# Therapeutic Potential of Polymer-Coated Mesoporous Silica Nanoparticles
## 1 Introduction  
With the advent of nanotechnology in biomedical sciences, the application of different materials has increased exponentially to offer solutions for drug delivery and diagnostic challenges [1; 2]. Mesoporous silica nanoparticles (MSNs) are an example of such a material that has been widely used for the development of modern nanoparticulate drug delivery systems targeting various diseases, ranging from cancer to neurodegenerative disorders as well as metabolic disorders such as diabetes. Although discovered in the early 1990s [3], mesoporous silica found their way into the biomedical sciences in 2001 when an mobil composition of matter-41 (MCM-41) material was used for drug loading and the release of ibuprofen [4]. A few years later, mesoporous silica saw a significant boost in this area when the preparation of this material in a nanoparticulate form (i.e., MSNs) began to be reported on. One of the foremost advantages of MSNs are their large surface area and pore volume, which lead to exceptionally high drug loading capacity, but, in turn, may also result in the premature release of the drugs [5; 6]. Premature drug release before reaching the target site hampers the utility of MSNs in targeted therapy. However, the tunable surface chemistry of MSNs allows surface polymer coating,thus providing sustainable and controlled release functions to be integrated by polymers acting as gatekeepers [6; 7]. The optimal biodistribution, biodegradation, and biocompatibility of polymer coated MSNs favour them as a potential type of drug delivery system. Just like any nanocarrier, MSNs absorption and distribution mainly depend on the administration route. For instance, MSNs with a 110-nm size were delivered via intravenous (i.v. ), hypodermic, intramuscular, and oral routes in mice to compare absorption and distribution. After oral administration, MSNs were absorbed after 24 h through the intestine followed by transpose to the liver. Delivery via hypodermic and intramuscular route demonstrated poor absorption whereas after i.v. injection, MSNs were mainly deposited in liver and spleen. However, particle size also played an important role in determining the fate of MSNs in vivo [8]. In a recent study, a decrease in particle size from 142 to 32 nm of MSNs, increased bioavailability regardless of the administration route; intravenous (i.v. ), or intraperitoneal with accumulation in the liver and spleen. The surface chemistry of MSNs played a significant role in excretion, where a positive charge with shielded surface amines demonstrated a higher excretion rate and thus displayed lower liver accumulation compared to cationic and neutral MSNs [9]. The excretion of MSNs was monitored through urine and faeces with no change in kidney structure, suggesting the low toxicity of these nanocarriers [8]. The adsorption, distribution, metabolism, excretion (ADME), and safety of MSNs have been reviewed multiple times in the literature [10; 11; 12; 13]. Since the physical and chemical properties of MSNs can be easily modulated by organic functionalization, the majority of future work is focused on polymer coated MSNs to optimize the properties of these multifunctional hybrid nanocarriers. Though there is a long way to go for MSNs to appear in clinics, some of the parent silica particles have appeared in clinical trials and are presented in Table 1.  
Numerous published reports discuss the applications of MSNs in the biomedical field [14; 15], but literature presenting the significance of polymer coating on MSNs is still somewhat lacking and, therefore, this review will shed light on various polymers utilized for the synthesis of polymer coated MSNs for effective management of their properties under biological conditions (Table 2). Coating of the polymer onto MSN and drug loading are usually performed via two different approaches. In the first approach, pristine MSNs are coated with polymer followed by drug loading, whereas in the second approach, drug loaded MSNs are prepared first, followed by the polymer coating (Figure 1).