功能化二氧化硅纳米材料在肿瘤治疗领域的应用

Biofunctionalized mesoporous silica nanocarriers and the applications in tumor therapy

纳米材料(如脂质体、聚合物胶束、树枝状聚合物)基于其良好的物理化学特性,在药物递送、成像诊断等肿瘤诊疗领域拥有巨大的应用前景.其中,介孔二氧化硅纳米材料(mesoporous silica nanomaterials,MSNs)具有独特的孔径结构、较大的比表面积,并且其粒径大小、形貌结构易于调控,同时结合多种修饰手段,在生物医学领域引起了广泛的关注.MSNs材料功能化修饰后,可作为化学药物、基因、核酸、多肽、蛋白酶等治疗药物载体,在内、外源性刺激触发下,对肿瘤部位进行特异性靶向识别和可控性药物释放,使得肿瘤诊疗一体化成为可能.本文在对MSNs材料独特的物理化学特性进行介绍的基础上,综述了其在现代生物医学中的发展趋势,并展望了其在临床应用中的巨大潜力.

Nanomaterials(such as liposomes,polymer micelles,dendrimers),with their unique physical-chemical properties,have exhibited great potential in tumor diagnosis and treatments.Mesoporous silica nanoparticles(MSNs)are particularly attractive in the drug delivery,imaging diagnosis and other tumor diagnosis fields.Considering MSNs are easily to be functionalized and regulated with designed morphology,surface area,pore sizes,they have attracted widespread attention in biomedicine fields.Various MSNs with morphology,pore diameters,pore arrangements and large surface area have been developed and synthesized for biological applications.Especially,the porous structure of silica nanomaterials provides a large number of pores for loading and releasing various biomolecules and therapeutic drugs,including chemotherapeutic drugs,genes,nucleic acids,peptides,proteases,antibodies,etc.This is also the direct reason why it has become an ideal drug delivery system to overcome defects of some traditional delivery pathways.For better applications,the materials should be functionalized to improve the biocompatibility of MSNs.What’s more,functionalized MSNs are usually modified with organic,inorganic molecules,polymers and other metal nanoparticles to provide their ability to load and release drug molecules on-demand.Furthermore,via optimizations on both loading mode and reaction conditions,the drug specificity,treatment performance,in vivo solubility or stability can be improved.In addition,the side effects caused by adverse pharmacokinetics could also be decreased.Thereafter,MSNs can trigger the targeted recognition and controlled release for tumor diagnosis and treatment.After entering the organism,the accurate and large-scale delivery of drugs into tumor tissue remains an urgent problem.By means of passive and active targeting,MSNs can be delivered to the tumor sites so as to improve the therapeutic efficiency.More importantly,the intelligent delivery of drugs would be an ideal strategy to release therapeutic drugs as needed after internal/external stimulation.With this strategy,the early release of drugs before delivery to the target tissue can be avoided.Therefore,the utilization efficiency of drugs can be greatly improved and the potential toxic and side effects of drugs on normal cells could be readily reduced.In recent years,MSNs have obtained rapid developments in diagnostic biological imaging,tissue engineering,cancer treatment,vaccine development,biomaterial application and diagnosis.Nevertheless,some practical problems are still urgent to be solved to achieve the clinical application of silica nanomaterials.For example,the large-scale production of silica nanomaterials with controllable size and colloidal stability is an important issue to ensure scalability and reproducibility of this method.The biological problems involved in nano carrier administration,such as the establishment of specific modification methods and the study of distribution in organisms should also be examined.In this review,based on the introduction of physical and chemical properties of mesoporous silica nanoparticles,the various synthesis methods of silica nanomaterials are summarized.Thereafter,the applications and developments of different MSNs in biological drug delivery technology are illustrated.Finally,the safe and degradable metabolic pathways of MSNs in vivo are reviewed,which is looking forward to great potential in clinical applications.