摘要
通过脱苄基和酯化反应,在聚(γ-苄基L-谷氨酸酯)-b-聚乙二醇(PBLG-b-PEG)嵌段共聚物的PBLG嵌段侧基修饰上可光交联的肉桂酰氧基,得到聚(γ-苄基L-谷氨酸酯-co-肉桂基L-谷氨酸酯)-b-聚乙二醇(P(BLG/CLG)-b-PEG)嵌段共聚物。将P(BLG/CLG)-b-PEG分别与PBLG均聚物、聚苯乙烯(PS)均聚物共混自组装,制备出具有核-壳结构的棒状和球状仿病毒粒子(VLPs),其中,均聚物形成棒状或球状内核,嵌段共聚物构成外壳。利用紫外光照射交联CLG链段固定VLPs壳结构,以N,N′-二甲基甲酰胺(DMF)溶解去除均聚物内核,制备中空仿病毒粒子(HVLPs)。采用扫描电镜、透射电镜表征了组装体的微观形貌。研究表明:DMF可以溶解去除球状VLPs的PS均聚物内核,制备出表面具有条纹的球状HVLPs;而棒状VLPs的PBLG均聚物内核不能被DMF溶解去除。以阿霉素(DOX)为模型药物,研究了球状HVLPs的载药性能,其对DOX的相对载药量可以达到230%,在pH=7.4时72 h药物累计释放量达到80%。
Virus-like particles(VLPs)have attracted increasing attentions in the field of drug-delivery.The ordered surface nanostructure is one of the essential structures of the natural virus.The preparation and drug-loading property of polypeptidebased hollow VLPs with ordered surface nanostructures were investigated.Starting from poly(γ-benzyl-L-glutamate)-blockpoly(ethylene glycol)(PBLG-b-PEG)block copolymers,through deprotection of the benzyl group and subsequent esterification reaction,poly(γ-benzyl-L-glutamate-co-γ-cinnamyl-L-glutamate)-block-poly(ethylene glycol)(P(BLG/CLG)-bPEG)block copolymers were synthesized,in which the cinnamyl group was photo-cross-linkable.The photo-cross-linking process of the P(BLG/CLG)-b-PEG block copolymers was tracked by the UV-Vis spectrum.Adding water to the solution of P(BLG/CLG)-b-PEG block copolymer and PS homopolymers in THF-DMF mixture(volume ratio 1/1),spherical VLPs were self-assembled from the polymer mixtures.These VLPs contained a PS homopolymer core and P(BLG/CLG)-b-PEG block copolymer shell,and the P(BLG/CLG)-b-PEG block copolymers packed orderly forming strips on the surface.When replacing the PS homopolymers by rigid PBLG homopolymers,rod-like VLPs were obtained in which the PBLG homopolymers formed bundles and P(BLG/CLG)-b-PEG block copolymers self-assembled on the surface of the PBLG homopolymer bundles into helical nanostructures.Under UV-irradiation atλ=254 nm,the P(BLG/CLG)blocks in the shell of both the spherical and the rod-like VLPs were cross-linked through the photodimerization of the cinnamyloxy groups.To the solution of the shell-crosslinked spherical VLPs,adding a large amount of DMF could remove the PS core-forming hollow virus-like particles(HVLPs),and the strip patterns on the surface were retained.However,for the rod-like VLPs,under similar conditions,the PBLG homopolymers in the core could not be removed.The drug-loading capacity of the spherical HVLPs was evaluated by using doxorubicin(DOX)as a model drug.It was found that DOX was successfully loaded into the HVLPs with a high relative drug-loading mass fraction(230%).Releasing studies revealed that the drugs could gradually release from the VLPs,and 72 h accumulate releasing mass fraction reached about 80%.This work provides a method to prepare polypeptide-based HVLPs with surface nanostructures,and these HVLPs could find applications for drug delivery.
作者
王红权
续文恒
张朔
姜翔宇
李慧
陈家琛
蔡春华
林嘉平
WANG Hongquan;XU Wenheng;ZHANG Shuo;JIANG Xiangyu;LI Hui;CHEN Jiachen;CAI Chunhua;LIN Jiaping(Shanghai Key Laboratory of Advanced Polymeric Materials,School of Materials Science and Engineering,East China University of Science and Technology,Shanghai 200237,China)
出处
《功能高分子学报》
CAS
CSCD
北大核心
2020年第3期245-252,共8页
Journal of Functional Polymers
基金
国家自然科学基金(51573049)。
关键词
聚肽
自组装
仿病毒组装体
中空纳米粒子
药物载体
polypeptide
self-assembly
virus-like particles
hollow nanoparticles
drug carriers
