| 摘要: | Background
Nanoparticles (NP) and nano-sized medications are increasingly important in the world of medicine due to their abilities to overcome problems related to pharmacokinetics (i.e. absorption, distribution, metabolism and excretion). For example, organic-based NPs can be designed to naturally degrade in the body in order to prevent accumulation and hence prevent toxicity.
Mesoporous silica nanoparticles (MSNs) are a type of inorganic NPs which can be designed to undergo natural degradation in the body. However, several publications, as well as the results from our laboratory, have shown that certain types of MSNs can evade biodegradation. After being injected into mice, certain types of MSNs were found intact in the urine. This is especially puzzling because kidneys normally prevent molecules larger than 6-8 nm from escaping into the urine.
Furthermore, this atypical renal clearance can be found in other types of NPs besides MSNs. Therefore, it is important to identify which physical and chemical characteristics are necessary in order to design renal-clearable NPs, which have the potential to be used clinically. Based on our own data, we have synthesised MSNs that can undergo renal clearance despite being larger than the size limit of 6-8 nm. Moreover, we compare and contrast our results with data from other publications in order to obtain a comprehensive understanding of this phenomenon.
Aims
The main goal of this study is to identify which physico-chemical characteristics are required in order to design NPs that can undergo atypical renal clearance. To fulfil that aim, we have compiled and reviewed various publications which report different types of large NPs that can undergo renal clearance. The different pathways that each type of NPs undergo were identified.
Finally, data from the publications were compared with data from our own laboratory, in which 25 nm rhodamine B isothiocyanate MSNs conjugated with PEG and TA (25 nm RMSN@PEG/TA) had been synthesised and injected into mice. Biodistribution studies of our MSNs were carried out and urine samples were collected to confirm their clearance. Microscopy techniques were used to analyse kidney tissue samples to locate the MSN’s atypical renal clearance at the cellular level.
Results
A total of 12 different types of NPs/nano-delivery systems had been identified from publications which show that they undergo atypical renal clearance, either partial or fully. They are able to cross into the urine either by interacting mainly with the glomerular filtration barrier (GFB), with the proximal convoluted tubules (PCT), or the route is still unknown. 4 important physico-chemical properties are important for renal-clearable NPs: size, charge, composition and surface modifications. Experimental data from our laboratory show that our RMSNs interact with the glomerulus and the mesangium. |
