基于钙离子驱动的药物负载构建光响应性介孔硅纳米粒的研究

Study of Calcium Ion-driven Drug Loading for Light-responsive Mesoporous Silica Nanoparticles

关键词:  介孔硅纳米粒  药物递送系统  化学治疗  光热治疗

Key words:  mesoporous silica nanoparticles  drug delivery system  chemotherapy  photothermal therapy

摘要:

目的 提高介孔硅纳米粒(mesoporous silicon nanoparticles，MSNs)中药物负载量，并使其具备光响应性等功能。方法 本研究采用模板法制备氨基化的介孔硅纳米粒(MSN-NH₂)，并通过钙离子负载的MSNs(MSN-Ca)诱导化疗药物阿霉素(Doxorubicin，Dox)及光热治疗药物Cypate、二氢卟吩e6(Ce6)的高效负载，制得光响应性载单药或多药的MSNs，并对其理化性质及释药特性进行研究。结果 钙离子可有效负载于MSNs内，并可以诱导Dox、Cypate、Ce6在MSNs孔道内的高效负载，其载药量可分别达到(28.5±1.4)%，(36.8±1.5)%，(36.6±1.7)%；MSN-Ca还可以实现Dox、Cypate、Ce6中的2种或3种药物共同负载。负载Cypate的MSNs具有良好的光热升温效果。载Dox的MSNs具有酸性pH响应性释放Dox的特点。785 nm激光照射可明显增强MSN-Ca-Dox/Cypate的Dox释放，具有光响应性释药的特点。结论 钙离子驱动的药物负载策略在多功能MSNs的构建及其抗肿瘤协同治疗研究中具有重要作用。

Abstract:

OBJECTIVE To improve the drug loading capacity of mesoporous silicon nanoparticles(MSNs) and make it photoresponsive. METHODS This study used the template method to prepare aminated mesoporous silica nanoparticles (MSN-NH₂), and induced the efficient loading of chemotherapeutic agent Doxorubicin(Dox) and the photothermal therapeutic agents(Cypate) and Ce6 within MSNs through the calcium ion-driven drug loading strategy(MSN-Ca), resulting in light-responsive MSNs with single or multiple drugs, and their physical and chemical properties and drug release characteristics had been studied. RESULTS Calcium ions could be effectively loaded into MSNs, and they induced the efficient loading of Dox, Cypate and Ce6 in the pores of the MSNs. The drug loading capacities were (28.5±1.4)%, (36.8±1.5)% and (36.6±1.7)%, respectively. MSN-Ca was capable of co-loading two or three drugs among Dox, Cypate and Ce6. The MSNs loaded with Cypate exhibit a photothermal effect. Dox-loaded MSNs had the characteristic of releasing Dox in response to acidic pH. The Doxorubicin release of light-responsive MSN-Ca-Dox/Cypate was enhanced significantly upon laser irradiation at 785 nm. CONCLUSION This calcium ion-driven drug loading strategy plays an important role in the construction of multifunctional MSNs and expedites the development of anti-tumor synergistic therapy.