摘要
目的探索叶酸偶联壳聚糖(FA-CTS)纳米粒的合成方法及对肿瘤细胞的靶向性。方法利用叶酸活性酯与壳聚糖分子上的氨基反应形成稳定的酰胺键,制备FA-CTS。再利用壳聚糖在偏酸性溶液中带正电荷,在高速磁力搅拌作用下能与阴离子凝集的特性,将紫杉醇(PTX)做模型药物,制备负载PTX叶酸偶联壳聚糖(FA-CTS/PTX)纳米粒。采用荧光标记法和MTT法评价其肿瘤细胞靶向性。结果所制备的FA-CTS/PTX纳米粒,形态均质规则,无粘连,平均粒径282.8nm,包封率75.4%,载药量9.0%。荧光标记法结果表明FA-CTS纳米粒的肿瘤细胞亲和性均高于普通CTS纳米粒。MTT法结果显示FA-CTS/PTX纳米粒组的肿瘤细胞抑制率均高于普通CTS/PTX纳米粒组。结论合成的FA-CTS纳米粒可通过叶酸受体途径特异靶向于叶酸受体丰富的肿瘤细胞。
Objective To synthesize and characterize paclitaxel （PTX）-loaded folate-conjugated chitosan （FA-CTS/PTX） nanoparticles and evaluate its cytotoxicity in vitro. Methods CTS/PTX and FA-CTS/PTX nanoparticles were prepared using reductive amidation and ionic gelation ofchitosan with tripolyphosphate anions （TPP）. The particle size was determined by laser scattering and the morphology observed using transmission electron microscopy, and the PTX content in the nanoparticles was determined using ultraviolet spectrophotometer at 227 nm. The in vitro cytotoxicity of the nanoparticles against HeLa cells was evaluated by MTT assay. Fluorescence microscopy was used to observe the HeLa cells incubated with FA-chitosan nanoparticles in the presence or absence of folic acid in the culture medium. Results PTX loading did not cause adhesion of the FA-CTS nanoparticles, which presented with uniform spherical morphology with an average diameter of 282.8 nm. The loading and encapsulation efficiencies of FA-CTS/PTX were 9.0% and 75.4%, respectively. The FA-CTS nanoparticles showed a greater extent ofintracellular uptake in the absence of folic acid, indicating that the cellular uptake of the nanoparticles occurred through endocytosis mediated by the folate receptors. The PTX-loaded FA-CTS nanoparticles exhibited potent cytotoxicity against HeLa cells, an effect 2- to 3-fold stronger than that of PTX-loaded CTS nanoparticles. Conclusion FA-CTS can be a promising drug carrier with high efficiency in condensing drug, good tumor-targeting ability and low cytotoxicity.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2008年第12期2183-2186,共4页
Journal of Southern Medical University
关键词
叶酸偶联壳聚糖纳米粒
紫杉醇
纳米粒
药物载体
folate-conjugated chitosan nanoparticles
paclitaxel
nanoparticles
drug carrier
