we continued to encapsulate a hydrophobic chemotherapeutic drug-paclitaxel (PTX) into HNP to form a "two-in-one" nano-complex (HNP:siRNA/PTX). We demonstrated that HNP:siRNA/PTX could simultaneously ferry siRNA and PTX into tumor cells and increase drug concentration, which, in particular, was much more effective in tumor suppression than that of traditional cocktail therapy. These results suggested that the HNP, as a powerful delivery system for both siRNA and chemotherapeutic drug, would have a far-reaching application in human cancer therapy.
authors: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China.
authors: Wei
authors: W
authors: Wei
authors: Pi-Ping
authors: PP
authors: Lv
authors: Xiao-Ming
authors: XM
authors: Chen
authors: Zhan-Guo
authors: ZG
authors: Yue
authors: Qiang
authors: Q
authors: Fu
authors: Shi-Ying
authors: SY
authors: Liu
authors: Hua
authors: H
authors: Yue
authors: Guang-Hui
authors: GH
authors: Ma
mesh_terms: D000042:Absorption / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018938:Caco-2 Cells; D002232:Carbocyanines; D018827:Carcinoma, Lewis Lung; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D020868:Gene Silencing / Q000187:drug effects; D018014:Gene Transfer Techniques; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010539:Permeability / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D002232:Carbocyanines; C550160:N-(2-hydroxypropyl)-3-trimethylammonium chitosan; D000644:Quaternary Ammonium Compounds; D034741:RNA, Small Interfering; C085321:cyanine dye 5; D048271:Chitosan; D019098:Telomerase; C509187:Tert protein, mouse; D017239:Paclitaxel