title: Paclitaxel-loaded trimethyl chitosan-based polymeric nanoparticle for the effective treatment of gastroenteric tumors.
abstract: Gastroenteric cancer is one of the most prevalent cancers and is responsible for most cancer-related deaths worldwide. Paclitaxel (PTX), a classical microtubule inhibitor, is indicated in the treatment of gastric/gastroenteric cancers. In the present study, trimethyl chitosan (TMC)-loaded PTX (TMC-PTX) was prepared and evaluated for its therapeutic effect in gastric cancers. A spherical shaped nanosized TMC-PTX particle was formed with high loading capacity (~30%) for PTX. The nanoparticles (NPs) showed a sustained release pattern (~70%) for up to 96 h of study period. The positively charged NPs were preferentially internalized by Caco-2 cells. TMC-PTX inhibited the gastric cell proliferation with an IC50 value of 0.6 µg in NCI-N87 cells while it was 1.26 µg in the SGC-7901 cell line after 24 h exposure. The apoptosis assay (Annexin V/PI) showed a large presence of cells in the early and late apoptosis chamber, while cell cycle analysis showed a marked G2/M phase arrest (50-60%) in NCI-N87 and SGC-7901 cell lines indicating its potent anti-proliferative effect. The in vivo antitumor study in NCI-N87 and SGC-7901 bearing xenograft model showed a superior chemotherapeutic efficacy for TMC-PTX NP. The NP group significantly reduced the tumor growth with no obvious sign of systemic side-effects (safety). Collectively, our results suggest that the microtubule inhibitory effect of PTX-loaded polymer NP could be a promising system for the treatment of gastroenteric cancers.
authors: Department of Gastroenterology, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi 330029, P.R. China.
authors: Rong-Feng
authors: RF
authors: Song
authors: Department of Hepatic Neoplasms Surgery, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi 330029, P.R. China.
authors: Xiao-Jun
authors: XJ
authors: Li
authors: Department of Thoracic Surgery, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi 330029, P.R. China.
authors: Xiao-Liang
authors: XL
authors: Cheng
authors: Department of Pathology, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi 330029, P.R. China.
authors: Ai-Rong
authors: AR
authors: Fu
authors: Department of Gastroenterology, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi 330029, P.R. China.
authors: Yan-Hua
authors: YH
authors: Wang
authors: Department of Gastroenterology, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi 330029, P.R. China.
authors: Yan-Jun
authors: YJ
authors: Feng
authors: Department of Gastroenterology, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi 330029, P.R. China.
authors: Yan
authors: Y
authors: Xiong
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan; D016503:Drug Delivery Systems; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy; D006801:Humans; D007421:Intestine, Small; D051379:Mice; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D011108:Polymers; D013274:Stomach Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C118071:N-trimethyl chitosan chloride; D011108:Polymers; D048271:Chitosan; D017239:Paclitaxel