光响应聚倍半硅氧烷纳米载体及其光控药物释放性能

Light controlled release system based on photoresponsive bridged polysilsesquioxane nanocarriers

设计并合成了氨基甲酸-N,N-双[3-(三甲氧基硅基)丙基]-(2-硝基苯基)甲酯(BS)光响应性桥联硅烷单体,采用1H NMR、13C NMR、29Si NMR和质谱对其进行了表征,硅烷的邻硝基苄基桥联结构单元具有光响应性能,在254 nm光照射下会发生光致断裂.通过溶胶-凝胶过程,利用BS桥联硅烷制备了具有光响应性能的聚倍半硅氧烷纳米粒子(BPS),其平均直径为127 nm,粒径分布窄(PDI=0.167).在254 nm光照射下BPS有机桥联结构发生光致断裂反应,表面电荷性质发生由负(–28.20 mV)到正(+22.86 m V)的翻转,BPS纳米粒子通过静电相互作用能够高效装载阿霉素药物,并具有光控药物释放行为.体外释放实验表明,在254 nm光照射下药物的释放率与光照强度和光照时间正相关,可对药物实现定时、定位和定量地精确控制释放,最高药物释放率达到82.9%,该研究为目标分子的控制释放提供了一种新的聚倍半硅氧烷可控释放体系,具有重要应用价值.

Light-controlled release system plays an important role in the stimuli-responsive release application,due to light with its efficient controllability and non-contact.By adjusting the light irradiation of intensity,wavelength,time and location,the release behavior of the target molecule,such as the release rate,location and concentrations,can be performed by spatial and temporal control.Bridged polysilsesquioxanes have a-[A-SiO1.5]n-molecular chain structure(A is an organic group)which show good mechanical properties and biocompatibility.Due to the wide designability and tunability of the A organic group,bridged polysilsesquioxane materials with different properties can be prepared.This kind of hybrid inorganicorganic materials have potential application values on stimulus-responsive release,optical sensors and biological imaging.A novel photoresponsive controlled release system based on this material was designed and prepared in the present study.When target molecules are connected to nanocarriers with photoresponsive groups by a covalent bond,the covalently binding tends to affect the characteristics of the target molecules,and the chemical process of preparing the controlled release system is complex.Therefore,a photoresponsive controlled release system with simple preparation process and guaranteed target molecular characteristics is highly desired to be constructed.In the paper,a bridged silane containing 2-nitrobenzyl group(BS)was successfully prepared.First,2-nitrobenzyl chloroformate was obtained by substitution reaction of 2-nitrobenzyl alcohol and triphosgene.Then,the photoresponsive bridged silane monomer BS was produced from 2-nitrobenzyl chloroformate and bis(trimethoxysilylpropyl)amine.The photoresponsive group 2-nitrobenzyl was covalently connected with the silane through an ester group.The synthesized BS was confirmed by nuclear magnetic resonance spectroscopies(1H NMR,13C NMR,and29Si NMR),FTIR and mass spectrometry.UV-vis spectra showed that BS was photoresponsive under 254 nm light.The characteristic absorption peaks of the BS at 300 and 224 nm obviously changed during the period of irradiation.Furthermore,the maximum photoreaction conversion was 70%at the irradiation time of 70 min.Further,photoresponsive bridged polysilsesquioxane nanoparticles(BPS)were prepared from BS using a sol-gel method.The prepared BPS nanoparticles were characterized by SEM and DLS.The results showed that the nanoparticles had a spherical morphology with an average particle size of 127 nm.The UV-vis spectra of BPS in an aqueous solution irradiated over different time testified the photoresponse property of BPS.More importantly,the surface charge of BPS nanoparticles could be reversed from negative(–28.20 mV)to positive(+22.86 mV)triggered by light.Upon irradiation,the secondary amine groups were exposed on the surface of BPS due to the photocleaved reaction of photosensitive groups.And the further protonation of amine groups in the aqueous solution increased the positive property of the surface of BPS.The properties indicated that the light-triggered charge reversal nanoparticles may be promising candidates for controlled drug release system.Doxorubicin(DOX)as a widely used clinical anticancer drug was used to evaluate the concept of charge reversal.It was easily combined on the BPS nanoparticles by electrostatic interaction.The nanoparticles could efficiently load 14.8wt%of DOX.The strategy to prepare drug-loaded nanocarriers is simple,mild and high efficiency.In vitro release results showed that the loaded DOX release rate had positive correlation with irradiation intensity and irradiation time(254 nm).The release behaviors under different laser power(60,160 and 200 mW/cm2)were performed in PBS buffer(pH 7.4)at 37°C over a period of 16 h.There was no obvious release without light.The loaded DOX release rate increased with the increasing irradiation intensity or irradiation time.The highest release rate was 82.9%under 200 mW/cm2irradiation over16 h.Moreover,no sudden release behavior was found for the drug-loaded nanoparticles occurred within 6 h of irradiation.As a result,the drug release process can be precisely controlled by regulating the irradiation time and intensity.The prepared DOX@BPS drug-loaded nanoparticles exhibited good photoresponsive performance.