title: Facile preparation of paclitaxel loaded silk fibroin nanoparticles for enhanced antitumor efficacy by locoregional drug delivery.
abstract: Non-toxic, safe materials and preparation methods are among the most important factors when designing nanoparticles (NPs) for future clinical application. Here we report a novel and facile method encapsulating anticancer drug paclitaxel (PTX) into silk fibroin (SF), a biocompatible and biodegradable natural polymer, without adding any toxic organic solvents, surfactants or other toxic agents. The paclitaxel loaded silk fibroin nanoparticles (PTX-SF-NPs) with a diameter of 130 nm were formed in an aqueous solution at room temperature by self-assembling of SF protein, which demonstrated mainly silk I conformation in the NPs. In cellular uptake experiments, coumarin-6 loaded SF NPs were taken up efficiently by two human gastric cancer cell lines BGC-823 and SGC-7901. In vitro cytotoxicity studies demonstrated that PTX kept its pharmacological activity when incorporating into PTX-SF-NPs, while SF showed no cytotoxicity to cells. The in vivo antitumor effects of PTX-SF-NPs were evaluated on gastric cancer nude mice exnograft model. We found that locoregional delivery of PTX-SF-NPs demonstrated superior antitumor efficacy by delaying tumor growth and reducing tumor weights compared with systemic administration. Furthermore, the organs of mice in NP treated groups didn't show obvious toxicity, indicating the in vivo safety of SF NPs. These results suggest that SF NPs are promising drug delivery carriers, and locoregional delivery of SF NPs could be a potential future clinical cancer treatment regimen.
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University , Clinical Cancer Institute of Nanjing University , 321 Zhongshan Road, Nanjing 210008, China.
authors.forename: Puyuan
authors.initials: P
authors.lastname: Wu
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Rutian
authors.initials: R
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Zhen
authors.forename: Guofeng
authors.initials: G
authors.lastname: Yue
authors.forename: Huiyu
authors.initials: H
authors.lastname: Wang
authors.forename: Fangbo
authors.initials: F
authors.lastname: Cui
authors.forename: Fenglei
authors.initials: F
authors.lastname: Wu
authors.forename: Mi
authors.initials: M
authors.lastname: Yang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Qian
authors.forename: Lixia
authors.initials: L
authors.lastname: Yu
authors.forename: Xiqun
authors.initials: X
authors.lastname: Jiang
authors.forename: Baorui
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005349:Fibroins / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage*; D047011:Silk; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D047011:Silk; D005349:Fibroins; D017239:Paclitaxel